session D: miscellanea

Annals of Oncology 18 (Supplement 11): xi56–xi88, 2007

doi:10.1093/annonc/mdm426session D: miscellanea

D1 SECOND-LINE CHEMOTHERAPY FOR METASTATIC/RECURRENT HEAD AND NECK CANCER

D. Ferrari1, C. Codeca1, S. Caldiera1, S. Zonato1, A. Luciani1, J. Fiore1,M. Cossu-Rocca2, E. Verri2, P. Foa1

U.O. Oncologia Medica Ospedale San Paolo, Milano1; U.O. Oncologia MedicaIstituto Europeo di Oncologia, Milano2

Background: Squamocellular carcinoma of the head and neck (HNSCC) accounts for5% of all cancers. First line therapy includes surgery, chemotherapy (CT) andradiotherapy (RT), depending on the site and stage of primary tumour. Patients (pts)with recurrent or metastatic HNSCC (R/M HNSCC) have a poor prognosis and in thissetting few drugs have demonstrated to be safe and effective. The purpose of this phaseII trial was to investigate safety and activity of the carboplatin and paclitaxelcombination . Tumour response, time to progression (TTP) overall survival (OS) andtoxicity profile were evaluated.

Methods: Pts with R/M HNSCC previously treated with induction CT (cisplatin100mg/m2 plus 5-FU 1000mg/m2 continuous infusion over 96hours every 3 weeks)followed by concomitant chemoradiotherapy were studied. Treatment consisted ofCarboplatin AUC 5 and Paclitaxel 175 mg/m2 intravenously every 3 weeks.Darbepoetin alpha and G-CSF were allowed for support in case of anemia (Hb<10g/dL) and neutropenia (neutrophils<1000/mmc). Pts were evaluated for toxicity andresponse after 4 courses of CT.

Results: A total of 22 pts (15 locoregional and 7 metastatic disease) were enrolled(median age 59 yrs, ECOG PS 0-1). Site of primary tumour included oral cavity(45.5%), nasal cavity (4.5%), nasopharynx (31.8%), larynx (13.7%) and hypophanrynx(4.5%). All but one patient, who refused CT after the first cycle, were evaluated forresponse and treatment-related toxicity; intention-to-treat analysis was performed.One complete and 5 partial responses were observed (27.3% overall response rate).Stable disease was seen in 6 pts (27.3%) and progression was observed in 10 pts(45.4%), TTP was 2.3 months. Median OS was 9 months. Toxicity was mild: G2-3neutropenia occurred in 4 pts (18%), while only one patient developed febrileneutropenia. Grade 2-3 anemia occurred in 5 patients (22.7%), and 1 patient had G3thrombocytopenia (4.5%). Paclitaxel-associated neuropathy (G1-2) was seen in 9patients (40.9%).

Conclusions: The association of paclitaxel and carboplatin was effective as second-linetreatment in R/M HNSCC. The overall response rate and survival were comparableto those achieved with commonly used cisplatin/5-fluorouracil regimen, but toxicitywas mild and manageable.

D2 HOME PARENTERAL NUTRITION: EVALUATION OFPROGNOSTIC FACTORS

F. Rahimi, E. Agnello, M. Scigliano, T. Monge, C. Finocchiaro, L. Fanchini1,O. Bertetto1, A. Evangelista2, G. Ciccone2, A. PalmoClinical Nutrition Unit ASO S. G. Battista Turin, 1Medical Oncology-COES ASOS.G. Battista Turin1, 2Cancer Epidemiology Unit ASO S.G. Battista Turin1

Background: The indication to Home Parenteral Nutrition (HPN) in advanced cancerpatients (ACP) still remains a controversial issue. In this setting randomised controlledstudies are hardly feasible for ethical reasons; results of large series of pts included andtreated with similar methods may offer a more detailed background to establishinclusion criteria.

Methods: A multicentre prospective observational study on HPN in ACP was fundedin years 2001-2006 by the Health Council of the Piedmont Region. The protocolestablished inclusion criteria (oral intake <75% BEE and contraindication orintolerance to enteral nutrition, life expectancy >60 days, Karnofsky Index KI>50,control or absence of pain, absence of severe functional alterations), nutritionalassessment, intervention and monitoring, cause of ceasing. Competing risk modelswere used to compute risk of death (DT) or resumed oral feeding.(ROF).

Results: In 6 years n 688 pts were included in the study (stomach 23%, colon rectum20%, pancreas 16%, urogenitals 9% head and neck 6%, lung 5%, oesophagus 3%,others 18%). At 120-day follow-up, cumulative incidence rates were 57% for DT and11% for ROF. In model adjusted for age and sex, palliative chemoterapy (CT) wasassociated with decreased risk for DT (HR,0.58; 95% CI, 0.48-0.71) and with increasedrisk for ROF (HR,2.34; 95% CI, 1.44-3.82). In contrast, presence of MTS was relatedwith increased risk for DT(HR,1.56; 95% CI,1.24-1.96) and with decreased risk forROF ( HR,0.45; 95% CI, 0.29-0.70). KI >60 was associated with decreased risk for DT(HR,0.77 vs KI£60; 95% CI, 0.64-0.93);otherwise, KI was not significantly related toincident ROF.

Discussion: The identification of prognostic factors (KI>60, absence of MTS and CT)in ACP is of considerable importance for the clinical management. CT and absence ofMTS, but not KI are predictors of weaning from HPN and total oral rehabilitation, in

a low but relevant percentage of patients. In these subjects HPN may represent anindispensable part of the therapy.

D3 RENAL TOXICITY AND OSTEONECROSIS OF THE JAWS INPATIENTS WITH BONE METASTASES RECEIVINGBISPHOSPHONATES: A RETROSPECTIVE ANALYSIS

1Maria Bonomi, 1Rolando Nortilli, 1Annamaria Molino, 1Teodoro Sava,1Antonio Santo, 1Alessia Caldara, 1Gian Luigi Cetto1Dipartimento di Oncologia Medica, Universita degli Studi di Verona, Italy

Background: Bisphosphonates (BP) have shown efficacy in the treatment of bonemetastases from multiple myeloma and a wide range of solid tumours. Some patients,most of all long term treated, can experience renal toxicity and osteonecrosis of thejaws.

Matherials and methods: Three hundred ninety nine patients’ data who received iv BPfor bone metastases were reviewed. Their serum creatinine levels were checked all overthe treatment period to assess their renal function. ONJ signs and symptoms, reportedin their medical files, were looked for. Other possible risk factors for both renal toxicity(such as NSAIDs and chemotherapy) and ONJ (corticosteroids, previous dentalextractions. . .) were also considered.

Results: The median treatment period was of 14 months (1-119); 108 patients receivedBP for more than one year and other 112 for longer than two years. Sixteen out of 398patients (4%) experienced renal toxicity after a median period of BP of 24 months.Eight of them (50%) had been treated for more than two years. All but one had othernephrotoxic risk factors. Ten patients (2,5%) were diagnosed ONJ after a median timeof 39 months of therapy with BP; only three of them had been treated less than 24months. Two experienced both ONJ and renal toxicity.

breast prostate lung kidney other total

Patients 238 46 39 15 60 398Nephrotoxicity (%) 7 (2,9) 3 (6,5) - 1 (6,7) 5 (8,3) 16 (4)ONJ (%) 7 (2,9) 1 (2,2) - - 2 (3,3) 10 (2,5)

Conclusions: In this retrospective analysis BP proved to be safe in most of the 398patients considering the relatively low incidence of both renal toxicity and ONJ.Nevertheless prevention and early detection are still the ‘‘first line’’ therapy to furtherdecrease the occurrence of these events.

D4 THE UTILITY OF FISH TECHNOLOGY AS DIAGNOSTIC TOOL INMYELODYSPLASTIC SYNDROMES

Pisano M*, De Filippi A*, Greco L+, Vergara D#, Valacca A** and Leo G**U.O. Molecular Biology and Experimental Oncology (P. O. ‘‘V. Fazzi’’-AUSL LE),#National Nanotechnology Laboratory, CNR-INFM, University of Salento, Lecce,Italy, +Department of Biological and Environmental Science and Technologies,University of Salento, Italy, ** Department of Ematology, ‘‘Vito Fazzi’’ Hospital,Lecce, Italy

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone marrowdisorders characterized by both bone marrow failure and cytopenia. The aim of thiswork is to evaluate the utility of fluorescence in situ hybridization (FISH) technology todetect chromosome abnormalities in MDS patients and clarify their involvement in theonset of the disease. We examined 125 adult patients distributed in three age classes(30-50; 51-70; 71-90). Blood marrow aspirate and/or peripheral blood were analyzedby FISH by using fluorescent probes for the regions 5q33-34, 7q31, 20q12 and 8p11.1-q11.1. Chromosomal rearrangements were identified in 20 patients out of 125 (16%).The majority of rearrangements were found in patients over 50 years with a malepredominance (male/female ratio 2:1) in particular in the age range 71-90 (65%).Considering single rearrangements, the most frequently observed aberration was thedeletion of long arm of chromosome 20 del(20q). In total, it was present in 65% of allrearrangements and associated with a good prognosis. In addition, trisomy 8 was foundin five patients (25%), four men and a woman. Whereas, aberrations of chromosomes5 and 7 were detected but in low incidence. The percentage of incidence of del(20q) was30% in men aged 71-90 years and 15% in me aged 51-70 years. The same abnormalitywas present in 15% of women aged 71-90 years and 5% in women aged 30-50 years. Bycomparing the initial diagnostic suspect with the definitive diagnosis, we found that thediagnosis of MDS was confirmed in 32 patients and in 8 of these patients we identifiedchromosomal rearrangements (del(20q) in 5 specimens, 8+ in 3 specimens). Ourresults want to underline the importance of FISH technology as diagnosis tool forMDS. Overall, we have confirmed that MDS usually occur over the 5th decade andshown the major prevalence of del(20q) in our population.

se

ssio

nD

ª 2007 European Society for Medical Oncology

by guest on July 29, 2013http://annonc.oxfordjournals.org/

Dow

nloaded from

http://annonc.oxfordjournals.org/

D5 TAXANES, CISPLATIN AND FLUOURACIL FOR RELAPSED ORUNRESECTABLE NODAL METASTASES FROM SQUAMOUS CELLCARCINOMA OF THE PENIS. PRELIMINARY RESULTS

Giorgio Pizzocaro* and Angelo Milani***Consultant Urologic Clinic II, Milan University and **Urologic Unit, IstitutoNazionale Tumori (INT) Milan, Italy

Patients with relapsed or fixed inguino-pelvic node metastases from squamous cellcarcinoma (SCC) of the penis usually have a poor prognosis. As SCC of the penis isresponsive to the same chemotherapy regimens as SCC of the head and neck(Pizzocaro:Genitourinary Oncology,pg.827-83, LWW,2006) we introduced taxanes inthe cisplatin-5FU (PF) treatment for these patients starting in 2004.

Between 2004 and 2006, 46 consecutive patients with SCC of the penis have beentreated at the Urologic Unit of INT in Milan. Seven patients had unresectable orrelapsed nodal metastases. Six of them were treated with taxol 120mg/m2 or taxotere 75mg/m2 before PF (CDDP 100mg/m2 day 1 followed by 4 days continuous intra venousinfusion of 5FU 1000) : 3 patients had fixed and/or ulcerated inguinal nodes, and theother 3 had recurrent nodal metastases. The free interval between lymph nodedissection and relapse was: 12, 20 and 30 months. Conservative penile surgery waspossible in the one patient who had penile biopsy before starting chemotherapy and heachieved a complete remission with chemotherapy both in the primary tumor and inlymphnode metastases. The other 5 patients had penile amputation. Four courses werescheduled every 3 weeks, with first evaluation after the first 2 courses.

One patient did not respond and died within 3 months. One patient had an 80%partial remission and refused to continue therapy after 2 courses. He underwentsurgery and is alive disease-free 33 months after starting chemotherapy. The other4 patients had a clinical complete remission pathologically documented. They are alivecontinuously disease free from 13 to 34 months after starting chemotherapy. Toxicitywas mild: only one patient had myelotoxicity (WBC 1.8 with 30% neutrophyls) andanother one had modest renaltoxicity (serum creatinine 1.8).

TPF chemotherapy in this small series of patients demonstrated significant activityin unresectable relapsed nodal metastases from SCC of the penis with moderatetoxicity.

D6 ASSESSMENT OF LEFT VENTRICULAR SYSTOLICDYSFUNCTION BY TISSUE DOPPLER IMAGING TO DETECTSUBCLINICAL CARDIOMYOPATHY EARLY AFTER ANTHRACYCLINETHERAPY

Marzia Lotrionte, MD, Giovanni Palazzoni, MD*, Rosaria Natali, MD,Giuseppe Biondi-Zoccai, MD,� Gianluca Comerci, MD, Marinica Savino, MD,and Francesco Loperfido, MD

Cardiovascular Department, and *Oncology Department, Catholic University,Rome; �Division of Cardiology, University of Turin

Background: Anthracycline (ANT) chemotherapy for breast cancer, while associatedwith high response rates, is fraught by risks of irreversible cardiotoxicity.Unfortunately, means to detect such cardiotoxicity early on and at a sublinical stage arelacking. We thus evaluated the role of systolic tissue Doppler imaging (TDI) inappraising post-chemotherapy left ventricular (LV) remodelling.

Methods: Patients undergoing ANT-chemotherapy for breast cancer were enrolled,and underwent baseline and >6-months echocardiography (standard and TDI).According to the pattern of LV-TDI systolic remodelling from baseline to follow-up,patients were stratified in: group 1 (no LV-TDI worsening), group 2 (minor LV-TDIworsening), and group 3 (major LV-TDI worsening).

Results: Fifty-six patients were included (follow-up 9±6 months). At baseline, nonehad abnormal LV ejection fraction (LVEF), LV-TDI systolic dysfunction or NYHA>1.Follow-up analysis showed significant deterioration in LVEF, end-diastolic diameter(EDD) end-systolic diameter (ESD), and TDI-systolic parameters (all p<0.05).Specifically, 29 (51.8%) patients showed no adverse LV-TDI systolic remodelling, while17(30.4%) were in group 2, and 10(17.9%) in group 3. All groups shared similarconditions at baseline, patients with adverse LV-TDI remodelling had significantincreases in EDD and ESV, as well as a significantly decreased LVEF (all p<0.05). Nopatient in group 1 had abnormal LVEF at follow-up, while 1 patient in group 2 and 2patients in group 3 had abnormal LVEF (p<0.05).

Conclusions: Subclinical systolic dysfunction occurs in almost 50% of patients earlyafter chemotherapy for breast cancer, with a more adverse by LV-TDI remodellingimplying a more pronounced deterioration of standard echocardiographic parameters.

D7 INDUCTION CHEMOTHERAPY WITH DOCETAXEL FOLLOWEDBY CONCOMITANT CHEMORADIOTHERAPY WITH DOCETAXEL INHEAD AND NECK SQUAMOUS CANCER: PRELIMINARY DATA OF AFEASIBILITY STUDY

Bergaglio Marina, Grimaldi Andrea*, Galbusera Valentina, Grillo Ruggieri Filippo*,Scasso Felice^, Moratti Giuseppe^, Dellepiane Massimo§, Bavazzano Maurizio§,Ghio Riccardo’’ Mencoboni ManlioOncology Unit, Villa Scassi Hospital, Genoa, Italy

Introduction: Concomitant chemoradiotherapy was shown to be feasible in patientswith nonsurgical squamous cell carcinoma of the head and neck (SCC-HN). Taxoterehas shown in vitro and in vivo radiosensitizing properties, synergistic activity withcisplatin, and cytotoxic activity against SCC-HN. Thus, we are testing the feasibilityand antitumoral activity of an induction chemoradiotherapy program that includestaxotere.

Patients and methods: This is a preliminary report of our phase II prospective nonrandomized trial. Until now ten patients with stage IV or unresectable SCC-HNhave been enrolled. Enrollment of 29 patients is planned. Medium PS was 1(0-1);Medium age was 59 (31-68). None had previously received chemotherapy orradiotherapy. Feasibility and toxicity were primary end point. Response rate issecondary end point.

The treatment plan consisted of cisplatin 70 mg/m2 and docetaxel 70 mg/m2 onday 1 and 21. On day 42 radiotherapy was started: Radiation was administered during6 weeks, with conventional fractionation up to 60 Gy. Weekly docetaxel at the doseof 33 mg/m2 was administered together with radiotherapy. Toxicities were assesedaccording to NCI-CTC criteria at every chemotherapy administration. Responseevaluation was assessed according to RECIST criteria.

Results: Toxicity was mild to moderate in any case. All the patients had the plannednumber of chemotherapy courses in the concomitant phase and all but one received theplanned radiation dose. Toxicities were present only after the IV week of concomitanttreatment. We recorded mucositis of grade 3 in 6 patients and of grade 2 in 2 patient;grade 3 anemia was recorded in 1 patient, grade 2 anemia in 2 patients. Leukopenia ofgrade 1 was recorded in 1 patient. Cutaneous grade 1 toxicities was recorded in 1patients, grade 2 in 5 patients, grade 3 in 3 patients. At present only 4 patient isevaluable for response: they achieved complete resonse.

Conclusions: From our preliminary data, this treatment seems feasible and effective;but it is necessary to end the enrollment and data collection to answer this question.

D8 STUDY ONJ007 FOR THE PREVENTION, PHARMACOLOGICALAND NUTRITIONAL TREATMENT OF ONJ IN PATIENT TREATEDWITH BISPOSPHONATES FOR BONE METASTASIS

Pellegrini M, Marchetti S, Melosi A, Battistoni M, Tanganelli L, Cirigliano G, Loni L,Bronner L, Barsanti G*U.O. Medicina ad indirizzo Oncologico USL2, Ospedale Campo di Marte, Lucca

Bisphosphonates (BSF) are the therapeutic standard for treatment of patients withmetastatic bone disease. The development of complications like osteonecrosis of themaxilla and mandible (ONJ) that seem associated with the use of BSF has carrieda reduction of the indications to the treatment with BSF due to worsening of patientquality of life. Prevention of ONJ is important to avoid the onset of this pathology.Selection of the patients is the first phase of the prevention with a multidisciplinaryapproach of the oncologic patient treated with Bisphosphonates. We designeda observational study (ONJ007) to evaluate effectiveness of the prevention in ONJdevelopment in patients candidates or already in treatment with BSF for bonelocalizations from solid or haematological neoplasia and/or osteoporosis; moreover,our study comprises a protocol for the treatment of ONJ and its effectiveness has beenevaluated. 400 patients received BSF since January 2003 to December 2006 for bonemetastasis and/or osteoporosis in our day hospital. Among patients treated withintravenous Bisphosphonates, 9 developed ONJ. We observed also that among patientswith ONJ, 2 developed IRC, 2 diabetes, 2 increase of PTH value, 5 abscessed teeth andoral ulcer, 2 patients developed ONJ after dental extraction. Therefore considering thehigh incidence of ONJ, all patients treated with BSF since 1 January 2007, entered inour protocol ONJ007. Before starting BSF, patients underwent specific control ofbuccal cavity; all performed onco-odontostomatological and psychologicalexamination, haematochemical exams and check to detect potential risk factors:increase of PTH value, diabetes, hypocalcemia, concomitant antiangiogenetic, Taxanesand hormonal therapy. Patients with diagnosis of ONJ were given IDAS and VAS scaleand were subdivided in 3 classes based on symptoms, signs of phlogosis and boneexposure. All patients performed panoramic radiography and SPECT/CT. Moreover,nutrition advices and recipes to improve nutrition were given to patients showingintense pain of the jaw, chewing and speech problems.

D9 COMBINED SURGERY AND POST-OPERATIVE RADIOTHERAPYOR CHEMORADIOTHERAPY FOR LOCALLY ADVANCED TONGUECANCER

C. Codeca1, F. Chiesa2, L. Calabrese2, B. Jereczek-Fossa3, A. Maccari4,G. Felisati4, J. Fiore1, S. Oldani1, D. Ferrari1, P. Foa1

U.O. Oncologia Medica Ospedale San Paolo, Milano1; Divisione di ChirurgiaCervico-facciale Istituto Europeo di Oncologia, Milano2, U.O. di RadioterapiaIstituto Europeo di Oncologia, Milano3, U.O. Otorinolaringoiatria Ospedale SanPaolo, Milano4

Background: Treatment options for locally advanced tongue squamocellularcarcinoma (SCC) include surgery alone, radiotherapy alone, or multimodalitytreatment. These highly aggressive tumors are best treated by partial glossectomy inorder to save organ function and postoperative radiotherapy (RT). When positivemargins and/or extracapsular nodal extension are found, postoperative

Volume 18 | Supplement 11 | October 2007 doi:10.1093/annonc/mdm426 | xi57

Annals of Oncology session D by guest on July 29, 2013

http://annonc.oxfordjournals.org/D

ownloaded from


chemoradiotherapy (CRT) is warranted. We report on our experience with thisapproach.

Methods: A total of 20 patients (pts) with primary tongue SCC were treated withsurgery and postoperative RT. All pts underwent partial, hemi-, or subtotalglossectomy; 16 pts (80%) underwent ipsilateral radical or modified radical neckdissection. Ten pts received postoperative RT alone (median dose 6000 cGy) while 10pts received postoperative CRT consisting of RT and Cisplatin 100 mg/m2 days 1-22-43. Stage distribution was as follows: stage III, 5; stage IV, 15. Median follow-up is 23months.

Results: For the entire group of pts, the actuarial 2-year locoregional control rate was80%; the same rate was recorded for both stage III and IV disease. The actuarial 2-yearoverall survival rate was 70%. There was one local failure among 10 pts with negativemargins (local control 95%) and 3 among pts with positive margins (local control85%). Four pts developed distant metastases, 2 with negative and 2 with positivemargins. Postoperative treatment was well tolerated. Three pts treated by RT and 4 ptstreated by CRT experienced grade 3 oral mucositis. Late major complications of RTand CRT included 3/20 pts requiring permanent G-tubes and/or tracheostomy toprevent aspiration.

Conclusions: Surgery plus postoperative RT is an intensive treatment for SCC of thetongue which offers high locoregional control rate in patients with negative margins.Postoperative CRT can be safely administered to pts with positive margins and/orextracapsular nodal extension achieving satisfactory results in terms of bothlocoregional control and distant failure.

D10 CISPLATIN BASED CHEMOTHERAPY FOR RECURRENT ORMETASTATIC HEAD AND NECK CANCER IN THE ELDERLY

Luciani A, Cavina R, Cereda S, Galeassi A, Ascione G, Marussi D, Codeca C,Foa PU.O. Oncologia Medica Ospedale S. Paolo-Milano, Istituto Clinico Humanitas,IRCCS-Rozzano, Istituto Scientifico S. Raffaele-Milano, Policlinico S. Donato-Milano

Background: Elderly patients (pts) with recurrent or metastatic squamous cellcarcinoma of the head and neck (SCCHN) are generally undertreated in clinicalpractice and underrepresented in clinical trials.We performed a multicentreretrospective analysis on the use of Cisplatin based chemotherapy (CT) for elderly ptswith advanced or recurrent head and neck cancer, with the exception ofnasopharyngeal cancers.

Patients and methods: Pts 67 years old or more were considered.PS,number andseverity of comorbidities using CIRS-G score and index, polypharmacy were rated.Foreach pt number of cycles, response rate, previous CT, radiotherapy and surgery wererecorded. Median survival was calculated. Cox proportional hazard model was used toidentify factors predicting prognosis.

Results: 67 elderly pts (mean age 73, 67-85 years), 19% female and 81% male wereconsidered. 79% (53/67 pts) had PS 0-1. Mean drugs and comorbidities were 2 (0-9)and 1,52 (0-5). Correlations between CIRS-G score and index was 66% (alpha). 97%(65/67 pts) had squamocellular histology,and 51% (34/67) grade 3. 57% (38/67 pts)were nodal status N2. Mean n of cycles was 5 (1-9, SD 1,75). Grade 3-4 hematologicaltoxicity occurred in 24% (16/67), non hematological toxicity in 39% (26/67) of pts.The most frequent toxicities were mucositis grade 3 (18%, 12/67), fatigue grade 2 (5/67,7%). 31% (21/67 pts) had dose reduction and 16% (11/67 pts) had premature CTdiscontinuation due to toxicity. 37% and 43% had radiotherapy and surgery before,24% had CT in the past.Median overall survival was 10 months (8,56-11,44, CI 95%).In the cox proportional model two variables, CIRS-G score (Hazard ratio 1,254, 95%CI 1,066-1,474) and non haematological toxicity (HR 3.546, 95% CI 0.978-12.738),were significantly associated with survival (p 0.032 and 0.05 respectively).

Conclusions: Proper selection of pts and of treatment regimen is crucial for improvingoutcome in elderly subjects with recurrent or metastatic SCCHN.

D11 RESULTS OF A MONOINSTITUTIONAL SURVEILLANCEPROGRAM IMPROVING OUTCOME OF OSTEONECROSIS OF THEJAWS (ONJ) IN CANCER PATIENTS (PTS) TREATED WITHBISPHOSPHONATES (B)

Nicla La Verde, Mariastella Dimaiuta, Cristina Mantica, Stefano Cobelli, PaolaSburlati, Karen Borgonovo, Celso Bianchi, Annalisa Bramati, Dorian Mihali,Gabriella FarinaDepartment of Oncology, Azienda Ospedaliera Fatebenefratelli e Oftalmico -Milano

Background: B, that reduce skeletal events in pts with bone metastases, have beenassociated with increased risk of ONJ. An appropriate prevention and managementstrategy must be identified to reduce ONJ injures.

Patients and methods: In pts receiving pamidronate (P) 90 mgmonthly or zoledronate(Z) 4 mg monthly we retrospectively evaluated the advantage of a preventive protocolbased on clinical oral cavity examination and physicians and pts education.

Results: From October 2003 to October 2006, 154 consecutive pts were treated with B;95 females, 59 males; primary tumors: 66 breast, 28 prostate, 26 lung, 9 myeloma, 4

NHL, 21 other. In June 2005 we started the monitoring program on our pts. ONJ wasdiagnosed in 15/154 (9.7 %) pts, 8 before and 7 after June 2005; all pts were treated withZ (total 2987 courses, range 8-43; median courses/pt 19.4) and 4 pts pretreated alsowith P (total 124 courses, range 12-43, median courses/pt 31).

Tumors: 7 breast, 1 kidney, 2 lung, 1 head-neck, 1 thyroid, 1 NHL, 1 prostate, 1sarcoma.

Concomitant therapies: 14 pts chemotherapy; 7 hormonotherapy; 2 head-neckradiotherapy; 5 steroids. Significant anamnesis: 9 recent dentoalveolar procedures, 4diabetes.

First symptoms: Multiple recurrent alveolar abscesses 9, pain 3, dental mobility 1,paresthesia of the lower lip 1, exposed bone 1. Main treatments were: antibiotics andantifungals 11, curettages 3, surgical resections 4 (1 partial maxillectomy, complicatedby septic shock and oronasal communication, 2 partial mandibulectomies, 1 segmentalmandibular resection). These last 4 pts, that had the worst prognosis, were diagnosedbefore starting the monitoring program. 7 new ONJ cases, diagnosed after June 2005,were successfully treated with a conservative approach.

Conclusion: ONJ is a serious and debilitating condition, occurring in 9.7 % of ptstreated with B. A monitoring program based on non-aggressive surgical measures andpatients and physicians education improves the outcome of these pts.

D12 CORRELATION BETWEEN MUCOSITIS AND RESPONSE TOSUNITINIB

A. M. Grimaldi1 E. Perrotta1, A. La Mura1, G. Ragone1, M. Montano1, G. Aurilio1,M. Otero1, C. Stavolo1, T. Guida1, and G. CartenI1

A.O.R.N. A. Cardarelli, Division of Oncology, Napoli

Background: Sunitinib Malate (SM), is a tyrosine kinase inhibitor indicated in thetreatment of metastatic Renal-Cell Carcinoma (mRCC). We treated 51 patients withmRCC with SM and evaluated the relationship between side effects and Clinical Benefit(PR plus SD).

Methods: Pts were clinically evaluated and Haematological and biochemicalparameters were measured before every cycle of SM-treatment and. We consideredonly pts after 2 cycles of therapy or in PD in the same period.

Results: On 37 pts evaluable 19 pts (51%) had a PR, 14 pts (38%) had a SD and 4 pts(11%) had a PD. Mild mucositis resulted the most frequent side effect, because 24 pts(65%) experienced this symptom. On 33 pts (89%) with Clinical Benefit (SD + PD) 22pts (60%) experienced mucositis in different grades: grade 1 was found in 6 pts (28%),grade 2 in 14 pts (63%) and grade 3 in only (9%). No grade 4 mucositis was found inour experience.

13 pts (35%) did not experience mucositis and 11 pts (30%) had Clinical Benefit: 7pts (19%) had PR and 4 pts (11%) had SD.

Conclusions: In our experience, the correlation between mucositis and Response toSM-treatment appears clear. More than 66% of patients who had Clinical Benefit,experienced mucositis. This side effect was generally well tolerated (pts with G.1 + G.2mucositis = 91%) and no grade 4 mucositis was found.

More data are needed to confirm our analysis.

D13 ALPHA-DYSTROGLYCAN EXPRESSION AND SURVIVAL INRENAL CELL CANCER PATIENTS

Alessandro Sgambato1, Andrea Camerini1-2, Filomena De Luca3, GiannicolaGenovese1, Loredana Lo Giudice1, Chiara Valsuani2, Gianna Tartarelli2, SaraDonati2, Cheti Puccetti2, Olimpia Siclari2, Achille Cittadini1, Domenico Amoroso2

1Centro di Ricerche Oncologiche ‘‘Giovanni XXIII’’ - Istituto di PatologiaGenerale, Universita Cattolica del Sacro Cuore, Rome, Italy 2Istituto ToscanoTumori, U.O.C. Oncologia Medica and 3U.O.C. Anatomia Patologica OspedaleVersilia, AUSL 12 - Viareggio, Italy

Background: The dystroglycan (DG) complex is a transmembrane glycoproteincomposed by two sub-units (alpha and beta) that forms a continuous link from theextracellular matrix to the actin cytoskeleton. Deregulated expression of DG has beenreported in a variety of human malignancies and related to tumor differentiation,aggressiveness and survival in breast cancer.

Methods: The expression of alpha-subunit of DG was evaluated by immunostaining ina series of 125 renal cell carcinomas (RCCs) and its relation with clinical-pathlogicalparameters, disease progression and cancer-specific survival was evaluated.

Results: The median follow-up is 19 months (range 1-96). We found that alpha-DGexpression was lost in a significant fraction of tumors (66%) with 18% being the meanpercentage of positive cells (median = 0; range = 0-80%). Loss of alpha-DG stainingcorrelated with higher tumor grade (p = 0.039) but not with tumor stage or size.Recurrence (p = 0.014) and death (p = 0.041) from RCCs were significantly morefrequent in patients whose tumors displayed reduced staining for DG compared withpatients whose tumors were positive for alpha-DG expression. Kaplan-Meier analysisshowed a significant separation between high vs low alpha-DG expression for bothdisease-free (p = 0.0094) and overall (p = 0.0023) survival. At multivariate analysis, lossof alpha-DG expression was the only independent risk predictor for recurrence (HR =6.509, p = 0.0012) and death (HR = 4.701, p = 0.012) from RCCs when tumor size,tumor grade and stage were included in the model.

xi58 | session D: miscellanea Volume 18 | Supplement 11 | October 2007

session D Annals of Oncology


Dow

nloaded from


Conclusions: our findings demonstrate that loss of alpha-DG expression,corresponding to loss a functional DG complex, is a frequent event in human renaltumorigenesis and is associated with an aggressive phenotype of the disease and a worseprognosis. We suggest that evaluation of DG expression has the potential to offerimportant prognostic information and warrant further studies to better understand therole(s) of DG in term of renal cancer development and as a new prognostic marker forRCC patients.

D14 EXOSOMES FACTORY: A NEW STRATEGY FOR ANTITUMOURVACCINES

Napoletano C1, Spinelli GP2, Pauselli S1, Bellati F3, Pinto D1, Landi R1, Rughetti A1,Tomao F3, Benedetti Panici P3, Tomao S2, Nuti M1

1Department of Experimental Medicine, ‘‘Sapienza’’ University, Rome, Italy;2Department of Experimental Medicine, University of Rome ‘‘Sapienza’’-PoloPontino-Italy; 3 Institute of Gynaecology, Perinatology and Child Health,‘‘La Sapienza’’ University, Rome, Italy

Several cell types, including Antigen Presenting Cells (APCs) and tumour cells, secretemicrovesicles that are organelles of 60-300 nm sizes, actively secreted throughexocytosis. Microvesicles from APCs, such as B-lymphocytes and dendritic cells (DCs),contain HLA class I, HLA class II and costimulatory molecules and have been shown tostimulate antigen specific CD4+ and CD8+ T cell responses. Moreover tumour cell-derived microvesicles can elicit immune responses through cross-presentation oftumour antigens via DCs. Here we describe the development of an ‘‘exosome factory’’,an in vitro system for large-scale production of predefined tumour cell-freeimmunogens for immunotherapy. Lymphoblastoid cell line DG-75 (EBV-, HLAI-A2+) was engineered to express Erb-B2 tumour associated antigen. The producedmicrovesicles were purified and biochemically characterized. Immunogenicity ofErb-B2 microvesicles is currently under investigation in epithelial cancer patients(HLA-A2+ and Erb-B2+). Preliminary data suggest that CD8+ T cells derived frompatients were able to produce IFNg after stimulation with Erb-B2-microvesicles pulsedDCs. Moreover Trastuzumab added to Erb-B2 microvesicles appeared to modulatethe immunogenicity of DCs. This novel approach has several advantages i.e. thepossibility to choose selected regions of a TAA and/or combination of these withno restriction of patient haplotype. In addition, the microvesicles can be obtained inlarge-scale production in GMP conditions for clinical application.

D15 OVEREXPRESSION OF P53 PROTEIN PREDICTS COMPLETERESPONSE TO CHEMORADIATION THERAPY IN T2-T4 BLADDERCANCER: TEN YEARS FOLLOW UP

M. Brighenti, N. Naldi, C. Caminiti, D. Potenzoni, M. Fumagalli, P. Crafa,S. Buti, R. PassalacquaDivision of Medical Oncology, Azienda Istituti Ospitalieri Cremona

Purpose: To investigate whether p53, bcl-2, c-erbB-2 protein expression and Ki67antigen predict the achievement of a complete response (CR) to neoadjuvantchemoradiotherapy in patients (pts) with T2-T4 bladder cancer (BC).

Methods: Since March 1994, 75 pts with muscle invasive bladder cancer were treated inthe same institution with a bladder sparing approach including an initial transurethralresection (TUR) and 3 cycles of chemotherapy (cisplatin 20 mg/sqm/die and 5-fluorouracil 200 mg/sqm/die x 5 days, every 3 weeks) alternating with pelvicradiotherapy (40 Gy in 4 weeks). Pts were then evaluated with cystoscopy, multiplebiopsies and CT scan. Pts with residual disease were considered incomplete responders(IR) and underwent to immediate cystectomy. Biopsy proven complete responderswere treated with two additional CT cycles plus a bladder RT boost with 24-28 Gy. For55 pts the paraffin embedded blocks of the primary tumors were collected and Ki67proliferation antigen, p53, bcl-2 and c-erbB-2 protein expression wereimmunohistochemically evaluated in a blind fashion. For each parameter, the receiver-operator curve (ROC) analysis was performed in order to define the best cut off value.

Results: 75 pts were evaluable. Median age was 67 years (range 42-80); T2a-T2b: 42%;T3a-T3b: 47%; T4a: 11%; G3: 86%. Hydronephrosis was present in 33%. Overall, 56(74.7%) pts achieved a CR and 19 (25.3%) were IR. Bladder was preserved in 53(70.6%).

At a median follow up of 128 months, 28 (37.3%) pts are alive and free of disease (25RC and 3 RI);23 (30.6%) of patients are alive with intact bladder.In the IR group 14 pts(73.7%) relapsed and 10 (52.6%) died for bladder cancer; in the CR group 30 pts(53.5%) relapsed and 21 (37.5%) died for bladder cancer.

Bivariate analysis showed that the achievement of a CR was significantly related tolower T stage (p=0.002), high Ki67 levels (p=0.001), absence of hydronephrosis(p=0.007) and high p53 overespression (p=0.007). However, multivariate analysisshowed that only a low initial T stage (OR=15.9; p=0.009) and an high p53 expression(OR=16.3; p=0.02) maintained an independent role in predicting a complete responseto therapy.

Conclusions: Our results show that high levels of p53 expression is an independentmarker predictive of a complete response to chemoradiotherapy in muscle-infiltratingBC and could help clinicians to better identify responsive pts to whom a bladdersparing approach should be offered.

D16 EARLY EPIRUBICIN-INDUCED MYOCARDIAL DYSFUNCTIONREVEALED BY SERIAL TISSUE DOPPLER ECHOCARDIOGRAPHY(TDI). CORRELATION WITH INFLAMMATORY AND OXIDATIVESTRESS MARKERS

Giovanni Mantovani1, Christian Cadeddu2, Alessandra Piras2, Mariele DessI1,Clelia Madeddu1, Martino Deidda2, Roberto Serpe1, Elena Massa1 and GiuseppeMercuro2

1Department of Medical Oncology and Department of 2Cardiovascular andNeurological Sciences and, University of Cagliari, Italy

A phase II open non randomised trial was carried out in a group of epirubicin-treatedpatients with cancer at different sites with the aim to detect early preclinical changes,predictive of risk of heart failure. All subjects underwent conventionalechocardiography, as well as tissue Doppler imaging (TDI) with Strain (R) and StrainRate (SR), a very accurate technique in detecting minimal changes in the cardiac leftventricular (LV) function. Moreover, echocardiographic changes were compared withthose of a series of biochemical markers of both myocardial damage and inflammation/oxidative stress. Sixteen patients with histologically confirmed tumors at different sites,scheduled to be treated with epirubicin-based chemotherapy were enrolled. Asignificant impairment of the systolic LV function was observed at epirubicin 200 mg/m2; the SR peak decreased significantly in comparison to baseline (1.82±0.57 sec-1 vs1.45±0.44 sec-1), whereas the R remained unchanged. The following significant changesof LV diastolic function occurred, only after the epirubicin dose of 300 mg/m2:a decrease of conventional E/A (1.16±0.31 vs. 0.93±0.24), and a reduction of both Emwave (8.86±1.73 cm/sec vs. 7.51±2.30 cm/sec) and of Em/Am ratio (1.09±0.51 vs.0.83±0.51), measured with TDI technique. No significant changes of LV ejectionfraction were observed. Levels of IL-6, sIL-6R and ROS increased significantly, whilstGPx decreased significantly after epirubicin 200 mg/m2. A significant correlationbetween the reduction of SR peak (DSR) at epirubicin 200 mg/m2 and increase of IL-6/ROS and decrease of GPx was observed. The multiple regression analysis showed thatthe only independent predictive variable of DSR was ROS level. Our data show that: a.subtle cardiac abnormalities may occur at epirubicin doses significantly below thoseknown to be potentially clinically harmful; b. earliest myocardial impairment affects theLV systolic rather than diastolic function. Early contractility impairment was associatedwith high levels of ROS and markers of inflammation. The clinical meaningfulness ofour findings warrants further investigations on a higher number of patients for a longerperiod of follow-up.

D17 OSTEONECROSIS OF THE JAW (ONJ) IN PATIENTS (PTS)TREATED WITH BISPHOSPHONATES (BP): A REGIONALEXPERIENCE

V. Fusco^, A. Vandone, R. Vormola", G. Gorzegno^^, S. Miraglia, L. Ciuffreda,C. Ortega", A. Baraldi*, G. Siffredi^, and O. BertettoSC Oncologia^ & Ematologia*, ASO Alessandria; Oncologia-COES, Torino;IRCC Candiolo"; Oncologia ASO Orbassano^^; Oncologia ASO Novara (onbehalf of ‘‘Rete Oncologica Piemonte-VdA’’)

Since 2003, reports of ONJ in pts treated with BPs, mainly with Pamidronate (P) andZoledronic Acid (Z), are increasing. Our regional oncology network (Rete Oncologicadi Piemonte e Valle d’Aosta), organized a ONJ Study Group, asking for extensivecollaboration of oncologists, haematologists, maxillofacial surgeons,odontostomatologists, to collect cases of ONJ, to enlarge information, and to diffuseguidelines for diagnosis and prevention.Methods: We contacted centres of dental and onco-haematologic care, organizedmeetings and elaborated newsletters.

Results:We collected (on March 2007) 142 cases of ONJ, in patients affected by breastcancer (60), myeloma (45), prostatic cancer (19), other types of cancer (13),osteoporosis or Paget’s disease (5). Pts characteristics: Sex: 53/89 M/F ; median age 71yrs (range 44-84). Full details of BP treatment and dental history have been collected sofar of 103 cases, treated with Z (72), P (27, 19 of which had been ‘‘switched’’ to Z),alendronate/risedronate(4). Characteristics of these cases reflected those described inliterature, in terms of onset findings and dental comorbidities or precipitating events(teeth extraction, etc).

Conclusions: Our 142 cases, observed in a population of 4.3 million, are more thanexpected on the basis of some published estimations of incidence, for example thosebased on data concerning Australia (158 cases in a population of 20.3 million) or evenonly South Australia (25 cases, out of 1.5 million) (Mavrokokki T et al, J. OralMaxillofac. Surg. 2007). Our oncology network recommended: a) screening of all ptsunder treatment with BP; b) careful evaluation of pts candidate to be treated with BP,with pretherapy dental care if necessary; c) prospective evaluation of incidence infuture, avoiding (as possible) surgical dental procedures during BP treatment; d)a case-control study to search possible risk factors of ONJ (treatment- and clinicalhistory-related).

D18 BONE METASTASES FROM PRIMARY CARDIAC SARCOMA

C. Strina1, M Zannoni2, V. Parolin1, R. Sabbioni1, G. L. Cetto1 and S. Zuliani11Department of Clinical and Experimental Medicine, Section of MedicalOncology University of Verona, Italy




ownloaded from


In January 2003, because of the persistence of dyspnea and episodes of lipothymia,a 33-year-old woman underwent cardiac exams and CT, which showed the presence oftwo left endo-atrial masses.

She had surgery to remove the two masses. The histological exam was diagnostic forcardiac leiomyosarcoma.

Eight months later there was a local relapse wich was surgically removed.From October 2003 to May 2004 she had 5 cycles of adjuvant chemotherapy with

Epirubicina and Ifosfamide and adjuvant radiotherapy on the cardiac area.In June 2005, following the appearance of pain in the right hip, she had an X-ray of

this zone, which showed a lytic lesion. This was confirmed by a bone scintigraphy. Shehad also a NMR of pelvis and of right thigh-bone, which showed a solid expansiveformation, situated in the hip-bone and involving the little gluteal and the iliac muscle.Taking into consideration the particularity of the seats of the secondary localization,the patient undergo an abscission biopsy of the right para-iliac neoformation anda biopsy of the diaphysis of the right thigh-bone.

The histology was: metastasis of leiomyosarcoma with morphological characteristicssimilar to the primitive cardiac lesion.

From July to October 2005 she had three cycles of chemotherapy with Ifosfamide incontinuous infusion; interrupted because of the appearance of cardiac toxicity.

Therefore the patient underwent radiotherapy in the seats of the disease. The patientwas followed up at home until March-April 2006, when, due to the appearance ofintense pain in the right leg, she had a bone scintigraphy, which showed lytic area of theleft tibia too. She died five months after due to cardiac progression.

Primary malignant cardiac tumours are extremely rare with an incidence between0.0017% and 0.019% and primary cardiac leiomyosarcomas are rare, account for 8% to9% of all malignant cardiac tumours. Bone metastasis are extremely rare, and this caserepresents only the 4th such case reported of the current literature.

D19 CONCOMITANT CHEMO-RADIOTHERAPY IN NASOPHARYNXUNDIFFERENTIATED CARCINOMA

•R. Grillo, •C. Barone, •F. Gaspari, •E. Larovere, •D. Dongiovanni, M. Rampino,F. Migliaccio, F. Munoz, •L. Buffoni, •N Birocco, •L. Fanchini, U. Ricardi,•L. Ciuffreda, •M. Schena•SC Oncologia Medica-COES- ASO S. Giovanni Battista di Torino, SCDURadioterapia- Universita di Torino- ASO S. Giovanni Battista

Background: Nasopharynx undifferentiated carcinoma is a relatively rare neoplasiaEBV correlated, usually diagnosed as locally advanced disease. Chemoradioterapy isactually considered the standard treatment in this setting. Aim of our study was toevaluate early and late toxicity and outcome among patients treated with standardchemo-radiotherapy between 2000 and 2006 in our institution.

Methods: 23 patients with hystological diagnosis of nasopharynx undifferentiatedcarcinoma have been treated, median age 51 years (range 29-75), 20 males e 3 females,21 patients were PS ECOG 0, 2 patients were PS 2; 3 patients presented IIA stage,1 patient IIB, 16 patients III stage, 2 patients IVA stage and 1 patient IVB stage.Treatment schedule was based on chemotherapy (CT) with cisplatin (DDP) 100mg/mq for three cycles, concomitant to standard radiotherapy (RT) 70,20 Gy,followed by two cycles of consolidation CT with Cisplatin 100 mg/mq + 5fluorouracile1000 mg/m2/die for five days in continuous infusion.

Results: 21 patients (91%) obtained a complete response (CR) to therapy, while twopatient obtained only a partial response (PR). Three patients presented loco-regionalprogression of disease after CR, have been treated with salvage CT regimen and arestill alive. After a median follow up of 4 months (range 50-3) median overall survivaland progression free survival have not been reached yet. During the treatment weobserved toxicity of 3-4 grade. In 6 cases (26%) this toxicity required hospitaladmission with an average length of 15 days.Artificial nutritive support wasnecessary with SNG or PEG in 6 patients (26%).Prevalent late toxicity were G1-G2xerostomia (80%) and ototoxicity (21%).

Conclusion: Concomitant chemo-radiotherapy in nasopharynx carcinoma is activebut characterized by high acute toxicity during treatment and an optimal supportivecare is necessary in order to complete the therapeutic program. Late toxicity appearsmodest but a QoL study is needed.

D20 FEASIBILITY AND LOW TOXICITIES OF RADIATIONRETREATMENTS WITH HELICAL TOMOTHERAPY

F. Alongi1, N. Di Muzio1, M. Caimi1, G. Berardi1, D. Aldrighetti4, M. Pasetti1,C. Landoni2, F. Fazio1,2,3

1Department of Radiation Oncology Scientific, Institute San Raffaele, Milano;2Department of Nuclear Medicine, Scientific Institute San Raffaele, Milano;3IBFM-CNR-University of Milano-Bicocca, Milano, Italy; 4Department of MedicalOncology, Scientific Institute San Raffaele, Milano

Purpose: It is difficult to successfully deliver a second course of radiation therapy forpatients with overlapping treatment volumes. The aim of this study is the evaluation ofHelical Tomotherapy for retreatment of cancer recurrences in various anatomical sites.

Methods and Matherials : From January 2005 to March 2007 20 patients underwentradiation retreatment. The sites of second irradiation were: 10/20 metastatic lymphnode, 2/20 bone metastasis; 3/20 lung cancer recurrence, 2/20 head and neck

recurrences 2/20 are breast recurrence 1/20 primitive cancers. In 11/20 cases the targetvolumes were totally included in previously irradiated volume but in 9/20 theoverlapping treated volume was only partially. For every patient a full dose wasdelivered taking into account the disease to be treated. Every patient had a treatmentplanning including PET/TC. The expansion of Planning Target were driven by: thebiology of the disease to be treated, the dose distribution on organs at risk (OAR), thetotal dose received by the OAR and the interval time from previous irradiation.

Results: The acute toxicity of the entire group of patients was as follows : G0 in 9/20patients, G1 ( cutaneous or mucosal ) in 8/20, 3 G2, 0 G3. 11/20 patients are incomplete response, 7/20 presented partial response, and 2/20 are in progression witha median follow up of 14 months (range 4-26 months). The response evaluation wascarried out with PET/TC at 1-3-6-9-12 months after radiation retreatment.

Conclusions: In our preliminary experience radiation retreatment performed withimage guided helical Tomotherapy is a safe and effective treatment modality in selectedcases of recurring cancer disease. Treatment planning based on PET/CT is useful todefine the real extension of the disease in order to decrease the irradiation of the OAR.However further investigation is warranted to consolidate these results and to extendthese indications to other clinical situations.

D21 ELECTROCHEMOTHERAPY (ECT) FOR THE TREATMENT OFSUPERFICIAL TUMOR LOCALIZATIONS

Guida M*, Porcelli G, Monticelli G*,Montemurro S, Colucci G**Department of Medical Oncology; Department of Surgery Istituto Tumori‘‘Giovanni Paolo II’’, Bari, Italy

Introduction: ECT is an effective local treatment for palliation on inoperablesuperficial neoplastic localizations which combines delivery of chemotherapeutic drug(either systemic or local) and electric pulses that permeabilize the cell membrane ina transient and reversible manner, allowing low-permeant anticancer drugs(Bleomicin, Cis-platin), to enter the cell, thus magnifying their cytotoxicity. Recently, ithas been developed a new device (Clinoporetor, IGEA S.r.l.) able to supply electricpulses with appropriate and standardized parameters regarding amplitude, duration,number, repetition, frequency and shape. Clinoporetor has permitted to translate basicresearch into a routinely treatment modality for the treatment of superficial lesionsfrom any type of tumour inducing a very high percentage of responses. Treatment ismostly used in local anaesthesia and showed a safe and well tolerated profile alsopermitting organ and function sparing.

Methods and results: We are carrying out a trial with the Cliniporator devise in ptswith superficial localizations from different tumors. Until now, 5 female pts weretreated: 2 in transit melanoma metastases of the inferior limbs; 1 high grade lymphomawith two cutaneous localizations on the right leg; 2 breast cancer (1 pt with a largepolypoid ulcerated lesion relapsed on the pectoral pre-irradiated area; 1 pt withmultiple cutaneous/subcutaneous nodules with an haemorrhagic and ulceratedcomponent. The treatment was performed on an out-patient basis. Local anaesthesiaand intravenous infusion of Bleomycin (15 mg/m2) were used in all patient; electricpulses were than applied to the tumor areas by needle electrodes in a time window ofabout 20 minutes. Totally, we treated 80 lesions. Starting from the second/third weekfrom treatment, all pts showed a regression of almost all treated lesions with a slow,progressive necrotic evolution. One melanoma pt requested a second applicationbecause of the appearing of new in transit lesions.

Conclusions:Our preliminary data confirm that ECT is a promising and safe treatmentfor superficial lesions from different malignancies.

D22 AUTOLOGOUSSTEM CELL TRANSPLANTATION INHEMATOLOGIC MALIGNANCIES AND SOLID TUMOURS: OUREXPERIENCE

Annalisa Luraschi, Paola Buscaglia, Paola fedeli, sergio Montanara, Elvira Uccelliand sergio CozziRegione Piemonte ASL14VCO Oncology Unit Verbania

Myeloablative therapy with HSCT is an accepted treatment modality in lympho-haemopoietic malignancies and solid tumours. We describe our experience of 45HSCT performed: 20 patients affected by Myeloma (10 double transplants) medianage 64 years(range 52-75); 10 by NHL, median age 49.4 (36-71); and 4 by metastaticbreast cancer, median age 48.5 years (37-61).

Mobilisation of HSC was achieved by myelosuppressive chemotherapy and myeloidgrowth factor: CTX or D-CEP for Myeloma, DHAP or HDAC +/- Rituximab inNHL and FEC 100 or CTX in breast cancer.

CD34 harvests were satisfying: 9.8 x 106 CD34/kg (range 3-18) for myelomapatients, 19.4 (10.2-41) for NHL and 9.27 (7.8- 10) for metastatic breast cancer.

Before autologous HSCT standard conditioning regiments were given: Melphalanin Myeloma, BEAM (8 patients) or Melphalan (2 patients) in NHL, Melphalan +Mitoxantrone or Etoposide + Carboplatin in Breast cancer.

In all patients the aplastic phase was fast: neutrophil recovery >500/ul was 5.3days (range 1-9), platelets recovery >20000/ul was 1.5 days ( 0-5). Transfusionsupport: red cell transfusions 1.8 (range 0-7), platelets transfusion 1.5 (0-4).




Dow

nloaded from


During neutropenic phase, autologous HSCT patients were hospitalised in singleroom with air and water quality control trough filtration. During neutropenic phasepatients were treated prophylactically with ciprofloxacin and itraconazole.

Treatment related mortality (TRM) is 0%. Infective complications were: 1 HZVinfection, 1 HBV infection, 1 Aspergillus sinusitis and 2 CMV reactivations treated withpre-emptive therapy.

In the Myeloma group 11 patients are still alive: 1 in CR (58 months after HSCT), 11in PR and 1 in RD; 9 patients died for relapsed and progressive disease (15-88 monthsfrom HSCT).

In the Lymphoma group 8 patients are alive: 7 in CR and 1 in RD (75 months fromtransplant); 2 died: 1 in RD 32 months from HSCT and the second for PD after 2months.

All patients affected by metastatic breast cancer died (4-18 months from HSCT), allin RD.

D23 SAFETY OF LONG-TERM (> 2 YEARS) ZOLEDRONIC ACID (ZA)TREATMENT FOR BONE METASTASES (BM)

Guido Vietti Ramus, Alfredo Addeo, Marianna Paola Sirgiovanni, Laura TondaOncologia Medica, Ospedale San Giovanni Bosco, Torino

Zoledronic acid (ZA) is approved for bone metastases (BM). Clinical guidelinessuggest to continue ZA until adverse events or tumor progression. Major adverseevents (MAE) are renal failure (RF), osteonecrosis of the jaw (OJ) and symptomatichypocalcemia (SH). There are conflicting results and no evidence-based consensusabout risk factors favoring MAE, mostly about the impact of long-term ZA treatment(usually considered > 2 yrs). We compared MAE frequence in the whole group of ptstreated with ZA after 2001 with the subgroup of long-term treated (LTT) pts (> 2 yrs ofZA exposure). ZA was administered 4 mg every 4 weeks. All pts received also:immediately after ZA 4 g calcium gluconate iv in 2 hours; daily os calcium carbonate(1 g) and vitaminD3 (880 U). We treated 129 pz (59 women, 70 men). Median age was74 yrs (33 to 88). Primary tumors were: 14 myeloma (M), 41 breast (B), 32 prostate (P),7 renal (R), 19 NSCLC, 6 SCLC, 3 gastric, 3 bladder, 1 neck, 1 colon, 1 liver, 1 cervical.

ZA infusions were 1888 (15 +/- 13 /pt, with median 10/pt, range 2 to 59). Timeof exposure to ZA was less than 2 yrs for 102 pts, more than 2 yrs for 27 pts (5 M, 17 B, 3P, 2 R).The ZA infusions in pts LTT were 36 +/- 11 cycles/pt. 99 pts died. After thediagnosis of BM the median survival was 12 months: M 24, B 24, P 18, R 11, NSCLC 7,SCLC 9 months. 13 pts (10%) had pathological fractures during ZA treatment: 3 M, 5B, 3 P, 1 NSCLC, 1 R. RF was observed in 11 pts (8.5%), of these pts 5 were LTT(18.5%) (p < 0.05); OJ in 2 pts (1.6%), 1 LTT (3.7%) (1 pt received 13 and 1 pt 25 ZAinfusions) (p NS); SH in 4 pts (3.1%), 2 LTT (7.4%) (p NS). The MAE increasedwith ZA infusions number: 8% from 1 to 12 (6/78 pts), 12% from 13 to 24 (3/24 pts),21% from 25 to 36 (4/19 pts), 33% from 37 to 48 (1/3 pts), 40% from 49 to 60 (2/5 pts). The MAE was RF: it developed after an average of 22 months of ZA use (range 3to 50). It developed in 21% of M (3/14 pts), in 10% of B (4/41 pts) and in 12% of P(4/32 pts). Pts with RF received 22 +/- 15 ZA infusions, whereas pts with no RF 14 +/-13 (p < 0.1). Our retrospective analysis shows that long lasting ZA exposure isassociated with MAE incidence. The most frequent MAE event is RF, especially in LTTand in M. In cancer pts creatinine increase is often multifactorial, but acute tubularnecrosis associated ZA use may play an important role. The onset of RF and the partialrecovery of serum creatinine after ZA discontinuation suggest a cumulative doseeffect and a temporal exposure relation to ZA. It is necessary monitor renal function,mainly in LTT and in M, and discontinue ZA if it worsens. Caution is required for ZAuse beyond 2 yrs in these tumors. Further studies are required to investigate if lessfrequent ZA dose reduce major toxicities with same benefit.

D24 ANTITHROMBOTIC PROPHYLAXIS (ATP) IN CANCERPATIENTS WITH CENTRAL VENOUS CATHETER (CVC).META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS (RCT)

Tassinari D1,2, Scarpi E3, Tamburini E2, Rupoli S4, Leoni P4

1Supportive and Palliative Care Unit; 2Department of Oncology, City Hospital,Rimini; 3Department of Oncology, City Hospital, ForlI; 4Department ofHaematology, University of Ancona

Background: To assess the role of ATP in cancer patients with CVC.

Methods: A systematic review of literature from 1966 to 2006, using ‘‘anticoagulants/*administration & dosage’’[MeSH term], ‘‘cancer patient’’ [MeSH term],‘‘catheterization, central venous/*adverse effect’’ [MeSH term], ‘‘catheters, indwelling/adverse effects’’ ‘‘central venous catheter’’ [MeSH term], ‘‘neoplasm/drug therapy’’[MeSH term], ‘‘venous thrombosis/*etiology/*prevention & control/radiography’’[MeSH term],as search terms was performed independently by two authors (DT andES). All the RCT comparing ATP [Low Molecular Weight Heparin (LMWE) orWarfarin (W)] and placebo were considered eligible and included into the analysis. Therisk reduction (RR) of upper limb venous thrombosis (ULVT) was the primaryoutcome of the analysis. The quality of reported data was assessed using the Nicolucciand Jadad scores. Heterogeneity between the trials was assessed using the Mantel-Haenszel test, and the outcome analysis was performed using a random effects modeland an alpha error<5%. Cumulative (LMWE+W) and distinctive (LMWE and W)analysis were performed, and the RR was assessed in all the 3 different conditions(LMWE, W and LMWE+W).

Results: 8 trials met the selection criteria and were included into the analysis. 5 trialscompared LMWH and placebo, and 3 W and placebo. The outcome of 1846 patients(814 treated with LMWE, 217 with W and 815 with placebo) was compared in thepooled analysis. A significant heterogeneity was documented between the trials(p=0.026), but it was excluded when trials with a low quality score (2 ones) were notincluded into the analysis (p=0.89). No significant differences in RR were observedboth when all the trials were included into the analysis (RR=2.8%, p=0.34) or when weexcluded the low-quality ones (RR=0.3%, p=0.81). Likewise, no significant RR wasobserved when LMWE or W were considered separately (RR=2.4%, p=0.45 andRR=5.7%, p=0.48, respectively).

Conclusion: ATP with LMWH or W does not reduce the risk of ULVT in oncologicpatients withCVC, and its routine use seems to be not-recommended in clinical practice.

D25 EPOETINS AMELIORATE ANEMIA WHEN ADMINISTERED TOPATIENTS WITH B-THALASSEMIA MINOR WITH SOLID TUMORSUNDERGOING CHEMOTHERAPY

Fiorenza Latteri, Hector Soto Parra, Roberto Bordonaro, Stefano Cordio,Giuseppe Lavenia, Emilia Medulla, Carmelo MagnanoOperative Unit of Medical Oncology, Ospedale Garibaldi Nesima, Catania, Sicily,Italy and Thalassemia Unit, Ospedale San Luigi, Catania, Sicily, Italy

Background: B-Thalassemia minor (B-Tm) is the most common hereditary disorder inthe Mediterranean region with a prevalence of 6% in Sicily. B-Tm is characterised bymild anemia (A). Therefore, we performed a retrospective analysis to evaluate thecourse of A in B-Tm pts with solid tumors (ST) undergoing chemotherapy (CT).

Methods: B-Tm pts with ST were identified from our clinical record database [historyand/or hemoglobin (Hb) A2 level > 3.3%]. Inclusion criteria were first-line or second-line CT after a CT-free interval of 6 mos and complete blood count evaluations everycycle. Exclusion criteria:concomitant radiotherapy (RT), or previous RT to the pelvicregion, or active bleeding.

Results: From July 2004 until the present day, 30 B-Tm pts with ST have beenobserved, and 23 fulfil the criteria of this analysis. The pt demography was as follows:median age, 56 years (range, 38–76 years); Males: 9 pts; PS 0/1: 19/4; stage IV: 10; typesof cancers: breast, 7, gastrointestinal, 7, lung, 4, others, 5; previous surgery within 2 mosbefore CT: 12; platinum containing regimen: 7. A was evaluated during the first andsecond-line treatments in 19 and 4 pts, respectively. The mean values of Hb (gr/dl +/–SD) at baseline and at lowes value during CT were respectively 11.06 +/-1.47 and 9.1 +/-1. The incidence of pts with mild (from >10 and <12 gr/dl) or moderate (<10 gr/dl) Aduring CT, were as follows: baseline 40% and 30%; during CT 35 % and 55%respectively. No paradoxical effect of CT on the Hb level was observed. One pt receivedtransfusions (Hb level, 7.8 gr/dl). Nine pts were treated with epoetin (darbepoetin alfa,7 pts and epoetin beta, 2 pts) and iron supplements due to worsening A (mean Hbvalue = 9 gr/dl +/– 0.6). Five pts experienced a >2 gr/dl increase in the Hb level at 8weeks, one experienced a >1 gr/dl increase, one had stable values = 9 gr/dl, and two ptshad decreased values, i.e., 7.3 gr/dl and 6.9 gr/dl, and required transfusions.

Conclusion: This analysis demonstrates that 70% of B-Tm pts with ST have mild ormoderate A prior to CT. The A of B-Tm patients is worsened by CT and results inmoderate A in 55% of the pts. Epoetins, particularly darbepoetin alfa, effectivelyameliorate A when administered to pts with Hb levels of <10 gr/dl. This data suggeststhat epoetin treatment during CT may benefit B-Tm pts. Prospective trial is required.

D26 PROTECTIVE EFFECT OF ACETYL-L-CARNITINE (ALC) ANDPYRIDOXINE CHLORHYDRATE (PC) IN NEUROTOXICITY INDUCEDBY PACLITAXEL CHEMOTHERAPY IN OVARIAN CANCER : A SINGLEINSTITUTION STUDY

A. M. L. Capobianco, A. Tartarone, A. M. Bochicchio, M. Coccaro, P. Di Leo,C. Romano and R. ArditoOperative Unit of Oncology- CROB -Rionero in Vulture-( PZ)- Italy

Background: Cumulative Peripheral Neuropathy (CPN) is one of the most frequentside effects of taxanes -chemotherapy, it is a limitation to optimal treatment and worsesQuality of Life of the patients.

The aim of this study is to determine if ACETYL-L-CARNITINE and PYRIDOXINECHLORHYDRATE are effective drugs in improving pain and symptoms due to CPNPaclitaxel-induced. Many studies showed that treatment with ACL, lowing thenociceptive threshold and with PC, a coenzyme of the proteic and lipidic metabolism,is able to reduce the CPN Paclitaxel-induced.

Methods and Results: From July 2006 to February 2007, 15 patients with ovariancancer (adjuvant or advanced disease), mean age 56 years (range 40-75), PS ECOG 0-1,were assigned to receive Carboplatin (AUC 5) and Paclitaxel (175 mgr/m2 ) q21 for sixcycles. All patients at the start of chemotherapy received supplementation with ALC300 mgr twice a day and PC 300 mgr /day for fourteen days after each cycle ofchemotherapy, these patients were considered group A. Toxicity and compliance werecompared to those of 15 patients, served as controls and considered group B, treatedpreviously in our institution with only Carboplatin and Paclitaxel without protectivedrugs. Toxicity was coded by NCI-CTC with a complete neurological examination:distal paresthesia and dysesthesia, muscle weakness, sensory-motor symptoms,tinnitus.




ownloaded from


Grade 3-4 neurotoxicity was observed in 0/15 patients of group A vs 3/15 (20%)patients of group B.

Grade 1-2 neurotoxicity was observed in 3 /15 (20%) patients of group A and 13/15(86%) patients of the group B. Treatment compliance, related only to CPN Paclitaxel-induced, in group A compared to group B was respectively: 100% vs 93% for theadministered cycles and 6.6% vs 22% for dose reduction.

Conclusions: Considering the absence of any satisfactory treatment currently availablefor CPN, these results suggest that ALC and PC, drugs with an excellent safety profile,can prevent or reduce CPN Paclitaxel -induced and improve the QofL; these resultsneed further investigation.

D27 PRIMARY GASTRIC NON HODGKIN’S LYMPHOMA (PGNHL):A MONOISTITUTIONAL EXPERIENCE

B. Soini, A. Ferro, O. Caffo, V. Murgia, F. Valduga, G. Ambrosini, M. Frisinghelli,S. Brugnara, A. Caldara, *A. Bolner, **D. Aldovini, E. GalligioniUnits of Medical Oncology, * Radiotherapy and ** Pathology St Chiara Hospital,Trento, Italy

Introduction: Primary gastric lymphomas are the most common extranodal non-Hodgkin’s lymphomas (NHL). Conservative treatment with anthracycline-containingchemotherapy, followed or not by involved field radiotherapy has replaced gastrectomyas standard approach against this malignancy, but several questions on the besttreatment remain unanswered.

The aim of this retrospective study was to evaluate the clinico-pathologicalpresentation and the treatment results, in patients with PGNHL treated at ourinstitution.

Methods: Among 124 patients with NHL followed from 2001 to 2006 at ourinstitution, 15 PGNHL (12 %) were diagnosed. There were 7 males and 8 females withmedian age of 72 years (range 49 – 83). Sixty seven percent of the patients (10/15) werein stages I - II, and 33 % (5/15) in stages III – IV. The predominant istological type wasdiffuse large B-cell lymphoma (DLBCL) (14/15) and Burkitt’s like Lymphoma (1/15).Simultaneous involvement of the stomach and other extranodal sites was observed in 4pts (26 %). Sixty seven percent of patients (10/15) received frontline chemotherapy(CHOP, R-CHOP or CHOP like regimens) and 33 % (5/15) underwent primarysurgery, followed chemotherapy in 2 cases.

Results: Among the 10 patients receiving frontline chemotherapy (+/- Rituximab), 7CRs, 1 PR, 1 PDs were observed, while 1 pt is not evaluable. Except for this patient, diedfor infection during G4 neutropenia, the treatment was well tolerated. All patientsreceiving primary surgery +/- chemotherapy were NED after treatment. Progressionfree survival (PFS) in patients treated with chemotherapy was 27 months (range 4 - 78)and overall survival (OS) was 33 months (range 9 - 84). In patients treated with surgeryPFS was 43 months (range 7-71) and OS was 43 months (range 3-71). Global PFS was29 months (range 4 - 78 months) and global OS was 34 months (range 9 - 84) in allpatient population.

Conclusion: It appears from our experience that for patients non suitable for orrefusing chemotherapy, gastrectomy can be considered, mainly for elderly patients orthose with massive bleeding or perforation at presentation.

D28 EARLY DIAGNOSIS OF SKIN CANCER : UTILITY OF APREVENTION PROGRAM IN AN INDUSTRIALIZED AREA

1S. Chiado Cutin, 2L. Santoro, 1A. Boglione, 1P. Bergnolo, 1C. Oliva, 1O. DalCanton, 2A. Farnetti, 2R. Mattio, 1P. Pochettino, 1M. InguI, 1F. Garetto,1A. Comandone1Unita Operativa Oncologia Ospedale Gradenigo, Torino 2Servizio diDermochirurgia Oncologica Ospedale Gradenigo, Torino

Malignant Melanoma (MM) represents about the 5% of malignant tumours in Europeand US. In Italy the incidence is 8-10/100.000 cases, with a peak between 35-50 years.

Non-melanoma skin cancers (75% basal and 15-20% squamous carcinoma) representthe most frequent tumours among males (15,2% of all cancers) and the second (14,8%)among females. In Italy the incidence is increasing with 2-3%/year-rate.

Early MM is usually visible and detection of thin lesions is associated with a bettersurvival: the 10 years overall survival after resection of tumours < 1.00 mm is about 90%.

Epithelial skin cancers rarely result in death, they are common and can recur andmetastasize.

Skin cancer diagnosis is often occasional or subsequent to evidence of clinical signs.Italian Cancer Registry shows that incidence rates x 100,000 by Breslow thickess is:

37.7% <1mm, 18% 1-1,99 mm, 26,3% 2- 3.99 mm, 18% £ 4 mm.Since 2005 we started a screening program with the Dermosurgical Unit, on the

behalf of the ‘‘Associazione per la Prevenzione e Cura dei Tumori in Piemonte’’.The program includes free skin examination addressed to the population of Torino

and Piedmont informed by newspapers, TV, internet.Data were obtained on a total of 4620 visits.Mean age was 44,6 years (13-89), female (59%), skin phototype II-III in 69%,

childhood sunburn in 47% of cases.15 out of the 204 suspicious melanocitic lesions were histologically proven to

be MM, 8 of which (53,3%) were ‘thin’ melanomas (Breslow ‡ 1 mm), 26, 7%1-1,99 mm, 13.4% 2-3,99 mm, 6,6% > 4 mm. 112 dysplastic nevi have beenremoved.

About non-melanocitic lesions 278 basal and 25 squamous cell carcinomas havebeen found.

Our study confirms that a skin cancer prevention program in a industrialised zonecan increase the early detection of pathological lesions and improve the out-come ofdisease. It better clarifies epidemiology of these tumours in a geographic area. Ascreening program could be planning in general population.

D29 SAFETY PROFILE OF TEMOZOLOMIDE CONCOMITANT TORADIOTHERAPY (RT) FOLLOWED BY PROLONGED MAINTENANCECHEMOTHERAPY IN NEWLY DIAGNOSED GBM

Tosoni Alicia1, Franceschi Enrico1, Bartolini Stefania1, Blatt Valeria2, CompostellaAlessia2, Degli Esposti Roberta1, Andreoli Alvaro3, Paioli Anna1, Ermani Mario4,Brandes Alba A1

Oncology Department1 and Neurosurgery Department 3 of Bellaria-MaggioreHospital, Azienda –USL di Bologna; Oncology Department, Istituto OncologicoVeneto-IRCCS Padova2; Statistic and Informatic Unit, NeurosciencesDepartment4, Padova University, Italy

Background: TMZ concomitant to RT followed by 6 cycles of adjuvant TMZ hasbecome standard of care in the treatment of newly diagnosed GBM, obtaininga statistical significant survival benefit over radiotherapy alone. In this studyconcomitant and adjuvant part, demonstrated grade 3-4 hematological toxicity in 7%and 14% of patients respectively.

Methods: Adult GBM patients were treated with TMZ (75 mg/m2/day) concomitant toRT (60 Gy/30F) followed by adjuvant TMZ (150-200 mg/m2 days 1-5, q28). AdjuvantTMZ was continued for a maximum of 12 cycles in patients with no evidence of diseaseand until progression in patients with evidence of disease. Prophylactic trimetoprim-sulphamethoxazole 3 times weekly was administered.

Results: 104 patients (67 males), median age 53 (range 20-73), median KPS 90 wereenrolled. A median of 6 cycles of adjuvant TMZ were delivered (range 0-30). Duringthe concomitant phase, grade 4 neutropenia occurred in 1 patient (0.9%), and grade3-4 thrombocytopenia in 4 patients (3.8%). Grade 1 to 2 lymphocytopenia occurred in10 patients (9.6%). One patient reported pneumonia with normal white blood cells.Five patients (4.8%) discontinued treatment in the concomitant part: 2 for grade3 dermatological rash, 2 for haematological toxicity (one for prolonged grade 4thrombocytopenia resolved in 6 weeks, and 1 patient for grade 4 neutropenia andthrombocytopenia, still unresolved after more than 15 months). One patient died afterconcomitant treatment for pulmonary embolism. During the adjuvant phase, grade3 to 4 neutropenia and thrombocytopenia occurred in 2% and 5% of patients,respectively. Two patients discontinued treatment in the adjuvant part, one at thirdcycle for prolonged grade 4 thrombocytopenia, and one after fifth cycle for prolongedgrade 2 thrombocytopenia.

Conclusions: A prolonged maintenance TMZ chemotherapy doesn’t impact negativelyon toxicity profile.

D30 OSTEONECROSIS OF THE JAW (ONJ) PREVENTION WITHPIEZOSURGERY FOR TEETH EXTRACTIONS DURING ZOLEDRONICACID USE: A PRELIMINARY EXPERIENCE

F. Goia^, C. Ortega*, F. Montemurro*, P. Appendino^, R. Vormola*, L. Basano^,A. Chiarelli^, M. Aglietta*^Department of Oral Pathology, Mauriziano Umberto I Hospital, Turin,Italy.*University Division of Medical Oncology and Haematology Institute forCancer Research and Treatment (IRCC), Candiolo, Italy

Introduction: Osteonecrosis of the jaw (ONJ) is an oral complication in patients withcancer receiving bisphosphonates (BF). Recent dental extraction and any oral surgicalprocedure are considered local precipitating factors for ONJ. Initiation ofbisphosphonates therapy should be delayed, if possible, until the dental health isoptimised and while on treatment, these patients should avoid invasive dentalprocedures if possible. However, during BF therapy, these procedures cannot be alwaysdelayed. Piezosurgery is a new surgical technique that, using a modulated ultrasonicfrequency, permits highly precise and safe cutting of hard tissue.

Methods: Using the Mectron Piezosurgery� Device for alveolar post-extraction carefollowed by a wound closure with mucous flap, we performed 16 extractions in 8patients who underwent unavoidable surgical procedure during zoledronic acidtreatment for bone metastases from different cancers (breast: 5; multiple myeloma: 3).

Results: Median age was 55 yrs (range 45-75) and median time of zoledronic acidexposure was 16 months (range 5-40). At the present all patients show a completehealing of the oral bone and mucosa and at a median follow-up of 5.5 months no ONJwere registered. All patients restarted zoledronic acid administration after at least twomonths from surgical procedure.

Conclusion: Using Piezosurgery to perform extractions during bisphosphonatestreatment, our patients received surgical treatment with good results. Even if medianfollow-up is short and further data are needed our preliminary experience suggests thatPiezosurgery for unavoidable extractions during BF treatment could be a good optionto control ONJ onset.




Dow

nloaded from


D31 COMPARISON BETWEEN SHORT AND LONG SURVIVORSCONSECUTIVELY DIAGNOSED IN A LARGE HOSPITAL ANDINCLUDED IN THE REGIONAL POPULATION-BASEDMESOTHELIOMA REGISTRY

*Mencoboni M, Montanaro F, Bianchelli M, *Bergaglio M, *Galbusera V, *Racchi O,*Faravelli B,*Tata F, *Faravelli B, *Pastorino G, Lazzarotto A, Gennaro V*Ospedale Villa Scassi Genova-UUOO Oncologia, Pneumologia, ChirurgiaToracica; Registro Mesoteliomi della Liguria-Epidemiologia Descrittiva-IST-Genova

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumour;occupational exposure to asbestos is the most common cause of this cancer in about5% of exposed workers. Prognosis is severe in few months; however, sometimes it ispossible to observe long-term survivors. We do not know exactly if some variables asgender, age at diagnosis, cigarette smoking, histology and occupational exposure couldcorrelate to prognosis.

Methods: We retrospectively studied a consecutive series of 281 patients affected bymalignant pleural mesothelioma (MPM) diagnosed consecutively in ‘‘Villa Scassi’’Hospital from 1994 to 2006. 236 were male; 47 were female. Mean age at diagnosis was68,6 for male, 70,6 for female. As to histology, it was epitheliod in 74% patients,sarcomatoid in 10% patients, biphasic in 8% patients, unspecified in 8% patients.Mean survival was 18 months for male, 19,5 months for female. We divided patientinto short survivors (< 12 months), mean survivors (between 12 and 24 months), longsurvivors (> 24 months). We recorded 142 short survivors (50%), 93 mean survivors(33%), 48 long survivors (17%).

We studied if gender, age at diagnosis, cigarette smoking, histology andoccupational exposure could have relation with survival. We studied male and femaleseparately.

Anova and Chi square tests were adopted to study this population.

Results: As to survival, no statistically difference were recorded between male andfemale patients. In female patients age at diagnosis, cigarette smoking, histology anddefinite occupational exposure had no correlation to survival. In male patients,younger age at diagnosis partially correlate with better survival (mean age in shortsurvivors = 70, mean age in long survivors = 66; P = 0,03). Cigarette smoking had nocorrelation with survival. Epitheloid histology versus other histologies correlate withbetter survival (P >0,01). Definite occupational exposure (versus probable or nonoccupational) correlate partially with better survival.

Conclusions: From this large series of MPM patients we identified a sub-group oflong survivors; epitheloid hystology, younger age at diagnosis and definiteoccupational asbestos exposure in male patients correlate with this better prognosissubgroup.

D32 PRELIMINARY RESULTS OF A PILOT TRIAL ON THE ACTIVITYAND SAFETY OF ADJUVANT THERAPY WITH FOTEMUSTINE ANDCONCOMITANT RADIOTHERAPY IN PATIENTS WITH NEWLYDIAGNOSED ANAPLASTIC ASTROCYTOMA (AA)

Elena Mazza, Micaela Motta, Stefano Cereda, Andrea Falini, Mariarosa Terreni,Alberto Franzin, Piero Picozzi, Stefania Acerno, Paolo Vezzulli, Michele ReniSan Raffaele Hospital Scientific Institute, Milan

Background: Despite intensive treatment, prognosis of patients with AA remainspoor with a median survival time after surgery and radiotherapy of about 36 months.Only few drugs have showed activity in AA. Nitrosoureas are among the most activeagents. The aim of this study is to explore the safety and activity of the newgeneration nitrosourea, fotemustine, concomitant and sequential to radiotherapy inthe treatment of AA.

Methods: Patients with histologically-proven AA (either by biopsy or surgery) atdiagnosis, age > 18 and < 70 years, Karnofsky PS > 60, not previously treated withchemo-radiotherapy, received during radiotherapy (60 Gy in 30 daily fractions)3 weekly infusions of fotemustine (70 mg/m2 ) starting 1 week after the start ofradiotherapy (day 8, 15, 22), followed by ‘‘maintenance’’ therapy with fotemustine at100 mg/m2 every 3 weeks for 5 cycles, starting within 4 weeks after the end ofradiotherapy. Tumor was assessed by MRI scan every 6 -8 weeks.

Results: Between June 2004 and July 2006, 9 patients (median age 45; median KPS 90)were enrolled. Surgery was subtotal resection in 4 cases and biopsy in 5. Fotemustinewas administered for all 6 cycles in 7 patients, while 2 patients received onlyconcomitant fotemustine because of infective complications after G3 or 4 neutropeniarespectively. Grade > 2 haematological toxicity was observed in 4 patients. Partialresponse was obtained in 2 patients. and stable disease in 7 patients. Six patientshad PD.

Median PFS was 14 months (range 5-35 months). Six of 9 patients were free of PD at12 months. Two patients died due to progressive disease and infective complicationsrelated to II line chemotherapy toxicity. Seven patients were alive at 10-36 months(median 19) from surgery. Median OS was 19+ months (range 9-36+).Conclusions: Fotemustine may be administered safely during and after radiotherapy inthe adjuvant management of patients with AA. Preliminary data of activity seem to beencouraging.

D33 POST TRANSPLANTATION LYMPHOPROLIFERATIVEDISORDERS IN HEART AND KIDNEY/PANCREAS TRANSPLANTPATIENTS: A SINGLE-CENTER EXPERIENCE

Silvia Stragliotto, Dario Marino, Micaela Stefani, Gino Crivellari and Savina Aversaoncologia medica 2, Istituto Oncologico Veneto, I.R.C.C.S, Padova, Italy

Background: Post-transplant lymphoproliferative disorders (PTLD) are a fatalcomplication after solid organ transplantation (SOT). Aim of this study, conductedin a single Italian center, was to describe the clinical presentation and outcome of PTLDcomplicating heart or kidney/pancreas transplantation.

Patients and methods: The study involved 30 PTLD (24 males, 6 females) among 1240adult patients underwent organ transplantation between November 1985 to December2006 at University Hospital of Padua. 20 PTLD were diagnosed among 620 hearttransplanted (prevalence 3,2%) and 10 among 920 kidney/pancreas transplanted(prevalence 1%).

Results: At diagnosis of PTLD the median age of patients was 46 years (range 13-71).The median time from transplantation to onset PTLD was 6,5 years (range <1-16 years)with 4 early PTLD (<1 year). 12 patients were at I stage, 4 at II, 4 at III and 10 at IV.13/30 patients had B symptoms and 6/30 bulky disease. 16/30 had an extra nodalpresentation. Among the 30 patients with PTLD 1 refused any treatment and diedwithin few days, 5 have been treated with reduction/withdrawal of immunosuppressiondrug, 20 with weekly chemotherapy and the other 4 with a combination of surgery +/-radiotherapy. No patient develops allograft rejection and no severe adverse events wereobserved in chemotherapy group. At the moment 19/30 patients are alive with anmedian follow up of 36 months. The estimated overall survival at 5 years of all patientsis 63,3% with a median survival of 82 month.

Conclusion: This prospective study of 30 cases of PTLD differs from prior studiesbecause the population is rather homogeneous and the patients were treated ina relatively uniform fashion by reduction/withdrawal of immunosuppression +/-chemotherapy. The novel anti-CD20 monoclonal antibody will have to be consideredin the next treatment of this patients.

More data about histology, EBV role and treatment schedule will be presented at theconference.

D34 LOCAL CONTROL IN NON-METASTATIC EWING’S SARCOMA

Stefano Ferrari, Enza Barbieri, Emanuela Palmerini, Lorenza Gandola, RobertoLuksch, Sergio Mappelli, Amelia Tienghi, Gabriella Bernini, Adalberto Brach delPrever, Piero Picci, Mario MercuriIstituto Ortopedico Rizzoli

Background: Local recurrence negatively affects prognosis in Ewing’s sarcoma (ES).An analysis of factors influencing local control in nonmetastatic ES was performed.

Methods: Patients enrolled in ISG/SSG-3 protocol from 1999 to 2006 and who receiveddefinitive local treatment were included. Induction chemotherapy with vincristin,doxorubicin, cyclophosphamide, ifosfamide, actinomycin, etoposide was followed byhigh dose busulfan and melphalan and stem cell support in patients with poor response(PR). Patients with good response (GR) to induction treatment received the samedrugs in the maintenance phase. Whenever possible surgery (S) was recommended. Incase of inadequate surgical margins radiotherapy (RT) (42-54 Gy) was mandatory.Postoperative RT was allowed on a clinical basis decision. RT (54 Gy) only wasemployed when surgery was not feasible.

Results: 274 patients underwent local treatment. Median age was 17 years (3-40). 54%of tumors had extremity location, 30% central and 16% pelvis/sacrum. 222 (81%)patients were surgically treated. 70 of them received post operative RT (36 patients dueto inadequate surgical margins). 52 (19%) had RT only. 24 (9%) patients had localrecurrence (with distant metastases in 10). The median time to LR was 15.2 months(6-47). Overall, 5-year probability of local recurrence-free survival (5y-LRFS) was87.5%; 89% for patients who received only S, 93% in case of S+RT and 76% withRT only (p<0.02).The quality of surgical margins did not influence local control(5y-LRFS: inadequate: 92%; adequate: 91%, p=0.4) nor did the histologic response(5y-LRFS: GR 93%, PR 89%, p =0.7). Site of tumor, age, sex, serum LDH did notinfluence local control.

Conclusions: These data confirm that surgery is the main option for local treatmentof ES. RT is an effective adjuvant treatment in case of inadequate surgical margins.With RT only a higher risk of LR can be expected.

Further studies should evaluate whether the addition of RT in patients withadequate surgical margins could improve local control.

D35 AN ATTEMPT TO CORRELATE ‘‘COMPREHENSIVE GERIATRICASSESSMENT’’ (CGA), TREATMENT ASSIGNMENT AND CLINICALOUTCOME IN ELDERLY CANCER PATIENTS: RESULTS OF APHASE II OPEN STUDY

Elena Massa, Clelia Madeddu, Giorgio Astara, Michela Pisano, Carla Spiga,Francesca Maria Tanca, Eleonora Sanna, Ilaria Puddu, Elena Patteri, GiovannaLamonica Laura Deiana, Giovanni MantovaniDepartment of Medical Oncology, University of Cagliari




ownloaded from


Objectives: To assess the correlation of the different CGA categories with differenttreatment administered and clinical outcome. The ultimate goal was to verify whetheran appropriate treatment given to elderly cancer patients according to their CGAcategory could translate into a better clinical outcome, i.e. objective clinical response,performance status (ECOG PS), and toxicity.

Design: Phase II open, prospective non randomized study.

Setting: Inpatients (University Hospital) PARTICIPANTS: 114 elderly cancer patientshospitalized at Department of Medical Oncology, University of Cagliari, Italy.

Intervention: Patients were assigned to 3 different CGA categories: fit, intermediateand frail. Therefore, an appropriate treatment was administered and the clinicaloutcome was assessed.

Measurements: All patients underwent CGA evaluation. The clinical outcome after 3month treatment was defined as objective clinical response, ECOG PS and toxicity. Thedifference of clinical outcome variables between the CGA categories were assessed byANOVA test. Moreover, the correlation of clinical response with CGA category, ECOGPS, stage and dose intensity was evaluated by Spearman’s t test.

Results: A better clinical response was observed in fit patients as compared both tointermediate and frail patients. Treatment toxicity was significantly worse forintermediate patients as compared to fit and frail patients. The correlation analysisshowed a significant direct correlation between clinical response, CGA category anddose intensity; then, the multivariate regression analysis showed that the onlyindependent predictive variables of clinical response were CGA category at baseline anddose intensity.

Conclusion: The main conclusion of our study is that the CGA category is the only trueindependent variable predictive of clinical outcome, as the other variables (doseintensity and ECOG PS) are correlated to it. The most relevant interest of the study isthe new approach in the use of CGA.

D36 RANDOMISED PHASE III CLINICAL TRIAL TO EVALUATE THEEFFICACY AND SAFETY OF AN INTEGRATED TREATMENT (DIET,PHARMACO-NUTRITIONAL AND PHARMACOLOGICAL) IN CANCERPATIENTS WITH CANCER-RELATED ANOREXIA/CACHEXIA ANDOXIDATIVE STRESS: INTERIM RESULTS

Clelia Madeddu1, Giulia Gramignano1, Roberto Serpe1, Elena Massa1, MarieleDessI1, Francesca Maria Tanca1, Eleonora Sanna1, Laura Deiana1, Paolo Contu2,Carlo Floris3, Vittorio Mascia4, Antonio Maccio1 and Giovanni Mantovani1

Department of Medical Oncology1 and Department of Hygiene and PublicHealth2, University of Cagliari, Division of Medical Oncology 23 and 34,OspedaleOncologico Regionale ‘‘Businco’’, Cagliari, Italy

In April 2005 a phase III randomised study was started to establish which was the mosteffective and safest treatment of CACS/OS able to improve identified primaryendpoints: increase of LBM, decrease of REE, increase of total daily physical activity,decrease of IL-6 and TNF-a and improvement of fatigue. All patients were given asbasic treatment: poliphenols + antioxidant agents alpha lipoic acid, carbocysteine,Vitamins E, A and C, all orally. Patients were then randomised to one of the following 5arms: 1) Medroxyprogesterone Acetate (MPA)/Megestrole Acetate (MA); 2)Pharmaco-nutritional support containing 2 g EPA; 3) L-carnitine; 4) Thalidomide; 5)MPA/MA + Pharmaco-nutritional support + L-carnitine + Thalidomide. Treatmentduration 4 months. The sample size was 475 patients. At January 2007, 125 patients,well balanced for all clinical characteristics, have been included. No severe side effectswere observed. As for efficacy, an interim analysis on 125 patients showed animprovement of at least 1 primary endpoint in arm 3, 4 and 5, whilst arm 2 showeda significant worsening of LBM, REE and MFSI-SF. The ANOVA test comparing thechange of primary endpoints between arms showed a significant improvement of REEin favor of arm 5 versus arm 2 and a significant improvement of MFSI-SF in favor ofarm 1, 3 and 5 versus arm 2. The t-test for changes confirmed the worsening of of LBM,REE and MFSI-SF in arm 2 versus arms 3, 4 and 5. The interim results obtained so farseem to suggest that the most effecive treatment for CACS/OS should be a combinationregimen: however, the study is still in progress and the final results should confirmthese data.Work supported by: MIUR National Research Project No. 2006067295

D37 ZOLEDRONIC ACID/DOCETAXEL COMBINATION INHORMONE REFRACTORY PROSTATE CANCER PATIENTS ZANTESTUDY

G. Facchini2, M. Caraglia1, G. S. Bruni2, G. Nasti2, P. Maiolino3, M. Marra1,L. Gallo�, A. Bochicchio*, A. Budillon1, R. V. Iaffaioli22Oncologia Medica B, 1Farmacologia Sperimentale, 3Farmacia ed �Urologia -INT ‘‘G.Pascale’’ – Napoli. *Oncologia Medica – Rionero in Vulture

Background: Docetaxel (DTX) is the standard chemotherapy and Zoledronic Acid(ZOL) is an important therapeutic option in the treatment of advanced hormone-refractory prostate carcinoma (HRPC) patients. Our in vitro preliminary data onprostate cancer cells suggested that ZOL and DTX are synergistic on the growthinhibition of these cells and the synergism is sequence-dependent. Prostate cancer isa suitable target for a pharmacological combination between DTX and ZOL. On the

basis of these considerations a phase I-II trial was designed to evaluate: sequence, DLTand MTD of the combination.

Materials: Escalating doses of DTX in combination with a fixed dose of ZOL (2mg)were administered every 14 days. The following two different sequences ofadministration were explored: Sequence A: DTX day 1 followed by ZOL at day 2.Sequence B: ZOL day 1 followed by DTX at day 2. The first dose level of DTX was 30mg/m2 with a programmed dose escalation of 10 mg/m2 for each level until 50 mg/m2.Serum and PBMC were also collected at each cycle.

Results: To date the MTD was not achieved. We have reached the second level (40 mg/m2) without recording treatment related toxicities. Interestingly, less haematologicaland gastrointestinal toxicities have been observed in one sequence. A different patternof modulation of circulating angiogenic factors (interleukin 8 and 12, VEGF, PDGF),cytokines (TNF alpha, IFN gamma, interleukin-6 and 4) and gamma/delta Tlymphocyte subpopulation are been recording in both sequences of administration.The study is still ongoing and further results will be presented at AIOM meeting.

D38 FOTEMUSTINE AS RESCUE THERAPY IN RECURRENT ORPROGRESSIVE GLIOBLASTOMA AFTER FIRST-LINETEMOZOLOMIDE CHEMOTHERAPY

Ivan Lolli1, Rosa Divella1, Giovanni Silvano2, Simona Finamore1, Letizia Ercolino1,Michele Ronco1, Pasqualino Ciappetta3, Giuseppe Troccoli11Chair and U.O. Clinical Oncology, 3Neurosurgery, University and AzOspedaliera Policlinico Consorziale, Bari, 2 U.O. Radiotherapy, Az Ospedaliera,Taranto/1

Objectives: Glioblastoma multiforme (GBM) care is surgery followed by radiotherapy(RT) plus temozolomide (TMZ) chemotherapy. At the recurrence no standardchemotherapy is actually available. Fotemustine is a third-generation nitrosourea withhigh brain permeability coefficient. The aim of the present study was to evaluateefficacy and toxicity of fotemustine as rescue therapy in patients with histologicallyconfirmed GBM, recurring or progressing, after loco-regional treatment and first-lineTMZ chemotherapy.

Patients: 23 pts (median age 54,2 years (range 28-72,5); median KPS 80) wereconsidered eligible. After surgery, 14/23 pts were recurred or progressed after RT plusconcomitant and adjuvant TMZ first-line chemotherapy, 9/23 pts after RT plusadjuvant TMZ. The primary end-point was progression-free survival at 6 months.Treatment consisted of fotemustine induction infusion (100mg/m2 days 1,8 and 15)with five weeks rest. If pts responded or were stabilized at magnetic resonance imagingcontrol (MRI), fotemustine was continued at the same dose every three weeks until theprogression.

Results: The median time to progression (TTP) was 4 months; the median survival was6 months for all pts.

The progression-free survival (PFS) 6-12 months was 31.8% and 9% respectively;overall survival (OS) 6-12 months was 59% and 13% respectively.

PFS-6 for 14/23 pts with RT plus concomitant and adjuvant TMZ was 28.57%;median time to progression was 17 weeks. Three partial responses (PR) (13.6%) andnine stable diseases (SD) (40.9%) were obtained.

Main toxicity was haematologic (leucopenia and, above all, thrombocytopenia).

Conclusions: Fotemustine seems active and no-cross resistant in pts with GBMrecurrent or progressive after TMZ-based chemotherapy.

D39 TEMOZOLOMIDE AND RADIOTHERAPY FOR THE TREATMENTOF GLIOBLASTOMA: EXPERIENCE OF ‘‘OSPEDALE DI CIRCOLO’’IN VARESE (ITALY)

Pinotti G; Martinelli B; Bandera M; Marelli M; Oriani AOncologia Medica – Ospedale di Circolo & Fondazione Macchi; Varese (Italy)

Background: Glioblastoma (GBL), the most common primary brain tumour in adults,is usually rapidly fatal. The new standard care for newly diagnosed GBL is surgicalresection to the feasible extent, followed by radiotherapy plus concomitant dailytemozolomide (TMZ), and afterwards by 6 cycles of adjuvant TMZ. Epigeneticsilencing of the MGMT DNA-repair gene by promoter methylation compromises DNArepair and has been associated with longer survival in patients with GBL who receivealkylating agents, such as TMZ.

Methods: Patients with newly diagnosed, histologically confirmed GBL were treatedwith focal radiotherapy (daily fractions of 1,6-2,1 Gy given 5 days/week for 6 weeks, fora total of 50- 64 Gy) plus continuous daily TMZ (75 mg/m2/day for 7 days/week fromthe first to the last day of radiotherapy), followed by 6 cycles of adjuvant TMZ (150 to200 mg/m2/day for 5 days every 28). We also tested the relationship between MGMTsilencing and patients’ survival.

Results: We treated 20 patients (median age = 54): 14 patients had undergonedebulking surgery, 6 only biopsy. Median overall survival was 18 months; 1- yearsurvival was 77%, 2-year survival 25%. Concerning progression-free survival (PFS),only 13 patients were studied (2 patients had not completed therapy for toxic effectsand 5 patients had not reached the evaluation times): the median PFS was 9 months;1- year PFS was 20%. At a medium follow-up of 2 years the median overall survivalof patients with MGMT promoter methylation wasn’t reached(1- and 2- year overall




Dow

nloaded from


survival were both 66%); while the patients without the methylation had a medianoverall survival of 14 months, and 1- and 2- year overall survival were respectively 66%and 0% (H.R. = 0,33; p = 0,27).

Conclusions: In our data MGMT promoter methylation seems to be a prognostic andpredictive factor for patients treated with alkylating agents, but we need a largernumber of patients to confirm its role.

D40 PROGNOSTIC ROLE OF CHROMOGRANIN A EXPRESSION FORDOCETAXEL RESPONSE IN METASTATIC HORMONE-REFRACTORYPROSTATE CANCER (HRPC)

Angela Gernone*, Senia Trabucco•, Vincenzo Pagliarulo, Giuseppe Troccoli*,Arcangelo PagliaruloMedical Oncology Unit*, Anatomopathology Unit II• and Urologic Unit, Universityof Bari, Policlinico, Bari

Introduction: The neuroendocrine (NE) cells in prostate cancer are indistinguishablefrom non-NE cancer cells morphologically. We analyzed the expression ofChromogranin A (Chr A) in malignant prostate tissue as prognostic factor forDocetaxel response in metastatic HRPC.

Patients and methods: From January 2003 to December 2006, 39 patients withmetastatic HRPC received a median of 14.2 cycles (range 2-18) of Docetaxel 75 mg/mqevery 21 days and 5 mg of prednisone twice daily as initial therapy. Tissue blocks fromprimary prostate cancer tissues were obtained and immunostaining for Chr A wasperformed. The median age was 70 years (range 46-82); median baseline PSA: 310ng/ml (range 0.15-700); median ECOG P.S.: 1 (range 0-2). PSA level was measuredevery 4 weeks. TTP with Docetaxel was the preliminary end point.

Results: Response to Docetaxel was assessed every 3 cycles of treatment. The Chr Aexpression was found in 19/39 patients with Gleason ‡ 7, PSA < 20, bone and soft tissuemetastasis; 10 of them showed PR (decrease in PSA < 50%), 4 SD and 5 patients PD.TTP was 4.12 months and patients were resistant to different lines of chemotherapy.The PSA level was not correlated with clinical outcome. Instead, Chr A was notdetected in 20/39 patients with Gleason ‡ 7, PSA > 20 and bone metastasis; 12 of themshowed CR (PSA-decline > 50%) and 8 PR, TTP was 10.13 months.

Conclusions: NE differentiation does not constituite a different histopathologicalcategory of prostate cancer but the NE phenotype can be present as a subgroup capableof producing ectopic hormonal substances. NE differentiation can be considereda factor affecting prognosis and treatment in advanced prostate cancer. Cases with ChrA expression did not benefit from Docetaxel and had poor prognosis. Thesepreliminary data indicate that initial therapeutic approach should be differentaccording the presence or absence of Chr A.

D41 HYPOFRACTIONATED SIMULTANEOUS INTEGRATED BOOSTTOMOTHERAPY IN LOCALIZED PROSTATE CANCER: PRELIMINARYTOXICITY RESULTS

C. Cozzarini;1N. Di Muzio1; F. Alongi1; C. Fiorino2; A. Chiara1, P. Zucchinelli4;S. Broggi 5; P. Mangili5; A. G. Guazzoni6;Calandrino5; F. Fazio1-2-3

1Department of Radiation Oncology; 2Department of Nuclear Medicine,Scientific Institute San Raffaele ; 3IBFM-CNR-University of Milano-Bicocca,Milano, Italy; 4Department of Medical Oncology, Scientific Institute San Raffaele,Milano; 5Medical Physics, Scientific Institute San Raffaele, Milano; 6Departmentof Urology, Scientific Institute San Raffaele, Milano

Purpose: To report early toxicity results of a phase I-II study using a moderatelyhypofractionated simultaneous integrated boost (SIB) approach delivered with HelicalTomotherapy (HT).

Material and methods: Between January 2006 and January 2007, 40 patients withlocalized prostate cancer(PC) were treated with HT: data on acute toxicity wereavailable. Different targets (PTV) were defined: Pelvic nodes; 2/3 cranial portion ofseminal vesicles; lower third of SV; prostate. Different doses to each PTV, accordingwith a grouping risk based on NCCN criteria, were delivered in 28 fractions . Clinicaland treatment data were reviewed. Gastro-intestinal (GI) and genito-urinary (GU)signs and symptoms were evaluated according to the RTOG toxicity scales. The medianfollow up time was 257 days.

Results: Of the 40 pts, 15 (37.5%) presented G1, 7(17.5%) G2, and 1(2.5%) G3 acuteGU toxicity respectively. The median time to toxicity was 27 days and 22 daysrespectively for G1 and G2/G3 sequelae. Rectal G1 toxicity (mainly proctitis) occurredin 15 (37.5%) pts. No patients experienced G2-G3 acute side effects. Median time toproctitis G1 was 32 days (18-72days). Only 5 pts(12.5%) showed G1 upper GI toxicity(1 of them received treatment on pelvic limph nodes) with a median time to event of33 days (18-72). None experienced G2-G3 upper-GI toxicity. At last F-up no patientspresented any late toxicity and all patients were assessed to be bNED .

Conclusion: These results suggest that moderately hypofractionated high dose HT isfeasible and safe. No pts with acute rectal toxicity greater than G1 were observed, dueprobably to the excellent sparing of the rectum outside PTV. At the same time acuteGU toxicity is comparable with other published study of high dose IMRT. Furtherfollow up is needed to assess late toxicity and tumor control outcome.

D42 GEMCITABINE (G) AND CISPLATIN (C) WITH CONCURRENTIRRADIATION (XRT) AFTER TRANSURETHRAL RESECTION (TUR)FOR THE CONSERVATIVE TREATMENT OF INVASIVE TRANSITIONALBLADDER CANCER (ITBC). CLINICAL OUTCOMES AT LONG TERMFOLLOW-UP

Valduga F, Caffo O, Fellin G�, Mussari S�, Graffer U*, Brugnara S, Frisinghelli M,Soini B, Caldara A, Galligioni EMedical Oncology, Radiotherapy� and Urology* Units, S. Chiara Hospital, Trento

Introduction: C and G are powerful radiosensitizers with synergistic activity. A dosefinding trial, with C and G combined with concurrent XRT on 16 pts with T2-4 N0ITBC, was published by our group in 2003 (IJROBP). In this study we present updatedlong-term results of these patients, together with additional data on 10 more pts treatedwith the established G MTD.

Methods: T2-4 N0 ITBC pts received, after TUR, XRT (54 Gy) concurrent with C (100mg/sqm q 3 w) starting on day 1 of XRT. Additionally, pts were treated withconcomitant G (on days 1, 8 and 15 q 3w for 2 cycles), at increasing doses of 200-500mg/sqm for the first 16 pts, and at the fixed MTD of 400mg/sqm on days 1 and 8 for theremaining 10 pts. All pts were re-evaluated after 8 weeks with cistoscopy and biopsy inprevious tumor bed.

Results: from June 1999 and December 2004 26 consecutive pts, median age 68(range 51-80) and good PS (0-1), were treated. Two cases of severe toxicity wereobserved at the dose of 500 mg/sqm (intestinal perforation recovered after surgery in1 pt, death after grade 3 diarrhea untreated at home in the other). We observed grade3 thrombocytopenia in 2 pts. No other significant toxicities were observed. All the25 evaluable pts were disease free at the cystoscopic re-evaluation, independently ofgemcitabine dose. After a median follow-up of 36 months (range 9-83), 4 local relapses(2 superficial, conservatively managed – 2 infiltrating, submitted to cystectomy) and2 distant relapse were observed. Presently 19/26 pts are alive, disease-free and retaintheir bladder without any relevant long-term toxicity.

Conclusions: G + C with concurrent XRT in ITBC appears feasible and well tolerated,up to dose level of 400 mg/sqm with encouraging long-term clinical outcomes.Although the role of G cannot be established, our results are in favour of prospectiveevaluation of this regimen.

D43 SECOND LINE POLICHEMOTHERAPY (PCT) WITHCETUXIMAB PLUS DOCETAXEL IN PATIENTS WITH METASTATICSQUAMOCELLULAR HEAD AND NECK CANCER (MSHNC) AFTERFIRST LINE TREATMENT PCT (CIS/5FU) /RT PROGRESSION

Autori: Cotroneo G, Roda G, Carta A, Nonnis D, Mauri C and Nastasi GA.O. ‘‘Bolognini di Seriate’’ (BG). U.O. Oncologia Medica di Alzano Lombardo(BG)

EGFR is expressed in many solid tumors including SHNC and may be an importanttarget in cancer therapeutics. Cetuximab is a monoclonal antibody to EGFR that hasdemonstrated single-agent activity and with chemotherapy in both preclinical andclinical settings. Docetaxel is the only chemotherapy approvated for second lineMSHNC. We investigated the combination of Cetuximab and Docetaxel in second line,in refractary resistant patients affected by MSHNC treated with RT/PCT as first line.

The objectives is to determine the tumor response rate, duration of response,survival, safety and toxicity and pharmacokinetics (PK) of this combination therapy.Cetuximab was administered as a 400mg/mq during the first weeks followed by 200mg/mq weekly. Docetaxel was administrated of 75mg/mq every 3 weeks. We have10 patients. Patients characteristics are 7 males and 3 females; median age 60 years(range 54y – 68y); median Karnofsky PS 70. 5 patients have achieved a partial response,3 patients a stable desease, 2 patients a progression disease. Median number of cycles is6. Pharmacokinetics analysis shows no interactions of Cetuximab whith Docetaxel.This regimen is very well tolerated with minimal toxicities. The most common gradeIII/IV toxicities are neutropenia 31%, mucositis 18%, fatigue 21% and acneiform rush32%. Cetuximab in combination with Docetaxel is well tolerated and the response ratesuggests clinical activity in the second line setting.

D44 PLACEMENT AND MANAGEMENT OF SUBCUTANEOUSPORTS BY A SMALL AND WELL TRAINED ONCOLOGY TEAM: VERYLOW COMPLICATION RATE COMPARED TO UNSELECTED TEAM

Vincenzo Picece, Maurizio Nicodemo, Francesca Coati, Paola Righetti, AlessiaZardini, Annalisa Terzi, Andrea Giacopuzzi, Marco VenturiniOncologia Medica Ospedale Don. G. Calabria-Sacro Cuore Negrar (VR)

From January 2000 until March 2007, we have laced 490 totally implantedsubcutaneous central venous catheters (ports). All the devices were placed in oncologicpatients by the oncologist team (composed of two physicianas and four nurses) andalso managed by the same specialistic group. The principals neoplastic disease thatneeds the positionation of port were: colorectal cancer (24,6%), breast cancer (17,3%),gynecologic cancer (10,8%), lung cancer (9,4%),esophageal and gastric cancer (7,14%),urologic cancer (6,12), head neck cancer (4,7%). The knowledge of the natural historyof the neoplasm, the therapeutic programme, the stage of disease, the patient’s




ownloaded from


characteristics determined the vein and the site where the device will be positionated.The port’s placements has been performed through a percutaneous route by directpuncture of the left subclavian vein (sopraclav. access 26,1%; subclav. access 34%), theright subclavian vein (sopraclav. access 21,4%; subclav. access 6,93%), the right femoralvein 9,39 %. All the complication were collected prospectively. The majorcomplications recorded were divided in early (during the procedure), and late. Earlycomplications comprised: 5 arterious puncture (1%), 4 pneumothoraces (0,8%). Latecomplications comprised: 7 reservoir’s dislocations (1,4%), 4 pinchs off (0,8%),17 venous thromboses (3,5%), 9 reservoir’s infections (1,8%), 1 catheter’s infection(0,2%), 1 kinking (0,2%), 1 catheter’s thromboses (0,2%). The overall complicationrate was remarkably reduced compared to litterature cases . The low rate of early andlate complications may be related to both the limited number of people involved in theimplantation and management of the devices and to the oncologic skill of the team.

D45 JAW OSTEONECROSIS RELATED TO BISPHOSPHONATETHERAPY: A SEVERE SECONDARY DISORDER

Mario Fiumano1, Sergio Fava3, Elena Collova3, Elisabetta Menatti1, OrnellaFusco1, Eliana Berardi1, Fabio Malugani1, Monica Giordano2, Giovanna Luchena2,Palma Pugliese2, Alessandro Bertolini1

Oncology Unit: 1Ospedale Civile Sondrio, 2Ospedale S.Anna, Como, 3OspedaleCivile, Legnano

Background: Bisphosphonate-related osteonecrosis of the jaws (ONJ), first describedin 2003, is gaining importance due to the increasing indication spectrum ofbisphosphonate therapy. ONJ patients suffering from varying bone defects andsymptoms are extremely restricted in their quality of life. The aetiology of ONJ appearsto depend on multiple factors: period and type of bisphosphonate therapy and traumapaving the way for an invasion of pathogens.

Method: In 3 Oncology Unit (Polo Nord Group) all patients treated withbisphosphonate were evalued for jaw osteonecrosis. A complete history has beenrecorded. All patients underwent clinical and radiographic examination. CT scans andMRI have been performed in selected cases. When ONJ positive, we performed threelevels of therapy, associated or not: medical therapy (antibiotic drugs like penicillin,antimycotics like metronidazole and antiseptic mouthwashes), surgical therapy withcurettage or sequestrectomy and laser bio stimulation.

Results:We registered at least 120 patients treated by bisphophonate in the last 3 years;18 of them developed ONJ. Location of necrosis was mandible and maxilla.Characteristics of patients: median age at presentation of ONJ 65.5 years (range 43-79),M/F 7/11, cancer type: 10 breast cancer, 4 myeloma, 3 prostate cancer, 1 carcinoma ofunknown primary; bisphosphonate: i.v. pamidronate followed by zoledronic acid 5 pts,i.v. zoledronic acid 13 pts; median courses 35 (range 6-76). The treatments of ONJwere: antibiotic 8 pts, partial maxillectomy 2 pts, curettage 8 pts. 13 patientsinterrupted bisphosphonate, on the contrary nobody stopped chemotherapy programbecause ONJ or during its medical therapy. After medical therapy ONJ was: NC 4,, PR3, CR 10, NV 1.

Discussion: ONJ has become an increasing problem and the test of that is the increaseof the relative published case report and case series. Patients had in common that,before signs of ONJ were observed, a local traumatic incidence had occurred. Theyshowed signs of infection which could be remarkably reduced by antibacterialtreatment and surgical therapy.

D46 DOSE-DENSE CHEMOTHERAPY AND THE ONSET OF ANEMIA:NEW INSIGHTS

Manzoni M, Bencardino K, Rovati B, Mariucci S, Oliva EN*, Chatzileontiadou S,Delfanti S, Palmeri S**, Danova MOncologia Medica, Fondazione IRCCS Policlinico San Matteo, PAVIA*Ematologia, Azienda Osp. ‘‘Bianchi Melacrino Morelli’’, REGGIO CALABRIA,**Oncologia Medica, Universita di PALERMO

Background: Filgrastim may play a role in worsening anemia in breast cancer (BC) ptsreceiving intensified Epirubicin (E) + Cyclophosphamide (CTX) (Papaldo P. JCO,2006). Pegfilgrastim doesn’t have a negative impact on anemia when utilized withdarbepoietin alfa (DPO) that exerts a potent anti-apoptotic effect on CD34+ cells,as also shown in myelodysplastic syndromes (Oliva E. Blood, 2006). No data areavailable about the effect of pegfilgrastim on Hb levels in dose-dense CT, withoutprophylactic DPO.

Methods: We studied 38 BC pts; 15 N+ received 4 cycles of adjuvant E 90 mg/sqm +CTX 600 mg/sqm every 14 days. 23 with locally advanced disease received 4 cyclesof primary E 75 mg/sqm + Docetaxel 80 mg/sqm every 14 days. All pts receivedpegfilgrastim 6 mg. Three groups were defined on the basis of WBC: A= <10 x 103/mL;B= 10 to 20 x 103/mL and C= > 20 x 103/mL.

Results: WBC and Hb levels were normal at baseline. All pts received the plannedCT dose intensity. Only 3 pts developed G2 anemia and were excluded from theanalysis, because of receiving DPO. Among the 15 pts treated in adjuvant setting,6 dropped in group A, 6 in group B and 3 in group C. The mean Hb decrease fromthe baseline to the last CT course was – 1.6 g/dL; -1.5, -1.8 and -1.4 in group A, B and C,respectively. In the primary setting, 5 pts dropped in group A, 12 in group B and4 in group C. The mean Hb decrease was -1.5 g/dL; -1.3, -1.4 and -1.8 in group A,

B and C respectively. No statistically significant correlation was found between theHb levels and the degree of leukocytosis.

Conclusions: The availability of new hematopoietic growth factors opened newinsights in the problem of anemia in cancer pts. In this field, pegfilgrastim, even whenutilized without DPO, does not worsen anemia in BC pts treated with dose-dense CT.

D47 ORAL CHEMOTHERAPY: SOMEBODY TO PHONE

V. Roberti; G. Navar; V. Faraone; L. Falconio; R. Di Maro; L. Strino; P. Iazzetta;A. M. Grimaldi and G. CartenIA.O.R.N. A. Cardarelli Division of Oncology, Naples

Modern Oncology tend always more to improve quality of life of cancer patients. A stepforward is represented by the oral, equally effective, anticancer drugs, consentinga home chemotherapy. A recent study, in which our Division participated, showed thatin some cancers, is possible to economize using drugs orally available. To improvequality of life of cancer patients in therapy with oral chemotherapies and to respond tothe needs for treatment continuing, was born a dedicated Call-Center.

The project count on a Call-Center with a dedicated database and with a toll freenumber reserved to patients in therapy with oral chemotherapies.

Call-Center is active from Monday to Friday, 09.00 to 12.00, and is opened to thepublic from 10.00 to 17.00 for the organization of the data and to contact patients.

Patients are registered in the database by the prescribing oncologist. Thereforepatients are periodically contacted to verify their health conditions, and at everydeadline of the scheduled follow up biological parameters are monitored. Patients canuse tool free number to communicate biological parameters or eventual side effects.

Phone operators collect patient’s general informations and biological parameters tosubmit to the oncologist on call, who evaluate if suspend or continue chemotherapy.

Moreover data are statistically elaborated and then archived.This project, according to the national and regional directives, want to reduce the

waiting lists, the health costs, and introduce new systems of home-treatment for somecancer patients, giving them a better quality of life.

From December 2006 until today 35 patients were enrolled in treatment, 31 withCapecitabine and 4 with Oral Navelbine. 124 phone calls arrived to the tool freenumber and 71 were done by operators of our Division Call-Center. For these results,work goes on.

D48 LOCOREGIONAL TREATMENT OF ADRENAL NEOPLASTICMASSES: TRANS-ARTERIAL EMBOLISATION/CHEMOEMBOLISATION/CHEMOTHERAPY (TAE/TACE/TAC) ALONEOR FOLLOWED BY RADIOFREQUENCY ABLATION (RFA)

Roberto D’Angelo*, Guglielmo Nasti, Gaetano Facchini, Alessandro Ottaiano,R. Vincenzo Iaffaioli, Francesco Fiore**Sezione di Interventistica Oncologica, Divisione di Oncologia Medica B.INT ‘‘Fondazione Pascale’’ Napoli

Purpose: Isolated adrenal metastases or their combination with a well-controlledintrahepatic recurrence are preferably treated with surgery. RFA has been proposedwhen resection is unfeasible. Nevertheless, RFA alone has shown unsatisfactoryresponse in patients with large lesions. We report our experience using TAE/TACE/TAC for adrenal metastases >5cm.

Material and methods: From January 2002 to December 2006 we treated seventeenpatients in good performance status. These subjects were non-responding to systemicchemotherapy or progressing after chemotherapy and were not eligible for surgery.There were 2 primitive adrenal Ca and 18 adrenal metastases: 10 from HCC (1 bilateralinvolvement), 4 from lung cancer, 1 from lung carcinoid,1 from prostate glandsarcoma, 1 from pancreatic carcinoma and 1 from colon cancer (bilateral adrenalinvolvement). Superselective catheterisation was done with 3F microcatheter afterselective catheterisation of main adrenal branches. We then embolized the mostevident vessels tributary to the adrenal mass with PVA powder (45-150 mm diameter).TACE (50mg of epirubicin plus 5mL of Lipiodol) was carried out in 4 patientswhile 9 only had TAE therapy. 3 patients were treated with TAC (trans.arterialchemotherapy). RFA was subsequently performed in 6 patients with large residualtumour after TAE/TACE.

Results: we performed helical CT evaluation one month later, to assess responserate. After TAE/TACE + RFA we observed a partial response of the target lesion in6 (35%) patients and a stable disease, in 11 (69%) patients. Clinical benefit wasin >76% of patients treated. Conclusion: locoregional treatment of adrenal metastasisis safe and technically feasible, allowing effective devascularization and positiveshort-to-medium term clinical effects.

D49 PROGNOSTIC ACCURACY OF THE PALLIATIVE PROGNOSTIC(PaP) SCORE IN HOSPITALIZED CANCER PATIENTS (pts)

Marcella Occelli1, Raffaella Pasero*1, Elena Fea1, Caterina Nenna2, GianmauroNumico1, Ornella Garrone1, Cristina Granetto1, Ida Colantonio1, Gianna DiCostanzo1, Abdelamid Heouaine1, Valentina Polla Mattiot1, Milena Gasco1,Ilda Giordano*1, Marco Merlano1




Dow

nloaded from


1Medical Oncology, S.Croce General Hospital, Cuneo (*nurse); 2Medical Onco-hematology, Sulmona- Aquila

Background: Clinicians need accurate information about the prognosis of cancer pts.The PaP score was shown to be an accurate prognostic tool for terminally ill cancer pts(Maltoni et al Cancer 1995). The aim of the present study is to evaluate whether PaPscore may be used as a prognosticator on an unselected cancer pts population,accessing to the oncology department in a general Hospital. If the prognostic value ofPaP score is confirmed in this daily practice pts sample, it could routinely help to selectpts treatment (palliative care or active anticancer therapy).

Patients and methods: All the patients admitted for any reason in our Departmentfrom April to December 2005 were included in the analysis.

The PaP score is based on the following variables: the physicians’ Clinical Predictionof Survival (CPS), the KPS (10 to 20 versus 30 to 100), anorexia, dyspnea, totalwhite blood count and lymphocyte percentage. Each variable is linked to a numericalscore. The sum of scores results in the overall PaP score and it is used to select threedistinct populations: 0 to 5.5 (group A); 6 to 11 (group B) and 11.5 to 17.5 (group C).Additional clinical informations will be considered in the final analysis.

Results: Data were available for 208 consecutive pts, the median age was 63 years(range 21– 86). One-hundred sixty-two pts (78%) were in group A, 37 (18%) ingroup B and 9 (4%) in group C. One-month survival was 87.7% (C.I. 82.6-92.7), 47.2%(C.I. 30.9-63.5) and 20% (C.I. 0-44.7) respectively. The difference among the threegroups was statistically significant (p: 0.00001).

Conclusion: The Pap score was shown to accurately identify three groups of ptswith distinct life expectancy, irrespective of cancer type and of disease stage. Thisinstrument could be used by oncologists when a choice between chemotherapy andsupportive care is not obvious.

D50 EVALUATION OF INTOLERANCE REACTION TO FENTANYLTTS WITH VITAL PARAMETERS MEASUREMENT IN AMONOINSTITUTIONAL ANALYSIS OF 300 UNSELECTED OPIOIDNAIVE CANCER PATIENTS

Marco Ali’1, Antonino D’Agostino2, Carmelo Costa3, Guido Carillio1, Rosa AnnaAiello1, Maurizio Chiarenza1, Sabrina Bagnato1, Giuseppina Fallica1, andMichele Caruso1

1Department of Medical Oncology, Humanitas Centro Catanese di Oncologia,Catania, Italy. 2Department of Radiation Oncology, Humanitas Centro Catanesedi Oncologia, Catania, Italy. 3Pain Control Unit, Humanitas Centro Catanese diOncologia, Catania, Italy

The European Society of Medical Oncology suggests that supportive care should beinitiated during the active treatment phase and the medical oncologist should be expertin the management of symptoms and in the coordination of supportive and palliativecare to accompany the cancer patients after discharging from hospital to home care.Pain is the most common discomfort during the cancer history and occurs in almost90% of patients in advanced stage of disease. It is often not adequately treated becauseof inexperience and unfounded fears of administering analgesic drugs.

The aim of this study was to evaluate the safety of fentanyl TTS in opioid naıvecancer patients by accurately determining vital signs and symptoms during the titrationphase performed in hospital or home help. Different parameters were monitored at6 hour intervals in the first 3 days of fentanyl TTS by regular controls and the use ofpulsoxymeter. All the patients started the analgesic treatment at the basal delivery rateof 25 micrograms per hour. Their characteristics were median age 55 years, M/F ratio120/180, median ECOG PS 2, lytic bone metastases in the majority.

Among 300 evaluated patients, only 20 of them (7%) developed intolerance reactionto fentanyl TTS. Patients that experienced intolerance did not suffer major side effectsrequiring emergency support. Both subjective and objective symptoms revealeda satisfactory safety profile of drug even in unfit patients. Only two case of respiratoryrate reduction to 10 breaths per minute with SatPO2 78% were recorded, withoutrelevant decrease of blood pressure.

Fentanyl TTS is a safe treatment for analgesia of patients with moderate to severecancer pain. Our policy of surveillance during titration phase of drug did not show anymajor side effect. The study supports the use of pulsoxymetry and vital signsmonitoring as essential instrument for assessing the tolerance to drug and reassuringclinician and care giver about the oxygenation validity, also in a home care setting.

D51 HYPOXIA-INDUCED p21(WAF) AND p27 REGULATION INC-MYC IMMORTALIZED CELLS

Di Seri Marisa, Raimondi Cristina, Rosati Maria SofiaDpt of Oncology, University ‘‘La Sapienza’’, Rome, Italy

Background: Hypoxia is an adaptative response to tissue damage whose mechanismshave not been yet characterized. From a clinical viewpoint, tumours with morenecrosis, an indicator of severe hypoxic stress, are often resistant to conventionaltreatment and are associated with poorer prognosis. Moreover, the 65% of tumoursoverexpressed c-myc which strongly enforces proliferation in oxygen deprivedconditions. Evidences showed that c-myc blocked cyclin-dependent kinase inhibitors

(CDKI) through a complex network of interactions to induce proliferation and G0-Stransition.

We examined whether Rat-1 immortalized fibroblasts undergo cell cycle arrestp21waf- and p27- mediated in response to oxygen deprivation.

Materials and methods: c-myc null cells (-/-) were derived by gene targeting from animmortalized but otherwise non-transformed Rat-1 fibroblast cell line. Oxygendeprivation conditions (0.2% O2 and 1% O2) were achieved in a humidified anaerobicworkstation at 37 C for 6 or 24 hours in c-myc (+/+) and c-myc (-/-) samples. Proteinconcentration was determined by the Lawry assay method. Immunoblots for c-mycand p21waf and p27 were performed.

Results: c-myc (+/+) samples collected after 6 hours of hypoxia showed lower p21waf and p27 levels than c-myc (-/-) which were supposed to be slowly proliferating.Over 24 hours of hypoxia, cell cultures are supposed to be oxygen-dependent andwe found higher CDKI levels in c-myc (+/+) cells.Discussion: Our data could explain same resistance mechanisms of tumours cells. Infact, before 6 hours oxygen deprivation, cancer cells are not able to supply autonomousoxygen support (neo-angiogenesis, in vivo) so that c-myc immortalized-cellsdownregulate p21 waf and p27 expression to overcome CDKI cell-cycle arrest. Whenthe cells acquired oxygen dependent growth mechanism, low oxygen level induced c-myc mediated p21 waf and p27 up-regulation to induce cell cycle arrest. Despite theup-regulation of CDKI, PS 341 (proteasome inhibitors) has been demonstrated toinduce apoptosis. Our data kindly encouraging trials on the use of p21 waf and p27stabilizers (like PS 341) in those tumour who are known to overexpressed c-myc.

D52 PEGFILGRASTIM TO SUPPORT CHOP-R CHEMOTHERAPYADMINISTERED EVERY 14 DAYS IN THE PATIENTS (PTS) WITHAGGRESSIVE B-CELL NON-HODGKIN‘S LYMPHOMA (NHL)

E. Capochiani1, S. Cupini1, F. Loupakis1, E. Vasile1, A. Fontana1, C. Barbara1,S. Bursi1, L. Landi1, L. Coltelli1, V. Safina1, MT. Barletta1, GG. Baldi1, N. Giuntini1,M. Lo Dico1, E. Mazzoni1, G. Masi1, A. Falcone1,2

1Division of Medical Oncology, Azienda USL-6, Livorno; 2University of Pisa, Italy

Background: CHOP chemotherapy administered every 21 days has been the standardregimen for treatment of aggressive NHL for many years. Recent studies have shownimprovements in both complete remission and survival following addition ofRituximab to CHOP 21 (Coffier et al, NEJM 2002) and following reduction of the cyclelength of standard 21 day CHOP to 14 days (Pfreundschuh et al, Blood 2004). Previousstudies with CHOP 14 have demonstrated the need of filgrastim to allow theadministration of chemotherapy at planned dose and on time in this setting.

Methods: This study evaluates the feasibility of the combination of CHOP plusRituximab (375 mg/mq) repeated every 2 weeks (CHOP-R 14) supported with a singleadministration pegfilgrastim (6 mg, on day 2) up to six cycles in pts with aggressiveB-cell NHL.

Results: Up today 18 pts have been enrolled. Patients’ characteristics are: medianage 66.5 years (46-73), sex 8M/10F, ECOG PS 0(14), 1(3), 2(1), B symptoms 39%, stageI(1), II(6), III(6), IV(5), extranodal location 4 (22%). Overall 94% of pts receivedfull dose chemotherapy on schedule for all planned cycles (range 4-7). Chemotherapywas delayed and dose reduced in 11% and 6% of pts respectively. Main grade 3-4adverse events per pts were: neutropenia 33%, febrile neutropenia 11%,thrombocytopenia 11%, anemia 22%. One pts died because of treatment related sepsis.Responses at the end of treatment (14 evaluable pts, 4 too early) were: complete 71%,partial 3%. Up today the median follow up is 7.1 months, no pts progressed andmedian RFS and OS have not been reached.

Conclusions: These preliminary results indicate that the delivery on schedule ofdose-dense CHOP-R 14 to pts with previously untreated aggressive B-cell NHL is safeand active with once per cycle pegfilgrastim support.

D53 SURVIVAL PREDICTION OF TERMINALLY ILL CANCERPATIENTS BY CLINICAL AND LABORATORY PARAMETERS:USEFULLNESS ROLE OF SIMPLE PROGNOSTIC INDICATORS

Giovanna Vasini, Gian Paolo Bacchini, Vittorio Franciosi, Cristiana Ghidini,Antonino Musolino, Roberta Camisa, Tiziana Meschi*, Loris Borghi*, AndreaArdizzoniMedical Oncology Unit, * Department of Clinical Sciences, Parma UniversityHospital, Parma, Italy

Background: Although accurate prediction of survival is essential for palliative care, noclinical tools have been established. Aim of this retrospective study was to assess clinicaland laboratory factors predictive of survival in a population of patients with terminalcancer.

Patients and methods: The study cohort comprised 98 advanced cancer patients, nolonger suitable for anticancer therapy, transferred between January 2004 and December2006 from the Medical Oncology Unit to the Palliative Care Unit of Parma UniversityHospital. The analysis was performed for 23 clinical and laboratory parametersevaluated on admission to palliative care ward, including tests for hepatic, renal andhematological functions, presence of symptoms such as dispnoea, anorexia, diarrhea,pain, fever, intestinal occlusion, arithmia, depression, hemorrhage, presence of




ownloaded from


therapies such as opioids, oxygen-therapy, insulin administration, parenteralnutrition.

Results: Median age was 69 years (range 34-93). Tumor sites were: breast (22%);gastrointestinal (21%); lung (20%); head and neck (16%); others (21%). All thepatients had previously been treated with more than 1 line of chemotherapy formetastatic disease. Overall median survival (MS) was 45 days. Seven factors were foundto be indicators of a worse survival by univariate analysis: anorexia (P=0.004); fever(P=0.002); Braden Score (BS) for decubitus risk (<17 vs 3 17) (P<0.001),pseudocholinesterase (p-CHE) (£4.300 U/l vs normal, P<0.001); white blood count(310,000 vs normal, P<0.001); LDH (>500 U/l vs normal, P<0.007); INR (>1.14 vsnormal, P<0.002). Cox regression analysis revealed that only BS (<17 vs 3 17: HR=2.47,95%CI: 1.53-3.99, MS: 30 vs 87 days), p-CHE (altered vs normal: HR=3.28, 95%CI:2.01-5.35, MS: 24 vs 103 days) and LDH (altered vs normal: HR=1.83, 95%CI:1.14-2.97, MS: 25 vs 61 days) were independent predictors of survival.

Conclusions: A cluster of simply assessable clinical and laboratory parameters may beused to accurately predict survival in terminal cancer patients. These prognosticindicators may be useful in the day-by-day therapeutic decision-making process ofpalliative care and medical oncology specialists.

D54 SECOND LINE CHEMOTHERAPY WITH FOTEMUSTINE (FTMS)FOR THE TREATMENT OF PATIENTS (PTS) WITH GLIOBLASTOMAMULTIFORME

A. Paccapelo*, R. Ricciuti, M. Cardinali^, R. Trignani, L. Burattini*, L. Fabbietti^,M. Pezzoli**U.O. di Oncologia Medica; U.O. di Neurochirurgia,; ^U.O. Radioterapia -Ospedali Riuniti Umberto I – Salesi- Lancisi; Ancona

Aim of this retrospective study was to evaluate the toxicity and the effectiveness ofa second line chemotherapy with Fotemustine (FTMS) in 32 pts with histologicaldiagnosis of glioblastoma, progressive after Temozolomide. Period: March 2004-December 2006. Treatment: in 15 pts phase of attack with FTMS mg100/sm day 1-8-15,following phase of maintenance, same dose every 3 weeks, after a rest of 5-6 weeks. In17 pts same schedule without phase of attack, due to old age or prolonged medullarystress from Temozolomide. Patients: M/F. 13/19. Median age 55 years, range 18-76.Karnofsky P.S. >/= 80 in 28/32 patients. All 32 pts pretreated with TMZ, 19 inassociation with Radiotherapy.Results: An overall of 155 cycles have been administered (average 4,8 cycles, range1-11). We reduced the dose of 10-30% in all the patients. Objective Response: 1complete response (CR), 3 minor + partial responses (RP), 13 stable desease (SD)e 14 progressions (PD). Therefore the control of desease is altogether achieved in the55% of patients. Median Progression Free Survival was 4 months, with PFS/6 monthsof 38% and 12/31 patients without progression at this moment. Median OveralSurvival was 6,7 months from the beginning of the treatment with FTMS. MedianOveral Survival from dignosis was of 18 months with 10/32 patients (31%) still alive.

Toxicity: we recorded as grade 4 (NCI CTG) only neutropenia in 1 pts. Other toxicities(grade 1-2): neutropenia in13 pts ; thrombocytopenia in 6 pts ; anaemia in 1 pts;nausea-vomiting in 4 pts, liver toxicity in 2 patients. Six patients had a long periodof light but prolonged thrombocytopenia, that involved the suspension of thetreatment.

Conclusions: the treatment with Fotemustine after progression to the Temozolomide,despite the protracted exposure to chemotherapy in patient previously considered‘‘out of therapy’’, has an excellent profile of tolerability. With this good antitumoractivity and survival times, this therapeutic agent may deserves further studies.

D55 HIGH GRADE SURFACE OSTEOSARCOMA. THE RIZZOLIINSTITUTE EXPERIENCE

Eric L. Staals1, Emanuela Palmerini2, Stefano Ferrari2, Mario Mercuri1, PatriziaBacchini3, Franco Bertoni31Department of Orthopedic Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy;2Department of Chemotherapy, Istituto Ortopedico Rizzoli, Bologna, Italy;3Department of Surgical Pathology, Istituto Ortopedico Rizzoli, Bologna, Italy

Background: High grade surface osteosarcoma represents a distinctive variety ofosteosarcoma arising on the bone surface, accounting for less than 10% of surfaceosteosarcomas .

Design: We studied 25 cases of tumors bearing the histologic features of high grade(Broders’ grade 3 and 4) osteosarcoma and located on the bone surface in 6 women and19 men aged 9-66 years (mean 25 years, median 21 years). Histologic features werereviewed in all cases and radiographs were available for 23 patients.

Results: All 25 lesions involved the long bones of the inferior limb. The most commonsites were: the mid portion of the femur (11 patients), of the tibia (7 patients), andof the fibula (2 patients). Three patients had a lesion of the distal femur and 2 patientsof the proximal tibia. Radiographically the majority of the lesions showed dense tomoderate mineralization (19/23: 83%). Circumferential involvement of the host bonewas on average 87% (range 20% to 100%). Medullary involvement was present in 59%of the patients. The histological aspect was that of a grade 4 osteoblastic osteosarcomain twenty patients, and that of a grade 4 chondroblastic osteosarcoma in five. Lungmetastases were detected at presentation in 5 (20%) patients.

Treatment: Twenty-one patients were managed with a combination of surgery andchemotherapy (13 neoadjuvant, 8 adjuvant). One patient underwent onlychemotherapy, and three patients were managed with surgery alone.

Outcome: The median follow-up was 96 months (range:6 months to 25 years).Four patients died (three of disease, one of unrelated cause), and one patient is alivewith disease. The remaining 20 patients are alive with no evidence of disease.

Conclusions: High grade surface osteosarcoma is the rarest subtype of surfaceosteosarcoma. It has the epidemiology and prognosis similar to that of conventionalcentral osteosarcoma. Wide surgery alone was effective in selected cases. Wide excisionand chemotherapy are associated with better results.

D56 OSTEO-ONCOLOGY CENTER: TWO YEARS OFMULTIDISCIPLINARY CARE FOR PATIENTS WITH BONEMETASTASES

Toni Ibrahim, Laura Fabbri, Rossana Ricci, Emanuela Flamini, Laura Mercatali,Patrizia Serra, Marco Maltoni, Dino AmadoriOsteo-Oncology Center, IRST, c/o Department of Medical Oncology,Morgagni-Pieratnoni Hospital, Via Forlanini 34, 47100 ForlI, Italy

Background: Bone metastases (BM) are responsible for high morbidity in cancerpatients. In January 2005 we founded a multidisciplinary Osteo-oncology Centercomprising 17 specialists, thus offering much needed multidisciplinary care for patientswith BM.

Patients and methods: The objectives of the center are patient care, research andtraining. At the end of March 2007 we had seen 335 patients (135 males and 200females) and carried out 434 multidisciplinary visits with a team of experts in oncology,palliative care, orthopedics, radiotherapy, physiatrics, nuclear medicine and radiology,with backup support from an oncology nurse and data manager.

Results: Of the 335 patients, 45.7% had breast cancer, 17.1% lung cancer, 7.9%prostate cancer, 6.1% colon cancer, 3.4% stomach cancer and 19.8% other cancers.High-risk lesions, uncontrolled pain, and first or uncertain diagnosis of BM were themain reasons for referral to the center. 81.1 % of patients had pain, with a median painintensity of 4 or 5 points (BPI questionnaire), and 57.8 % were taking analgesics.Analgesic therapy was modified in 46% of cases. We prescribed radiotherapy(63 cycles), radiometabolic therapy (13 cycles), radiology interventions (24),preventive orthopedic surgery (6 patients) and orthopedic aids in 46% (145) ofpatients. An anonymous questionnaire completed by patients at the end of the visitshowed that 77.2% were very satisfied with the service provided, 21.7% were reasonablysatisfied, and only 1.1% were dissatisfied.

Conclusions: The high level of satisfaction expressed by patients, together with theimportance of decreasing bone metastasis morbidity and of reducing psychophysicalsuffering in patients re-affirms the usefulness of this model of multidisciplinary care.

D56BIS NARRATIVE MEDICINE IN ONCOLOGY PRACTICE

S. Chelia, F. Focardia, P. Martininoa, F. Velicognab, L. Fiorettoa

aUOC Oncologia Medica – Dip. Oncologia Azienda Sanitaria 10 - Firenze,bInstitute of Consctructivist Psychology - Padova

The effective practice of medicine requires narrative competence, that is, the ability toacknowledge, absorb, interpret, and act on the stories and plights of others. Withnarrative competence, physicians can recognize patients own personal journeysthrough health care. Research reveals that writing about one’s experiences offers anindividual the opportunity to improve function, develop insight, and foster growth.During six months we outlined a narrative project with ten cancer patients. Thepatients were recruited from Oncological Department of S. Maria Annunziata Hospitalin Florence. All participants took part in narrative group meetings twice a month witha trained facilitator. Every one of them told own personal experience and wereencouraged to write about it. The PGWBI1 and the EORTC QLQ-C302 wereadministered before and after the narrative intervention. ANOVA testing fordifferences in PGWBI and EORTC QLQ-C30 did not reveal significant differences inthe two surveys. The patients writings were analyzed by two validated methods:thematic analysis3 and socio-linguistic analysis4. We discuss the thematic and linguisticoutcomes in our research and in cancer literature, pointing out methodologicalproblems and suggestions for further research. It seems fitting that the final wordsshould be from a participant, who illustrates this project as follows: ‘‘It’s veryimportant listening the others: maybe we can find the will and the energy to go onunderstanding human stories’’.

1Dupuy HJ (1984). The Psychological General Well Being (PGWB) Index. In:Wenger NK, et al. Assessment of quality of life in clinical trials of cardiovascular therapies.New York: Le Jacq Publishing Inc.

2Aaronson NK, et al. (1993). The European Organization for Research andTreatment of Cancer QLQ-C30: a quality-of-life instrument for use in internationalclinical trials in oncology. J Natl Cancer Inst, 5:365–76.

3Owen WF. (1984). Interpretative themes in relational communication. Q J Speech,70:274–87.

4Bakhtin MM (1986). The problem of speech genres. In C. Emerson, & M. Holquist(Eds.), Speech genres and other late essays . Austin: University of Texas Press.




Dow

nloaded from


D57 PLASMA VEGF LEVELS IN HEALTHY CONTROLS AND HCCPATIENTS SUBMITTED TO PERCUTANEOUSLY RADIOFREQUENCYTHERMAL ABLATION

Girolamo Ranieri1, Annamaria Catino1, Vito Fazio1, Gianluca Vinciarelli1, MariaCoviello2, Michele Quaranta2, Giuseppe Laricchia1, Vittorio Mattioli3, CosmoGadaleta1

1Interventional Radiology Unit, 2Department of Experimental Oncology,3Department of Clinical Area and Surgery; Istituto Tumori Giovanni Paolo II, Bari

The study aims to assess the plasma (P) P-VEGF levels in 20 healthy controls and35 hepatocellular cancer (HCC) patients before and after percutaneouslyradiofrequency thermal ablation (PRFA), respectively. Enrolled patients showed: singlelesion with a maximum diameter of 3.5 cm, no lymphnodal involvement and/ormetastatic disease, no main portal vein thrombosis, no ascites, adequate liverfunctional reserve, A or B status according to Child-Pugh’s classification. PRFAprocedure was performed by using partially insulated needle electrodes (17.5 gauge;Tyco-Hospital Service, Pomezia Italy) placed under ultrasonographic guidance into thetumour to be ablated that inducing coagulative necrosis. In healthy volunteers and inHCC patients samples of blood were taken before, 2 and 5 days after PRFA respectively.Venous blood was dispensed into a into a sodium citrate, theophylline, adenosine,dipyridamole tubes for P (Becton Dickinson Hemogard Vacutainer Systems,Plymouth, UK). P samples were centrifuged at 180 x g x 10 min. The supernatant ofP was removed obtaining a platelet-rich plasma P-RP. After removing the supernatant,the samples were again centrifuged at 1500 x g x 15 min to obtain a platelet-poorplasma P-PP. P-RP was treated with thrombin (Hemoliance Q.F.A. Thrombin Bovine)(80 ll/ml) obtaining a aplasma activated platelet rich P-APR. VEGF levels wereexamined in all the above P fractions using the Quantikine Human VEGF-ELISA R&DSystems Inc, Minneapolis, MN). A statistical significantly differentiation betweenhealthy controls and HCC patients in VEGF level per platelet count was found (meanvalue: 1,6 pg/106 vs 0,3 pg/106 p=0.003 by t-test) suggesting that platelets VEGF myplay a role in HCC angiogenesis. Furthermore no significant difference was foundbetween pre- and post- VEGF levels in HCC patients. We think that P-VEGF level isnot useful as early predictive marker of response to PRFA.

D58 SECOND-LINE NAVELBINE PLUS ESTRAMUSTINE AFTERTAXOTERE IN HORMONE-REFRACTORY PROSTATE CANCER

Perroni D, Paze EOncologia ASL 17 Saluzzo

First line taxotere (TXT) has shown some benefit vs mitoxantrone alone in hormone-refractory prostate cancer (HRPC) in phase III trials. On the other hand patientsprogressing after first-line chemotherapy are poorly investigated and only supportivecare is often offered in this elderly and unfit population. Vinorelbine (NVB) is active inHRPC and shows a good toxicity profile. As NVB estramustine (EM) is a microtubuleinhibitor with distinct molecular targets which shows lack of cross-resistance andnonoverlapping toxicities. The purpose of this study is to investigate the activity(decrease >50% of PSA and clinical benefit lasting > 8 weeks) and safety of NVB+EM,according the schedule of Hoosier Oncology Group, in patients (pts) progressing afterfirst line TXT. From January 2006 14 consecutive pts has been enrolled and 13 of themare now evaluable for toxicity and 9 for serological activity. Median age 70 y (range 52-83), PS 1 (range 0-2 ), basal PSA 499 (range 19-2034). Two of them had local relapse, 2pts lymphnode mets with local relapse, while 6 pts had bone mets and 2 pts rising PSAalone. Main symptoms were pain (7 pts) and asthenia (8 pts). To date 174 bolus NVBhave been delivered (median 12,5 – range 2-33). G1-3 nausea (5 pts ) and G1-3 anemia(11 pts) were the commonest toxicities. One pt had to stop EM due to vomiting and another one stopped EM+NVB due to herpes zoster, 2 pts required blood transfusions,while 3 pts were treated with epoietin for anemia. Four of 9 evaluable pts met the abovementioned PSA response criteria (44%), two of them were TXT-refractory (noserological response to first-line TXT). The response lasted from 8 to 18 weeks.Two more pts (22%) showed lower PSA decrease lasting >8 weeks.

So far this regimen seems to be safe and has shown a good activity, even inTXT-refractory pts.

Updated results will be given at the time of the congress.

D59 QUALITY OF LIFE IN HOME PARENTERAL NUTRITIONCANCER PATIENTS

E. Agnello, F. Rahimi, M. Scigliano, T. Monge, C. Finocchiaro, E. Milanesi1,P. Racca1

A. Palmo, Clinical Nutrition Unit ASO S. G. Battista Turin, 1Medical Oncology-CURO ASO S.G. Battista Turin1

Background: Indication for HPN in advanced cancer patients (ACP) is still hard todefine. Besides clinical and prognostic factors, quality of life (QoL) during treatment isone of the most important items to consider.

Objective: To evaluate the effect on QoL in ACP pts included in HPN with thecurrently accepted criteria.

Methods: ACP were included in HPN according to the following criteria: oral intake£75% of BEE and contraindication or intolerance to enteral nutrition, life expectancy ‡

2 months, Karnofsky Index (KI) ‡50, control or absence of pain, absence of severeorgan alterations. The results of the first 38 consecutive pts (22M/16F) are reported.Site of primary tumor: oesophagus/stomach (10 pts), lung and colon (4 pts each),retroperitoneum and other (3 pts each), pancreas and uro-genitals (2 pts each). HPNindications: sub-obstruction: n 20; malnutrition: n 18. Nutritional status, IK and QoL(EORTC-30) were assessed at the beginning and after 1 month of HPN. Statisticalanalysis: t-test for paired data.

Results: Baseline values (median/range) of KI: 70 (50-80), Body Weight: 56 (37-73) kg,Body Mass Index: 20 (13-29) kg/m2, Subjective Global Assessment: B= n19; C= n19,and s-Albumin: 3.6 (2.1-4.5) g/dL did not change significantly during the study. Severalfactors of QoL significantly improved: fatigue (p=.011), nausea/vomiting (p=.0046),and dyspnea (p=.0012) decreased; appetite (p=.00047), global health status (p=.0028)and global QoL status (p=.02) increased. Other items (emotional, cognitive and socialfunctioning, pain, insomnia, constipation, diarrhoea and financial difficulties)remained unchanged, while physical (p=.0025) and role functioning (p=.0049)significantly worsened.

Discussion: This study suggests that 1-month HPN may maintain or significantlyimprove all EORTC-30 items, except physical and role functioning, if current inclusioncriteria are met and nutritional status remains unchanged.

D60 THREE CASES OF ACUTE RENAL FAILURE (ARF) DUE TONON-HODGKIN LYMPHOMA INFILTRATION OF THE KIDNEYS (LIK)

Alessandro Del Conte1, Vincenzo de Pangher Manzini1, Manuela Bosco2,Giuliano Boscutti2

SOC di Oncologia1,SOC di Nefrologia ed emodialisi2Ospedale di Gorizia

Background: Renal involvement is a relatively common finding in non-Hodgkin’slymphoma (NHL), but ARF due to LIK has been described infrequently.

Materials:We reviewed all the patients with the diagnosis of NHL observed in Oncologyand Haemodialysis departments. In three cases the clinical presentation was ARF.

Results: Case 1: a 75-year-old woman presented with angina, weakness and ARF(creatinine 6.0 mg/dl). Ultrasonography (US) showed enlarged and hyperechogenickidneys and the renal biopsy revealed NHL infiltration. The patient died a week afteradmission to the hospital and the autopsy proved diffuse infiltration of NHL, inparticular bilateral massive renal involvement. Case 2: a 78-year-old man presentedwith generalized malaise, pleural effusion, diffuse lymphoadenomegaly and ARF(creatinine 6.3 mg/dl). Computerized tomography scan (CT) did not display anyalterations of kidneys. Three days after the patient died. The autopsy revealed diffuselymphoadenomegaly caused by centroblastic/centrocitic NHL with massive infiltrationof the kidneys. Case 3: a 69-year-old-man patient with a progressive elevation of serumcreatinine (5.1 mg/dl), anaemia and thrombocytopenia. Clinically emerged hepato-splenomegaly without adenopathy. The bone marrow biopsy was suggestive for mantlecell NHL. Renal biopsy displayed a small lymphomatous infiltration of the fat aroundthe kidney. No sign of urinary obstruction. The patient was treated firstly with 2 cyclesof high dose steroid plus vincristin, then with 6 cycles of HyperCYVAD chemotherapyplus Rituximab. The renal function recovered. The FDG-PET/CT scan after the 6th

cycle showed a complete remission of NHL, but revealed the appearance of a gastricneoplasia with hepatic massive metastasis (adenocarcinoma at gastric biopsy).

Conclusions: In our experience the ARF due to LIK is suggestive for high tumourburden with a very poor prognosis. But, if we make a diagnosis when the tumourburden is limited (case 3), we could perform the chemotherapy and cure the patientsfor NHL, even if the first sign of presentation has been an ARF.

D61 TREATMENT WITH BISPHOSPHONATES: PREVENTION OFOSTEONECROSIS OF JAW IN PATIENTS WITH BONE METASTASESFROM SOLID TUMORS

A. M. Vandone1, M. Scoletta2, M. Ardine3, M. Donadio1, A. Beano1, A. Polimeni1,R. Spadi1, I. Chiappino1,D. Ottaviani1, A. M. Marra1, L. Ciuffreda1

1Medical Oncology - C.O.E.S. and )Oral Surgery I, San Giovanni BattistaHospital, Turin and 3Medical Oncology –, Carmagnola ASL 8

Recently, use of bisphosphonates in oncology have been discussed because of thesignificant complication related to the treatment with such agents: the osteonecrosis ofthe jaw (ONJ). ONJ is considered a serious event that can adversely affects the qualityof life of patients with significant morbidity too. In our institution, ONJ cases were 9,the first one in June 2004. The last diagnosis of ONJ was in March 2006. Weconsider the prevention activity of ONJ that we do in our Institution very important,effected with the collaboration between Oncologists and Oral Surgeons. From October2005 we have change our attitude, with the creation of an Interdisciplinary Group ofCare for the evaluation of patients who have to start the treatment withbisphosphonates and for their monitoring during therapy. Each patient undergoesa basal oral examination and a panoramic radiography. To minimized the risk ofdeveloping ONJ, the beginning of therapy is delayed until oral conditions areoptimized with the extractions of non-restorable teeth and those with a poor prognosis.We also actuate dental prophylaxis, caries control and conservative restorativedentistry. For patients with full or partial dentures, we examine for areas of mucosaltrauma. We educate patients to the importance of dental hygiene and regular dentalevaluations. We also give an information letter for the dentist in charge, an effective




ownloaded from


way to improve ONJ awareness. From the beginning of this activity, we have evaluated112 patients with bone metastases from solid tumors: in about 50% of cases those werepreventive visits before treatment starts and everyone, immediately or after necessarydental cares, obtain the indication to bisphosphonates therapy. In this group, 40% ofpatients have bone metastases from prostate cancer and 50% from breast cancer. Wenot observe other new ONJ cases in the last 12 months. This appeares a goodorganizational model for a more controlled and sure use of bisphosphonates inoncology.

D62 IMMUNOMODULATING PROPERTIES OF BUPRENORPHINE INCANCER PATIENTS

Giovanni Scambia1, Andrea Fattorossi1, Alessandra Battaglia1, Ida Paris2, M.Claudia. Masi2, Gabriella Ferrandina1, Adriana Mascaro3, Vanda Salutari11Gynecologic Oncology Unit, Catholic University of the Sacred Heart, Rome.2Department of Oncology, Catholic University of the Sacred Heart,Campobasso. 3Department of Anesthesia, Catholic University of the SacredHeart, Rome

Background: Transdermal buprenorphine, a potent opioid analgesic, is used in cancerpain therapy. Since cancer cells have the capacity to elude immunosurveillance andopioids display immunomodulatory effects likely mediated by receptors onimmunocytes, their use should be carefully managed. However, previous animalstudies have shown that buprenorphine is devoid of intrinsic immunosuppressiveactivity. Aim of the study was to assess efficacy, safety and immunomodulatorypotential of transdermal buprenorphine in cancer patients(pts).

Methods: A phase IV prospective study was planned with accrual of 26pts on pain(visual analogue scale, VAS, ‡60mm). Buprenorphine was administered at startingdose of 35 lg/hr q72h. Primary efficacy measure (VAS), safety and immune propertieswere assessed at basal, 1 and 2 months after treatment. Evaluation of peripherallymphocyte subsets was performed by flow cytometry. T-lymphocyte mitogenresponsiveness was assessed.

Results: At present 16/26 pts (3endometrial, 1breast, 3ovarian, 4cervical, 1vulvar,2lung, 1liver and 1pancreatic cancers) have been evaluated for efficacy and safety.Efficay was verified on 50% of pts with mean reduction of VAS to 30mm. In 18% a doseincrease was required. Analgesic drugs were added to buprenorphine in 37.5% of pts,after a mean time of 2 months, due to tumor progression. Adverse events generallytypical of opioids were observed in 3pts (G3 nausea in 2pts, G2 allergic reaction in 2pts,dizziness in 2pts). Basal blood cell and CD3+-lymphocyte counts were within normalvalues and did not significantly differ from subsequent time points. Buprenorphine didnot significantly affect the lymphocyte subpopulations studied. However, NK-lymphocytes and Treg were fairly decreased (from 167 to 34 and 103 to 41cells/ll,respectively), whereas TC1 and TH1-lymphocytes were permanently weakly increased(from 3.4 to 13.8 and 0.76 to 3.2cells/ll, respectively). Buprenorphine did not alterCD4+ and CD8+-lymphocytes functional properties.

Conclusions: Transdermal administration of buprenorphine provides satisfactoryanalgesia, is well tolerated and does not affect the main peripheral lymphocytesubpopulation distribution in cancer pts.

D63 BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAW(ONJ): GORIZIA EXPERIENCE

Roberta Perlazzi1, Alessandro Del Conte1, Liliana Foghin1, Claudia Sfiligoi2,Giulio Tamburini2, Piero Pellegrini3, Vincenzo de Pangher Manzini1,SOC di Oncologia1. Servizio di Odontostomatologia2. Dipartimento diDiagnostica per immagini3. Ospedale di Gorizia

Background: ONJ is an emerging adverse event that can heavily deteriorate the qualityof life in cancer patients treated with bisphosphonates for bone lesions. At the moment,the right incidence and the best therapy of ONJ remain not fully known.

Materials: Between October 2004 andMay 2006 we observed 7 cases of ONJ. We reportour experience about diagnosis and treatment of ONJ in these patients and, moreover,about the institution of a multidisciplinary group and the results of a prophylaxisprotocol.

Results: The seven patients (4 women, age between 57 and 84 years) were affected bybreast carcinoma (3 cases), prostate (2), multiple myeloma (2). The median number ofIV bisphosphonate administrations has been 25, but ONJ developed after a variablenumber of administrations (6-47). In 6 patients there were adjunctive local risk factorslike extraction or oral surgery. There was not any correlation with the type ofchemotherapy or hormonotherapy, and there was a broad spectrum of clinicalpresentation (from the subclinical one to Ludwig angina). In all cases there was anexposed bone of the maxillofacial region that was treated with antibiotic therapy andsurgical debridement. Two patients required also hyperbaric oxygen treatment(without success). The osseous healing was reached in 4 cases after spontaneous orsurgical removal of bony sequestrum. Radiologically (orthopantomography, RNM,TAC, dentalscan, bone scan) there were only non specific signs that did not alwayscorrelate with clinical healing. To confront this new relevant problem and to preventONJ, in May 2006 we created a multidisciplinary group (oncology,odontostomatology, radiology). From that data all patients eligible for bisphosphonatetherapy are submitted to a preventive oral examination and complete all invasive dentalprocedures before bisphosphonate.

Conclusions:. In our experience, the ONJ developed independently from the durationof bisphosphonate therapy but in correlation with invasive dental procedures. Mostimportantly, after the institution of a prevention plan we did not observe other newcases of ONJ.

D64 DEVICES PORT FOR CENTRAL VENOUS ACCESS (CVAPDS) INCANCER PATIENTS PERFORMED BY PALLIATIVIST AND MANAGEDFROM THE ONCOLOGIST

V. Liguori*, F. Amato**, S. Palazzo**Medical Oncology Division,**Palliative Care Division, Cosenza, Italy

Background: To assess the efficacy and safety of technique of day-surgery CVAPDSimplanted for the chemotherapy treatment in cancer patients.

Methods: Ports were implanted via subclavian vein to out-patients of the day-hospitalunder local anaesthesia, by the medical palliativist. Chest radiography was performedafter implanted CVAPDS and all the patients have been under observation by means ofpulsiossimetry and ECG.

Results: 1125 cancer patients received implantable ports between June 2001 and June2006, median age 55 years (range 18-81), 715 female, ECOG 0-2. Diagnostic: 455 pts(40.4%) had colon-rectal cancer, 251pts (22,3%) breast cancer, 155 pts (13,7%) gastriccancer, 53 pts (4,7%) lung cancer, 32 pts (2,8%) oesophagus cancer, 28 pts (2,4%) headand neck cancer and 151 pts (13,4%) other cancers such as ovary, bladder andsarcomas.

Early complications during device insertion (1,5%) included 3 arterial puncture, 3local haematomas, 4 insertion difficulty, 5 malpositions, 1 flexura catheter and 1failure. Late complications related to CVAPDS were 62 device infections (5,51%), witha median follow-up of 213 days: 21 systemic infections, 23 tunnelled catheters, 7venous chest port and 11 venous arm port. Device was removed in 17 occasions .

Conclusions: CVAPDS in cancer out-patients implanted by palliativist and managedfrom the oncologist is safe, efficient and comfortable for the patients. Very few seriouscomplications during the insertion and chemotherapy administration were observed,although there is a negligible number of infections.

For a good quality offered to the patients it is necessary an always greaterinvolvement of the staff to the use of methodical and procedures that of it guaranteeone good management.

D65 SECOND LINE CHEMOTHERAPY WITH ESTRAMUSTINE (E)PLUS DOCETAXEL(D) IN PATIENTS WITH HORMONE-REFRACTORYPROSTATE CANCER (HRPC), RESISTANT TO DOCETAXEL ALONE

Orazio Caffo1, Teodoro Sava2, Evi Comploj3, Romana Segati4, MariannaGiampaolo5, Francesco Valduga1, Alessia Caldara1, Enzo Galligioni1

Medical Oncology Dept of Trento1,Verona2, Feltre4, Anagni5, Urology Dept ofBolzano3

Background: D alone is considered the standard treatment for HRPC. Several studieshave suggested an advantage in associating E to antitubular drugs but its addition toD is not encouraged, due to a potential risk of increased toxicity without clear evidenceof benefit. In the present study we have evaluated if the addition of E to D in patientsprogressed during D alone treatment, may overcome the resistance to D.

Methods: Patients entered in a previous phase II randomized trial with D every 21 days(P ASCO 2006, abs 4625) were offered, after PSA progression, to continue D plus E,at the doses of D 70 mg/m2 IV d1 q3w + E 280 mg/TID PO, starting 1 day prior to D,for 5 consecutive days. The primary end point was the activity of E addition, in terms ofPSA response (e.g. decline ‡50%), according to the consensus guidelines of the PSAWorking Group.

Results: Among the 35 pts progressing to D, 8 refused to continue the treatment orpresented a poor performance status, so the study was restricted to the remaining 27patients. The median age was 68 years and the median PSA value at the time of Eaddition was 78 ng/ml. Before E, pts had received a median of 6 (range 2-14) D alonecourses. Overall, 127 DE courses were administered (median 4, range 1-11), and all but3 were on scheduled time. Major toxicities consisted of grade 4 neutropenia in one caseand a grade 3 constipation in another. In 1 case we observed an ischemic stroke and inanother a deep vein thrombosis, both after only one course. In two other cases thetreatment was interrupted due to peripheral edema. PSA declines ‡ 50% was observedin 15 patients (55.5%); the median time to progression was 18 wks (range 5-67).

Conclusions: It appears from our results than at least half of D-resistant patientsshowed a biochemical response, which suggests a synergistic activity of E-Dcombination. This should be verified in a formal phase III trial.

D66 LOW-DOSE GEMCITABINE AND RADIATION ALTERNATED TOCISPLATIN/5FU IN STAGE IV SQUAMOUS CELL CARCINOMA OFTHE HEAD AND NECK (HN-SCC): A PHASE II TRIAL

Viviana Vigo, Anna Ponzanelli, Almalina Bacigalupo, Michela Marcenaro andMarco BenassoIstituto nazionale per la ricerca sul cancro,




Dow

nloaded from


Background: At the National Institute for Cancer Research of Genoa, Italy, weconducted two consecutive phase II single-institution trials testing the addition ofgemcitabine into an alternating chemo-radiation (CT/RT) regimen that is consideredstandard of care in our Institute for patients (pts) with loco-regional advanced HN-SCC (NEJM, 327:1115,1992). In the former trial (ALT-G trial; 47 pts) high dosegemcitabine was administered with cisplatin and RT (Annals of Oncology, 15:646,2004).

Methods: In the present trial (ALT-g trial) 3 courses of cisplatin, 20 mg/m2/day and5-fluorouracil, 200 mg/m2/day, days 1-5 (weeks 1, 4, 7) alternated to 3 courses ofstandard RT (weeks 2-3, 5-6, 8-9) up to 60 Gy and gemcitabine, 40 mg/m2 on mondayof each week of RT, were administered to 47 pts with stage IV (42 pts) or relapsed aftersurgery (5 pts), unresectable SCC of the oral cavity (11 pts), oropharynx (11 pts)hypopharynx-larynx (24 pts). None had previously received CT or RT.

Results: Seven pts (15%) did not complete the planned treatment. Four of themdied due to pulmonary embolism (2 pts), fulminant pneumonia (1 pt) or uncertaincauses (1 pt). Main grade 3-4 other than local toxicities were: neutropenia (11%),neutropenia with fever (6%), thrombocytopenia (30%), anemia (17% grade 3). 27 ptsreached a CR (57%). 7 PRs were rendered disease-free by surgery mainly on theneck (final CR rate: 72%). At a median follow-up of 37 months, 3-yr results and acutelocal toxicity are compared with those from ALT-G trial and from our data-base of ptstreated with alternating cisplatin/5-FU and RT without gemcitabine (ALT):

Trial pts PFS LRC surv Distant failure gr III-IV mucos

ALT 115 28% 40% 35% 10% 25%ALT-G 47 39% 64% 43% 23% 81%ALT-g 47 43% 54% 50% 6% 37%

Conclusions: In conclusion, the addition of low-dose gemcitabine into a consolidatedcisplatin/5FU and RT alternating program may improve the outcomes with anacceptable increase in acute severe mucositis.

D67 SALVAGE TEMOZOLOMIDE CHEMOTHERAPY, IN PATIENTSWITH HIGH GRADE GLIOMA RELAPSED AFTER POSTOPERATIVERADIOTHERAPY

S. Brugnara, M. Frisinghelli, F. Valduga, O. Caffo, A. Caldara and E. GalligioniOncology Unit S. Chiara Hospital Trento

Background: Until the publication in 2005 of the Stupp regimen, with RT+ concurrentTMZ followed by TMZ for 6 months, the standard postoperative treatment of patientswith high grade glioma, has been long based on adjuvant Radiotherapy. For thesepatients, Temozolomide may represent a valuable option at the time of recurrence andwe report in this study our experience in this setting.

Methods: From 2000 to 2007, a consecutive series of 20 patients relapsed afterpostoperative RT, received in our institution TMZ at a dose of 150 mg/m2 per day ona 5-day schedule every 28 days. If this dose was tolerated, then escalation to 200 mg/m2was allowed.

Results: They were 17 males and 3 females, with median age of 51 years ( range 30-73)and glioblastoma histology in 14 patients, anaplastic astrocytoma in 2 and anaplasticoligodendroglioma in 4. Eighteen pts had received adjuvant RT alone and 2 RT+TMZ.The median time from the end of RT to relapse was 7 months. All patients were treatedwith TMZ at the time of the recurrence. A total of 151 courses were administrated(median 6; range: 3-18 ). The toxicity was mild with only G3 trombocytopenia in 2 pts,requiring subsequent dose reduction. Two pts are not evaluable for response because oflost to follow up (1 pt) or still on treatment (1). Among the remaining 18 pts, 8objective remissions (4CR and 4 PR) and 4 SD were observed (66,6% clinical benefit),while 6 pts progressed. The median TTP was 2 months ( 4 months for OR+SD pts). Atthe median F.U. of 27,5 months, 11 pts are still alive with a median survival of 36,4months.

Conclusions: TMZ appears in our experience, effective and well tolerated in this settingof patients relapsed after postoperative RT.

D68 LOCAL CONTROL IN RADIOTHERAPY TREATMENT OF HEADAND NECK CANCER

E. Tumminello**, L. La Paglia**, G. Evangelista*, F. Sciume*, M. Bono*,P. Montemaggi**U.O. Radioterapia M.Ascoli-ARNAS-Palermo ** Scuola di Specializzazione inRadioterapia- Istituto di Radiologia-Policlinico Universita di Palermo

Aim: To Evaluate the local control in 3D Conformal Radiation Therapy in Head andNeck cancer patients with or without surgery and chemotherapy treatment.

Materials and methods: From January 2000 to October 2001, 98 patients, 47 males and43 females, with head and neck squamous cell carcinomas were treated with radicalradiotherapy in our institution. Definitive diagnosis was obtained through surgeryin all patients (radical surgery or single tumour resection): 23 were of Laryngeal origin,55 arising from Rinopharinx, 12 from the oropharynx and 8 from the hypopharynx.

Sixty one patients underwent bilateral neck dissection ( the removed levelsdepending of stage of tumour visible with imaging techniques as CT and MR ).

All tumours were classified according to the TNM staging system of the UICC (2000).The histological grade was scored according to the WHO system: well differentiated

in 58, moderately differentiated in 26, poorly differentiated in 14. Histological neckstatus was defined by the presence or the absence of tumour in the lymph nodes, 10patients had positive margins, defined as the presence of microscopic level of invasionof the surgical margin of the primary.

All patients received systemic chemotherapy, 42 were treated with adjuvantchemotherapy prior to irradiation, with cis-platinum and 5 fluorouracil, 56 patientsreceived a concomitant chemotherapy with cis-platinum.

Radiotherapy was delivered with radical intent using an immobilization shell.The primary bed tumour and regional lymph nodes were within the field of

irradiation. Treatment was delivered using 2 opposed lateral fields conformed to thelocation and extension of the primary tumour and neck using a Cobalt machines\linearaccelerator with an energy of 15 MeV.

The radiotherapy was administered considering the neck status, type of surgery,presence or absence of positive surgical margins, tumour location.

Patients with tumour of oral cavity and oropharynx received 60 Gy, patients withlaryngeal tumour received 70-75 Gy.

Pts with positive nodes were boosted with electron beams to a total dose of 10 Gyshielding spinal cord after 42 Gy.

The posterior neck was boosted with electrons if 7 Mev, for a total dose of 10 GyThe treatment was administered in 5d\wk for x weeks, specified at the middle plan.When the lower cervical lymph nodes were considered at risk of sub clinical tumour

invasion, a conformed cervico-supraclavicular field was added to the basic technique ofopposed lateral field, the dose to the low neck and supraclavicular nodes was calculatedat 3 cm depth.

Results: All patients were followed by a radiation oncologist, visits were schedules 1month after completion of treatment, then every 3-4 month for the first 2 years aftertherapy, every 6 months for the next 2-3 years. Patients were systematically evaluatedwith clinical assessment and radiobiological imaging. The median follow-up was 36months (range 28-42 ).During the follow-up period 3 patients had a local failure,0 patients a local and regional failure, and 4 patients a regional failure.

Seven patients underwent further intervention:3 received palliative radiotherapy,the others salvage surgery; distant metastases was developed in 0 patients. The presenceof recurrence was influenced by linfonodal involvement an by stage in 20% in T1, 30%in T2 and 45% in T3.

Conclusion: The local control of radiotherapy treatment in Head and Neck canceris related at stage, extension of the tumour size, nodal involvement and histologicaltype of the tumour but, in comparison with a too much radical surgery, she permitsa good local control and, at the same time, a good functional and morphologicalorgan’s preservation.

D69 CNS METASTASIS TREATED BY RADIOSURGERY: FASHIONOR USEFUL?

Luciano Isa3, Alessandro Bertolini1, Fabio Malugani1, Ornella Fusco1, MarioFiumano1, Eliana Berardi1, Elisabetta Menatti1, Virginio Filipazzi2, StefaniaZambelli21Oncology, Ospedale Civile di Sondrio, Sondrio, 2Oncology, Ospedale Sacco,Milano, 3Oncology, Ospedale di Gorgonzola, Milano

Background: Brain metastases are a frequent step of many solid tumors. Whole-brainradiotherapy (WBRT) has been the standard treatment for decades, with modest long-term complications observed using doses no greater than 3 Gy/fraction. Surgicalresection may be beneficial in select populations of patients with single brainmetastases, controlled systemic disease, and good performance status. Radiosurgeryhas demonstrated consistent improvement in local control, with some reports showinga survival benefit with or without WBRT. Combined WBRT and radiosurgery forpatients with two to four brain metastases significantly improves control of braindisease. WBRT alone does not provide lasting and effective care for most patients.

Methods: we evalued clinical outcome of a group of patients treated by radiosurgery(gammaknife), because affected by CNS secondary tumors. This treatment is expensiveand patients went to radiosurgery after clinical and radiological evaluation.

Results: 21 pts (M/F 8/13), median age 64 (range 36-75); PS 0-1; Primary: renal 3,rectal 2, lung 9, breast 5, melanoma 1, mesothelioma 1; median CNS lesion 2 (1-4);median volume of CNS lesions 440 mm3; symptomatic: 12/21; extra CNS lesion 11/21:1 site 5; 2 or more 6; 3/21 had CNS surgery; 7/21 systemic chemotherapy; no adverseevents; WBRT: nobody; retreatment by gamma-knife was required in 3 pts; 6/21deceased because cancer progression; median CNS-progression was 4 months (1-17);median OS was 10 months (range 1.5-29).

Discussion: the role of radiosurgery as a single modality is unclear; however, we can saythat radiosurgery for patients with two to four brain metastases significantly improvescontrol of brain disease.

D70 A ROLE FOR ESTROGENS IN PROSTATE CANCERPROGRESSION

Orazia M. Granata, Letizia Cocciadiferro, Vitale Miceli, Francesco Curto,Lorenzo Marasa, Lucia Polito, Giuseppe CarrubaExperimental Oncology, Clinical Oncology, and Pathology Units, Department ofOncology; Division of Urology; ARNAS-Civico, Palermo, Italy




ownloaded from


Although prostate cancer is a major health issue in westernized countries, beingconsidered a prototypical age-related, androgen-dependent tumor, its molecularpathology remains unresolved. The association between circulating androgens andprostate cancer has been claimed by epidemiologic studies, but resulting data have beeninconsistent and mostly incompatible with the androgen hypothesis. Circulatingsteroid can barely be considered representative of their intraprostatic levels, with theintratissue concentrations being several times (10-1000) greater than respective plasmavalues This is a consequence of expression and/or activity of key steroid enzymes,including 17 b hydroxysteroid dehydrogenase (17 bHSD), 5 a-reductase, 3 a/3 bHSD,sulfotransferase, and aromatase, that may eventually lead to a differential accumulationof derivatives having distinct biological activities. In our studies, cultured humanprostate cancer tissues and cells actively metabolize androgens and estrogens to giverise to more or less biologically active metabolites. In particular, we have observedconsistent aromatase activity in LNCaP cells, leading to local estrogen formation, while17 bHSD exhibited distinct catalytic preferences in LNCaP and PC3 cells. Interestingly,many of the genes encoding for steroid enzymes are highly polymorphic in nature,although data presently available on their relation with prostate cancer areinconclusive. Locally produced or metabolically transformed steroids may differentlyaffect growth of prostate cancer cells. In our studies, estrogen may either stimulate(LNCaP) or decrease (PC3) prostate cancer cell growth, also depending on the receptorstatus. In particular, an imbalance of ER a and ER b expression may be critical todetermine the ultimate estrogen effects on prostate cancer cell growth and, hence, todirect estrogen-dependent tumor progression. Furthermore, accumulating evidenceindicates that estrogens may use an array of both ERE and non-ERE mechanisms,either ligand dependent or independent, to regulate gene transcription. This intricacy isfurther complicated by the presence of receptor isoforms, distinct cofactorinteraction and potential heterodimerization. Future research would use advancedtechnologies and cancer ‘‘omics’’ (genomics, proteomics, metabolomics) to betterdissect estrogen contribution to mechanisms responsible for prostate cancerprogression.

D71 LOW-DOSE THALIDOMIDE (100 MG/DIE) FOLLOWED BYDONOR LYMPHOCYTE INFUSION IN MULTIPLE MYELOMAPATIENTS WITH PROGRESSIVE DISEASE OR RELAPSE AFTER ATANDEM AUTO/ALLOGENEIC STEM CELL TRANSPLANTATION

Massimo Martino, Giuseppe Console, Elisabetta Massara, Giuseppe Messina,Giuseppe Irrera, Caterina Stelitano*, Vincenzo Callea*, Maria Grazia Kropp**,Eugenio Piro**, Maura Brugiatelli, Stefano Molica, Pasquale IacopinoU.O. Ematologia con Trapianto e Terapia Intensiva, *U.O. Ematologia, AziendaOspedaliera ‘‘BMM’’, Reggio Calabria, Italy; **U.O. Ematologia, U.O. OncologiaMedica, Azienda Ospedaliera ‘‘Pugliese-Ciaccio, Catanzaro, Italy; U.O.Ematologia, Azienda Ospedaliera ‘‘Papardo’’, Messina, Italy

The relapse rate after a tandem transplant program with high dose melphalan andautologous stem cell transplant (AutoSCT) followed by a dose-reduced conditioningand allogeneic stem cell transplantation (AlloSCT) in patients with multiple myeloma(MM) is still considerable. Due to a well documented graft versus myeloma effect,adoptive immunotherapy with donor lymphocyte infusion (DLI) has becomea treatment option in patients with relapse after Auto-AlloSCT. To improve theantimyeloma effect of DLI after Auto-AlloSCT in MM, we investigated the effect oflow-dose thalidomide (100 mg) followed by DLI in 9 patients with progressive diseaseor residual disease after the tandem program. The overall response rate was 66.6 % (6/9patients), including 55.5 % (5/9) complete remission (CR) + near CR. Major toxicity ofthalidomide was weakness grade I/II (4/9) and peripheral neuropathy grade I/II (2/9).Only 1 patient experienced mild grade I acute graft versus host disease (aGvHD) of theskin, while no grades II to IV aGvHD and no chronic GvHD was seen. The 2-yearestimated overall and progression-free survival were 100% and 89%, respectively.Adoptive immunotherapy with low-dose thalidomide and DLI induces anantimyeloma effect with very low incidence of graft versus host disease.

D72 OXYCODONE CR IN THE TREATMENT OF CANCER PAIN

M. Scudeletti, G. Berisso,P. Borro, C. Castagneto, I. Grasso, D. Peri, A. Raffo,S. TimitilliOspedale di Sestri Levante ASL 4 chiavarese

Background & Aim: The treatment of pain is one of the most important aspect toguarantee an acceptable quality of life to cancer patients . Oxycodone CR isa semisynthetc opioid analgesic drug classified as a strong opioid approved for thecontrol (management) of moderate to severe cancer pain. The purpose of this studywas to evaluate the efficacy and tolerability of this drug for the relief of moderate tosevere cancer pain in oncological and haemato-oncological patients.

Patients and methods: Sixteen patients affected by different advanced oncologicaldiseases (4 lung, 3 head and neck, 3 breast, 2 pancreas, and 4 colon cancer) and sevenpatients affected by multiple myeloma were evaluated for NRS (average 6,91), for QOL(average 6,80), for the duration of manifested uncontrolled pain (40,11 days) and forthe treatments (65% fentanyl trasdermal, 8,6% tramadol, acetaminophen and fans).

Results: We treated all patients with uncontrolled pain with an average dose of 49,57mg/die oxycodone CR. The following day we improved it to 66,96 mg/die until wereached in a week, a 94,78 mg/die as a treatment dosage. In this way, we obtained a NRS

value of 3,05 with no side effects. In the beginning, 60,86% of patients declared sideeffects, after 3 days 34,78% declared side effects while after seven days only one patienthad nausea and vomit. We evaluated patients for two months, obtaining a final NRS2,24 with 104,71 mg/die oxycodone CR and a very good quality of life.

Discussion: In our oncologic patients, despite the little number of cases cosidered, weconclude that oxycodone CR was effective in controlling moderate to severe cancerpain; moreover it resulted extremely well tolerated within 7 days of treatment. Finally,it was feasible and easy to modify the daily dosage of the drug in relation with the levelof pain.

D73 EAPC GUIDELINES: USE OF OXYCODONE SR

Genni DuseOspedale S. Antonio ULSS 16 Padova

Background&Aim: This study wants to evaluate the efficacy and tolerability ofOxycodone SR in patients with cancer related pain.

Patients and methods: We have analyzed 36 pts with cancer pain: 41,6% hadpneumonia cancer, 22,2% of bladder and prostate cancer, 13,8% had breast cancer,5,5% pancreatic and uterine cancer and 2,7% had ovarian, sarcoma, parotide ormelanoma. Different type of pain was present. Patients had an everage age of 66,81;69,6% are in recurrent disease, 16,6% end of life stage, 13,8 % onset of disease.

KPS status was evaluated at the start of the observation period with a median 85.Pain intensity, calculated using NSR scale, resulted 8,83 in the beginning of the

study. 75 % of patients had received previous pain treatment.Patients started Oxycodone SR therapy at an average starting dose 27,78 mg /day.

Results: Average therapy period: 30,75 days (range 14-60).Average Oxycodone daily dose: 52,78 mg/day (range 20-160).97,22% of patients judged therapy effective.Typical adverse events of opioid class were recorded.

Discussion: Results of this clinical experience show that 95,6 % pts who arrived in ourdepartment reported inadequately treated or not treated severe pain.

The good application in EBM was to follow EAPC guidelines in order to reacha rapid and satisfactory pain control using Oxycodone SR .

This led to decrease NRS score from 8,83 to 3,47, with a very good tolerability. Onlythree patients suspended the treatment for collateral effects (tipical of the class).

Aside from the 2 pts with progressive disease the average dosage was increased to260 mg/day resulting in an excellent pain relief without adverse events for a period of2 months.

D74 FROM CURE TO TAKING CARE

Vittorio D Ferrari*, Marisa Di Fazio, Giuseppe Ricca, Salvatore Grisanti*, FrancescaValcamonico*, Lucia Vassalli*, Giovanni Rangoni*, Patrizia Marpicati*, ElisabettaMontini*, Edda Simoncini*, Giovanni Marini*, *U.O. Oncologia Medica, Azienda Spedali Civili, Brescia [email protected]

The psychological welfare clinical cycle of the cancer patient does not end withdiagnosis and therapy, but also involves rehabilitative and palliative levels, hospicetreatments, home hospitalization. Cancer patients need a tailored therapeuticdiagnostic course and a multidisciplinary team taking care and considering the patientin a comprehensive way because patients need not only welfare, but also psycho-relational support.Methods: 2 years ago we constituted a Unit of Multidimensional Hospital Evaluation(oncologist, business welfare Service, social psychologist, Nurse) UVMD. Once a weekUVMD makes a diagnostic multidimensional assessment of a critical patients; theWelfare assistant meets the patient and then the family to define the choice of strategy.From January to December 2006 they have assessed approximately 180 patients,82 (53%Males, 47% females) of these were considered not eligible for specific therapies(age range between 41 and 79 years), 59 patients were admitted to the Hospice and 23to Home care. In agreement with the General Practitioner at the time of referral tohospital the patient had already defined the attendance model of hospital care: Hospice,attendance at home (such as ADI or other). Objective of the UVMDO model is toensure a timely and appropriate stay in hospital and to restrict hospitalization to thephase of acute symptoms. U.O.Oncologia and Business Social Service assuretherapeutic and psycho-welfare clinical continuity as part of the clinical care model.This project demonstrates (i) the construction of a personalized multi-dimensionalplan through the complementary action between the U.O. Oncologia, Business SocialService and the district, Hospice, A.D.I., non-profit organizations; (ii) how uneasinessand mishandling of the patient while continuing direct care from the hospital to thedistrict can be achieved. All advanced cancer patients died within one or two months ofreferral to UVMDO at home or in hospice.

D75 A PSYCHO-ONCOLOGICAL INTERVENTION: FROM CARE TOTAKE CARE

Dott. I. Ambrosio; Dott. V. Bassolino; Dott. M. Biglietto; Dott. A. M. Grimaldiand G. CartenIDivision of Oncology, AORN ‘‘Cardarelli’’, Naples




Dow

nloaded from


Background: Several studies showed how Psycho-Oncology is a necessary resource toobtain a higher humanization of medical services – especially of Oncology – to givea central position to the patient, respect to his psychological wellness, following a bio-psycho-social prospective.

In occasion of an announcement for the fellowship for psychologists in OncologyDivisions, promoted by FAVO (Italian Federation of the Voluntary Associations inOncology), we elaborated a project for psychological aid during therapy of cancerpatients, in the Division of Oncology of Cardarelli Hospital in Naples.

Objectives: To improve quality of life of the patients, we assumed these objectives:– Keep down cancer related psychological problems;– Improve communication between relatives and caring staff;– Improve compliance of cancer patients;– Sustain cancer patients and their families in critic moments;– Prevent and treat the stress of the operators.

Methods: Clinical activity intend to make use of:– Support interviews to patients and relatives;– Support and self-help groups;– Analysis of the ‘‘Coping’’ styles and use of different strategies to re-define cancerrelated problems;

– Art-therapy laboratories to develop creativity and body expression.

Recipients: Our Psycho-Oncology project is aimed to cancer patients, relatives, friendsand to the sanitary operators of the Division of Oncology of Cardarelli Hospital.

Conclusions: Until today the setting up of a relationship net supported by thedescribed methodology, made easier the communication between operators, patientsand relatives. In fact we noted a gradual reduction of problematics/conflictualities ofcancer patients in range of their disease as well as operators stress.

D76 ROLE OF NUTRITIONAL COUNSELING FOR DIETARYSUPPORT TO CANCER PATIENTS

L. Rovera, E. Parente*, R. Bianco, P. D’Elia, D. Vassallo, G. GalatolaNutriotion Unit- Gastroentorology, Institute for Cancer Research andTrattament- Candiolo- Italy. *Counselour S.I.Co

Dietary counselling is essential for an effective improvement of both the nutritionalstate and the prognosis in patients with chronic illnesses. This should consist inachieving a therapeutic agreement between the health carer and the patient, wherebythe former sustain and motivate the latter, who remain protagonist of his/her own lifebut is made aware of the reasons for the necessity to face dietary changes. Project. Asfrom May 2005 we have introduced the added presence of a professional advisor tomonitor and learn the communication modalities employed during nutritionalconsultations at our Institution. During this learning phase we have been able tohighlight some critical factors affecting both the modalities of communicating dietaryinformation to the patient and the need for changing their nutritional habits. We havethen used this phase to construct a more adequate and effective communicationpathway. The aim was to create a comfortable ‘‘therapeutic climate’’ for the patient,where needs, expectations, emotions and doubts can be more freely expressedregarding the required changes. We have reviewed the process of the nutritionalconsultation with respect to: a) reception and acknowledgment of the patient asa person; b) nutritional history and shared assessment of the amount of food intake;c) justification and explanation of the physical examination and anthropometricmeasurements; d) gradual transmission of information; e) shared construction of anagreed dietary pattern; f) verification of the effectiveness of information transmitted tothe patient and to the accompanying persons; g) weekly or twice weekly nutritionalmonitoring during the initial treatment phase to assess the achievement of the dietarychange.Conclusions: The project of using dietary counselling to build an effective nutritionalpathways, in which the patient remain an active subject and is not just a passive receiverof treatment orders, facilitates the relationship between care giver and patient andfavours the achievement of the necessary dietary changes.

D77 TREATMENT OF PENIS CARCINOMA: REPORT OF 19 CASES

Michele Aieta1, Franco Morelli1, Vanna Maria Valori1, Stefania Ronga1, DomenicoDi Noia2, Nicola Sebastio2, Elena Ricci Barbini2, Vittorino Ricci Barbini 2 andEvaristo Maiello1

1Oncology Unit 2Urology Unit -IRCCS ‘‘Casa Sollievo della Sofferenza’’ SanGiovanni Rotondo

Introduction: Penile cancer, while is relatively rare in the western world, remainsa disease with severe morbidity, not to mention significant psychological ramifications.Of all penile cancers, 30% are diagnosed with advanced disease.

Matherials and methods: Between 1996 and 2006 at our Institution, 19 patients (pts)had undergone a partial penectomy for T1-2 squamous cell carcinoma of the penis. Allpts initially presented with bilateral impalpable lymphnodes.

Results: Median age was 66 years (range 46-78). Seven pts experienced a local diseaserecurrence after a median time of 6 months (range 4-8) and underwent to totalpenectomy. Considering other types of events, 7 pts developed lymphnodes metastases

and underwent to a lymphadenectomy of the ipsilateral groin, 3 pts had distantmetastases and were treated with chemotherapy (cisplatin and infusional 5-FU). At themedian follow up of 67 months (range 14-126), 12 of 19 pts (63%) were disease freeand alive. Median survival time was 18 months (range: 7-60).

Conclusions: No standard therapeutic guidelines as to the best treatment strategyaccording to different stages, including efficacy of conservative non surgical modalitiesand indications for lymph nodal dissections, are available so far. Improvements insurvival and quality of life likely require the incorporation of multiple modalities intothe treatment of advanced penile carcinoma.

D78 LONG TERM QUALITY OF LIFE AND PSYCHOLOGICALRESPONSE AFTER SURGERY AND RADIOTHERAPY IN HEAD ANDNECK CANCER PATIENTS

Massimiliano Garzaro, Paola Caldera, Giancarlo Pecorari, Laura Amodeo,Antonella Varetto, Mario Airoldi, Riccardo TortaOtolaryngological Clinic II, Psycho-oncology Unit - University of Turin

Aim: This study was aimed to assess, in head and neck cancer survivors, treatmentimpact on quality of life and psychological functioning, particularly after facialdisfigurement determined by surgery and radiotherapy.

Methods: Thirty-two surgery and radiotherapy cancer patients were enrolled. Allpatients underwent to major otorhinolaryngoiatric surgery, with pedicle or free flapreconstruction and adjuvant radiotherapy. Patients were submitted to a broad testbattery 12 month after the end of radiotherapy, during a follow upotorhinolaryngoiatric visit.

Long-term outcome on quality of life (QOL) was assessed by EORTC QLQ C30,including the Head and Neck Cancer module (H&N35). Psychological symptoms wereevaluated by MADRS, HADS, HAM-A to rate depression and anxiety; MINI-MAC toassess the psychological adjustment to cancer; Karnofsky Performance status todetermine patients functional impairment. Severity and characteristic of pain, whenpresent, were assessed by a visual analogue (VAS) and QUID. Personality profiles ofpatients was investigated by TCI, to evaluate if specific personality traits could beassociated to higher risk of poor quality of life and depression in cancer survivors.

Results: In our sample, low levels of anxiety and depression were observed (HADS-Amean 5; HADS-D mean 4,5; MADRS mean 7,2; HAM-A mean 9,8), associated withhigh performance status (KPS mean 89%). MINI-MAC scores suggested that patientswere able to adopt functional and adaptive coping styles, with higher fighting spirit(mean 3,1), fatalism (mean 2,8) and negation (mean 2,8). Patients reported high levelsof quality of life (EORTC global QoL mean 75,7) and perceived health status (EORTCglobal health mean 76,4). Peculiar personality profiles were observed, probably relatedto pre-morbid conditions and illness experiences.

Discussion: Our preliminary data suggest that head and neck cancer patients do notnecessarily experience poor quality of life and depression, during 12-month follow-upperiod. However, caution is recommended: in this peculiar population, theseencouraging findings could partially reflect low illness insight.

D79 NON-INFERIORITY TRIALS: ARE THEY USEFUL FORIMPROVING QUALITY OF CARE IN CANCER? A SURVEY FROM THEITALIAN OSSC

Elena Albertazzi2, Irene Floriani1, Nicole Rotmensz2, Filippo de Braud2, ValterTorri11Istituto Mario Negri, Milano Istituto; 2Istituto Europeo di Oncologia, Milano

Non-inferiority trials are intended to show that the effect of a new treatment is notworse than that of an active control by more than a specified margin. These trials havea number of inherent methodological weaknesses that superiority trials do not, andrigid criteria for assessing scientific and clinical relevance are needed, particularly incancer, were new high costly drugs, with different toxicity profiles are emerging. In thissituation the capability of trials of clearly assessing the cost/benefit profile ofcomparison under investigation is often critical. This project is aimed at assessingthe prevalence, as well as specific methodological, statistical and clinical aspects ofnon-inferiority trial protocols. We assess protocols available in the OsSC database,relative to oncological studies submitted to Italian ECs from January 2000 to December2006 and positively evaluated by the Ethical Committee of coordinating centre. Werestrict the evaluation to protocols of randomised studies on antitumoral drugs, witha time to event endpoint. Details on type of sponsor, primary endpoint, presence ofrisk-benefit ratio assessment, reference and experimental arms, criteria for definingnon-inferiority are collected.

Among the 1043 (85%) evaluated protocols out of 1229 available, 23 non-inferioritytrials have been identified, 3 of phase II and 20 of phase III. Only in 4 cases (17%),the study was a non-for-profit research. The presence of a non-for-profit sponsor innon-inferiority cancer trials is much lower than the overall figure (46%), reported by2006 Bulletin of Clinical Trials of Drugs in Italy. While the justification of the controlarm is well defined, the same is not true for the choice of the margin for definingnon-inferiority and for the definition of the risk-benefit ratio. Since a trend towardstesting non-inferiority at earlier experimental phase has been noticed, it seemsimportant to monitor this tendency, due to its obvious implications.




ownloaded from


D80 DOWNREGULATION OF THE CASC2A GENE IN ENDOMETRIALCANCER

Paola Baldinu, Antonio Cossu*, Antonella Manca, Maria P. Satta, Maria C. Sini,Grazia Palomba, Milena Casula, Mario Budroni*, Francesco Tanda*, GiuseppePalmieriIstituto di Chimica Biomolecolare-CNR di Sassari; *Azienda USL1 di Sassari

Background: Chromosome 10q25-q26 has been strongly correlated to endometrialtumourigenesis. We previously identified a novel human gene, CASC2, at chromosome10q26. One out of the three alternative transcripted forms, CASC2a, has beendemonstrated to be mutated at a low frequency in endometrial cancer (EC). In thisstudy, role of the CASC2a gene in cancer has been further defined.

Methods: Tumour and corresponding normal tissues were analysed for CASC2amRNA expression by real-time RT-PCR and mutation status by PCR-basedapproaches.

Results: A significantly decreased level of CASC2a transcripts was observed in 13/17(76%) EC tissues as well as in 6/9 (67%) colorectal cancers. Exogeneous expression ofCASC2a in undifferentiated AN3CA endometrial cancer cells inhibited cellular growthin anchorage-independent growth assays. Finally, infrequent CASC2a mutations areable to impair the gene function.

Conclusions: Altogether, our findings strongly suggest that CASC2a may act asa tumour suppressor gene, with both epigenetic and genetic alterations concurring togene inactivation. Down-regulation of CASC2a may provide a growth advantage in ECcells.

D81 THE ROLE OF DOXORUBICIN AND EPIRUBICIN FOR THETREATMENT OF PATIENTS WITH METASTATIC HORMONE-REFRACTORY PROSTATE CANCER

Roberto Petrioli1, Alessandra Pascucci1, Edoardo Francini1, Anna Ida Fiaschi2,Angela Sciandivasci1, Salvatora Miano1, Stefania Marsili1, Guido Francini1

Department of Human Pathology and Oncology1, Department ofPharmacology2

Doxorubicin (Dox), or adriamycin and its analogue epirubicin (Epi), alone or incombination with other agents, have been extensively used in the treatment ofhormone-refractory prostate cancer (HRPC), but controversial results have beenreported and their role in this disease remains unclear. The aim of this review was todiscuss the efficacy and toxicity of Dox and Epi for the first-line treatment of patientswith HRPC. Our analysis, performed on all main clinical studies published as formalpapers in peer-reviewed journals, suggests that Dox and Epi are effective as a singleagent and in combination chemotherapy regimens for the treatment of HRPC. Withthe limitation in the analyses of older studies, the use of anthracyclines alone showed anOR from 0% to 55%, and a PSA response from 10.7% to 81.0%, an encouragingimprovement in bone pain ranging from 14% to 87%, and similar activity of the weeklyover three weekly administration of both Dox and Epi. Dox or Epi combined withother agents suggested an OR ranging between 0% and 75%, and a biochemicalresponse between 0% and 68.4%, with an overall greater proportions of PSA declines(>50%) than anthracyclines alone. The better results, also in terms of palliation andoverall survival, were obtained when anthracyclines were combined with estramustinephosphate, ketoconazole and vinblastine (KAVE regimen), or with dose-escalatingcyclophosphamide, or with docetaxel. The spectrum of toxicity associated with Epi wasqualitatively identical to that caused by Dox in the treatment of metastatic HRPC.Congestive heart failure was rarely observed with weekly anthracyclines alone, probablybecause this schedule is less cardiotoxic than 3-weekly administrations. Given thatHRPC includes a heterogeneous group of patients with variable rates of tumor growth,the combination of anthracyclines with docetaxel (today approved for the treatment ofHRPC) maybe in an intermittent strategy, might be interesting in terms of palliationand biochemical response, as suggested by preliminary findings.

D82 TEMOZOLOMIDE AND RADIOTHERAPY IN HIGH-GRADEMALIGNANT GLIOMA: PRELIMINARY RESULTS

Zaira Coccorullo1, Massimiliano Boccardo2, Riccardo Ratti1, Domenico Guarneri1,Gianfranco Addamo1, Giuseppe Colloca1, Antonella Venturino1 and ElisabettaCampora1

1Division of Medical Oncology – Ospedale Civile ‘‘G. Borea’’, Sanremo, Italy2Department of Neurosurgery – Azienda Ospedaliera Santa Corona, PietraLigure, Italy

Background: Median survival for malignant gliomas even with aggressive surgery,radiation and chemotherapy is less than 1 year. Temozolomide, an oralimidazotetrazine second-generation alkylating agent that enters the cerebrospinal fluidhas demonstrated antitumor activity in high-grade glioma.

Aim: To evaluate the safety profile and the overall survival of patients (pts) treated withtemozolomide (TMZ) in combination with radiotherapy (RT) in high-grade cerebralglioma.

Methods: RT to limited fields was administered once a day at 2 Gy/fraction, 5 daysa week for 6 weeks, for a total of 60 Gy, was administered with concomitant TMZ 75

mg/m2 daily for 7 days a week followed by 6 cycles of TMZ 150-200 mg/m2 daily ondays 1 to 5 every 28 days.

Results: Since November 2004, 10 pts median age 57 years (range 34-69), 7 males, 3female all with ECOG PS = 0. Pathology was as follows: anaplastic astrocytoma in 3cases, glioblastoma in 5 case, astrocytoma low grade 1 case, in one case glioma grade II.Four patients underwent non-radical surgical tumor resection, 4 underwent R0resection and two were considered inoperable. All pts completed RT concomitant withTMZ as planned and five also the following CT. One pts didn’t receive TMZ and fourpts only three cycles due to progression disease. Toxicity G3-G4 was not reported.

At a median follow-up of 336 days (range 172-784) 6 patients died of progressivedisease and 4 patients are alive; median PFS was 230 days. Five pts underwent secondline CT with PVC schedule.

Conclusions: Concomitant TMZ and RT followed by 6 courses of TMZ is a safe andfeasible schedule, active in high-grade glioma.

D83 LOCALLY ADVANCED HEAD AND NECK (H&N) CANCER:COMBINED RADIO-CHEMOTHERAPEUTIC TREATMENT: RESULTS,TOXICITY AND PERFORMANCE STATUS (PS)

E. Burattini; G. Coiro; M. V. Zoffoli; F. Todi; F. Satta; I. Pavese; F. Bianciardi;*A. M. Di Palma; *; U De Paula*; G. Capuano1 and M. Di PalmaSan Pietro Fatebenefratelli Hospital-Rome-Oncology, Radiotherapy* andSurgery1 Departments

H&N tumours are squamous cell carcinomas and represent at least 3% of all the newdiagnosed cancer per year. The combined modality treatment with radiation therapy(RT) and continuous infusion chemotherapy (CT) is highly effective. Since March2005 to March 2007, 38 patients (pts), with locally advanced H&N squamous cellcarcinoma, poorly differentiated (G2-G3), were enrolled. All pts (31 male, 7 female)had a PS= 0-2 (ECOG): PS0: 9 pts; PS1: 22 pts;PS2: 7 pts. The median age was 60years (range 40-77).Combined treatment consisted of non-conventional RT: 120 cGytwice day for 5 consecutive days, for 6 weeks, associated with continuous infusion CTwith Cisplatin :5 mg/mq/die for 5 consecutive days and 5-Fluorouracil: 200mg/mq/diefor 5 consecutive days. Both drugs were infused through a central venous access(Port-A-Cath).Results: Response Rates (RR) were as follow: 9 Complete Responses (CR),18 PartialResponses (PR), 8 Stable Disease (SD), 3 Progressive Disease (P). On the whole weobtained 71% RR (27/38 pts), 21% SD (8/38 pts) and 0,7% P (3/38 pts).

Toxicity: The main toxicities were: mucositis (G3-4) in 84% of pts (32/38), fatigue(G3) in 50% (19/38), leukopenia (G2) in 31% (12/38), anemia (G2) in 44% (17/38)and nausea (G1) in 47% of pts (18/38). 17 pts (44%) discontinued CT, for severemucositis, continuing RT, for 1 week, and underwent parenteral or enteral nutritionuntil toxicity recovery. Weigth loss was observed in 72% of pts.

Performance status: 44% (4/9) of pts with baseline PS0, reached PS1; 59% (13/22) ofpts with baseline PS1, reached PS2; 71%(5/7) of pts with baseline PS2, reached PS3.

In conclusion: Radio-chemotherapeutic approach is effective in locally advanced H&Ncancer, but his potential severe toxicity requires an accurate selection of pts, realizingan integrative nutritional therapy before starting combined treatment anda substitutive nutritional therapy during and immediately after.

D84 COMBINATION OF TRANSDERMAL FENTANYL ANDMORPHINE IN PATIENTS WITH ONCOLOGICAL PAIN RESISTANT TOFENTANYL ALONE: 5 PATIENTS’ REPORT

S Piazza, A Prino, G Delzanno, V Rossi, L Forti, S Poletti, O AlabisoA.O. Maggiore della Carita – NOVARA

Background: Recents evidences suggests that fentanyl and morphine have synergiceffect in pain control.

Methods: Combination of two drugs has been used in oncologic patients with painresistant to transdermal fentanyl alone.

Patients were treated with transdermal fentanyl at doses from 25 to 100 microgramsfor hour; escalation of dose wasn’t effective or not well tolerated.

One patient were shifted from fentanyl 100 micrograms for hour to subcutaneousmorphine 80 mg in 24 hours infusion, obtaining reduction of pain; adding transdermalfentanyl 25 micrograms for hour we obtained complete pain control.

One patient, treated with trandermal fentanyl 75 micrograms for hour was shifted totransdermal fentanyl 50 micrograms for hour in combination with morphinesubsatained release 60 mg in 24 hours in two administrations, obtaining complete paincontrol.

Other 3 patients were treated with transdermal fentanyl at doses from 25 to75 micrograms for hour; we added morphine at dose from 15 to 45 mg in 24 hours(divided in 3 administrations), obtaining pain control.

Conclusions: we observed that combination therapy has been, in those five patients,more effective than single drug therapy to obtain complete pain control, withoutsignificant escalation dose. We didn’t observe significative side effect, and thecombination treatment has been well tolerated. Pain control were more difficult atworsening of performance status.




Dow

nloaded from


D85 FOTEMUSTINE ASSOCIATED WITH BEVACIZUMAB INPRETREATED STAGE IV MELANOMA PATIENTS: RESULTS OF ASPONTANEOUS STUDY

Meucci I1, Fioretto L2, Zuppiroli A3, Pimpinelli N 1,4.1 D.H. Oncologico, P.O. Firenze Centro, 2 U.O. Oncologia Medica, P.O. S.M.Annunziata, 3 U.O. Cardiologia, P.O. S.M.Annunziata, Azienda Sanitaria diFirenze, D.H. Presidio Osp. Firenze Centro; 4 Dip. Scienze Dermatologiche,Universita degli Studi di Firenze

Improving response rate (RR) and overall survival (OS) are primary goals in stage IVmelanoma patients. To date, no treatment proved superior to monochemotherapy interms of OS, although different biochemotherapy regimens were able to improve RRand progression-free survival (PFS). Among targeted therapies, bevacizumab – an anti-vascular endothelial growth factor humanized monoclonal antibody – proved higlyeffective in metastatic colonic cancer and, more recently, showed encouraging resultsin other solid tumors, including melanoma. The aim of our spontaneous, pilot studywas to assess the efficacy (response rate, RR; progression-free and overall survival, PFSand OS) and tolerability (clinical and haematochemical) of a combination offotemustine and bevacizumab in pretreated stage IV melanoma patients. We havetreated 8 patients (6 M, 2 F; median age 56.5; 3 stage M1a, 2 M1b, 3 M1c) with thefollowing regimen: fotemustine 100 mg/sm i.v. days 1,8,15 (induction); 4 weeks rest;then once every 21 days for 6 cycles (maintenance), associated with bevacizumab(5 mg/kg) i.v.. We observed a partial response in 2/8 patients (25%), stable disease in5/8 (62%) and progression in 1 patient, with a median PFS of 8.5 months and OS of11.5 months. Interestingly, we also observed a good objective response in the three M1cpatients (two with extensive liver metastases, and one with extensive cardiacmetastases). The toxicity profile was overall very good (grade III-IV thrombocytopeniain 2/8 patients, mucocutaneous haemorragia in 1/8 patients). The encouraging resultsof this and other spontaneous studies suggested the need of a multicenter, phase II trial,currently ongoing under the lead of the Istituto Nazionale Tumori di Milano, 2nd

Medical Oncology unit.

D86 LOW-DOSE INTERFERON ALFA AND INTERLEUKIN-2 IN THETREATMENT OF STAGE IV MELANOMA PATIENTS IN REMISSION ORSTABLE DISEASE AFTER FIRST LINE CHEMOTHERAPY: RESULTSOF A SPONTANEOUS STUDY IN A SMALL SERIES OF PATIENTS

Pimpinelli N1,3, Meucci I1, Fioretto L2

1D.H. Oncologico P.O. Firenze Centro e 2U.O. Oncologia Medica, P.O. S.M.Annunziata, Dipartimento Oncologico, Azienda Sanitaria di Firenze; 3Dip.Scienze Dermatologiche, Universita degli Studi di Firenze

In stage IV melanoma patients, improving response rate and overall survival areprimary goals. In addition, consolidation of remission or stable disease whilemaintaining an acceptable quality of life is certainly an important issue and a difficultchallenge. In this regard, the combination of low-dose interleukin-2 (IL2) andgranulocyte-macrophage colony stimulating factor proved effective in previous studies.The aim of our spontaneous, pilot study was to assess the tolerability (clinical andhaematochemical) and efficacy (time-to-progression, TTP) of a combination of low-dose alfa-3 recombinant interferon (aIFN) and IL2 in stage IV melanoma patients inremission or stable disease after first line chemotherapy. We have treated 6 patients(5 M, 1 F; median age 54; 1 stage M1a, 4 M1b, 1 M1c) according to the followingregimen: aIFN 600,000 IU (antiangiogenetic effect, MHC upregulation) s.c. days 1-6and IL2 3,000,000 IU (> number and activation T cells) days 8-13), recycle every 21days, for 6 cycles. All patients showed an excellent tolerability (mild flu-like syndromein 5/6 patients; mild, generalized urticarial reaction in 2/6; mild astenia in 4/6 patients;no documentable haematologic or organ toxicity). In 4/6 patients (66%), remission orstability were maintained for 6 months or more, with median TTP 7.5 months. Theresults of this preliminary, monocenter study are encouraging, although they clearlyindicate the need of a multicenter, phase II trial, possibly associated with translationalresearch (e.g., evaluation of regulatory T-cells, Treg), in order to assess the possibleclinical efficacy of this combination treatment with the overall most used and effectivebiologic response modifiers.

D87 IMPROVEMENT OF SURVIVAL OF MALIGNANT LYMPHOMASIN RECENT YEARS; A POPULATION BASED STUDY FROM THEMODENA CANCER REGISTRY

Stefano Luminari, Manulea Proietto, Marina Cesaretti, Ivan Rashid, Monica Bellei,,Luigi Marcheselli, Alessia Bari, and Massimo FedericoDipartimento di Oncologia ed Ematologia, Cattedra di Oncologia II, Universita diModena e Reggio Emilia, Modena

We evaluated the survival of 1,582 cases of Malignant Lymphomas diagnosed in theprovince of Modena between 1997 and 2003 and recoded according to the WHOclassification, with the aim of assessing most recent trends in survival for these cancers.Relative survival (RSR) was considered as principal study endpoint; period analysis wasused for estimating longer survival data for patients with a relative short medianfollow-up. After a median follow-up for living patients of 54 months (range 2 to 118),741 had died and 841 remained alive, including 21 cases lost at follow up. Lymphoma

progression was found to be the most frequent cause of death In our studypopulation,(70.1% of deaths). The 1, 3, and 5-year RSRs for all lymphoma cases were81%, 73%, and 70%, respectively. Interestingly the impact of the diagnosis on lifeexpectancy for some lymphoma subtypes, including HCL and MF/SS, was null orminimal as evidenced by 5-year RSR of 100% and 97%, respectively. An overallimprovement in RSR was observed over time with a 5-year RSR rising from 66%to 74% for cases diagnosed during 1997-2001 and 2002-2003 respectively (P=0.034).A statistically significant improvement in the 5-year RSR for 2002-2003 patients wasestimated for patients with DLBCL (from 41% to 54%; p=0.015), Hodgkin Lymphoma(from 82% to 96%; P=0.004), and for T-NHL (from 73% to 87%; P<0.001). Survivalimprovement for T-NHL was observed only for Mycosis Fungoides and not for otherPeripheral T-Cell Lymphomas. A trend toward an improvement in RSR was alsoobserved for Indolent B-cell NHL including Follicular Lymphomas. Our data confirmthat there has been an overall improvement in outcome of Malignant Lymphoma whencompared with available historical controls for the major European countries.Moreover our study reflect major recent advances in the curability of some lymphomasubtypes that could be explained by the use of more effective drugs, such as monoclonalantibodies, by a better use of existing drugs, and by the use of more accurate diagnosticand/or prognostic tools.

D88 DENTAL CARE AND TOOTH EXTRACTION AS A RISK FACTORFOR DEVELOPING OSTEONECROSIS OF THE JAW AFTER LONGTERM BISPHOSPHONATE THERAPY IN PATIENTS WITH BONEMETASTATIC CANCER

Vincenzo Pitini, Claudia Naro, Carmela Arrigo, Barbara Buemi, Anna Bene,Giovanni Picone, Giuseppe Lupo, Giuseppe AltavillaHuman Pathology Dpt, Medical Oncology and Innovative Therapies Unit,University of Messina

Background: Association between osteonecrosis of the jaw (ONJ) and bisphosphonatetreatment in patients (pts.)with Multiple Myeloma, breast cancer and prostate cancerhas been increasingly reported in the literature. Risk factor for this complicationinclude presence of infection, recent dental extraction and any oral surgical procedurewith bone exposure.

Methods: This is a retrospective review of our experience with patients diagnosed withbone metastasis who developed ONJ while treated with bisphosphonates, betweenJanuary 2002 and December 2006. Presentation, age, dental status, and outcome werereviewed. Logistic Regression was used to test for statistical significance.

Results: 100 pts. with bone metastasis secondary to breast cancer(40pts),multiplemyeloma(50pts),prostate cancer(10pts), median age 63 years, treated withbisphosphonates were reviewed. ONJ developed in 5 (5%) pts. Age did not impactoccurrence of ONJ. All 5 patients developed ONJ after a minimum of 100mg ofZoledronic Acid and 2700mg of Pamidronate. All pts. had a history of previous toothextraction and inadequate dental care. Three pts. were treated with debridement andantibiotics and their lesions healed. Two pts. ended up suffering from a chronicallyexposed bone.

Conclusion: ONJ is a serious complication of bisphosphonate therapy and it affecteda significant proportion of our patients. Our data suggests a strong association betweendental care, tooth extraction, and the development of ONJ.

D89 FOTEMUSTINE (FM) IN PRETREATED METASTATICMELANOMA (MM) PATIENTS

M. Frisinghelli, S. Brugnara, M. G. Tomasi*, F. Valduga, O. Caffo, A. Caldara,E. GalligioniMedical Oncology and Dermatology* Units - S.Chiara Hospital, Trento

Background: FM is a chloronitrosourea which has shown a greater than 20% response-rate in a large phase II trial, in patients with MM.

Methods: From June 2003 to April 2007, mostly pretreated patients with advancedmalignant melanoma, non amenable of surgery, received in our institution FM 100 mg/sqm i.v weekly for 3 weeks. Nonprogressive pts received a maintenance treatment withFM 100 mg/sqm every 3 weeks, to disease progression or severe toxicity.

Results: Among the 12 patients of this series, median age was 57,5 years (34-76), PS was0, 1 and 2 in 42%, 25% and 33% respectively. Nine pts had 2 or more metastatic sitesand 9 (75%) had received at least 1 prior regimen for MM.

The median number of administered doses was 3 (1-9), because half of the pts havereceived only the first 3 weekly doses, due to the severe and persistent toxicity.

Toxicity, evaluable in all pts, consisted of prolonged G3/G4 thrombocytopenia in6 pts, G4 neutropenia in 2, G3 liver toxicity in 1 and G3 nausea/vomiting in 2 pts.

Four out of 12 pts are not evaluable for response: 1 because early death, 2 lost atfollow up and 1 still on treatment. Among the remaining patients, 3 partial responses,2 stable disease and 3 progressive disease were observed. The median TTP was 4months (with 4,10 and 14 months for responding pts)

Conclusion: It appears from our experience that second-third line FM treatmentmay provide a clinical benefit to some pretreated MM patients. However the toxicity ofFM in this setting, requires a careful patient selection, reserving this therapy to patientsin acceptable conditions and who strongly require further treatment.




ownloaded from


D90 WEEKLY DOCETAXEL FOR ADVANCED HORMONE-REFRACTORY PROSTATE CANCER-HRPC

A. Pepe, A. Usset, C. Calabria, G. Savio, V. Palmisano, V. Leonardi, A. Laudani,C. Arcuri, B. AgostaraDipartimento Oncologia, Divisione Oncologia Medica, P.O. ‘‘M.Ascoli’’ ARNASCivico, Palermo

It has been shown that mitoxantrone-based chemotherapy plus prednisone palliatespain and improves the quality of life (QoL) but not the overall survival (OS) in menwith advanced HRPC.

Data from a randomized trial (TAX 327) show a significant improvement in OS forpatients treated with 3-weekly docetaxel plus prednisone (D3w+:P) in comparison topatients treated with mitoxantrone plus prednisone (M+P); no significative differencein OS has been found between patients treated with weekly docetaxel (Dw)+P andpatients in treatment with M+P. QoL has been improved in both arms of D comparedwith M arm, hematological toxicity was worse in D3w arm, non hematological toxicitywere similar in both arms of D. We describe our experience with Dw+P in men withHRPC.Methods: 24 men with metastatic HRPC received P 5 mg twice daily and D 30 mg/mqintravenously weekly for 6 consecutive weeks, followed by 1-week rest period.Treatment was continued for 3 months or until disease progression or unaccettabletoxicity. Biochemical response was defined as a 50% reduction of PSA levels. Theprimary end-point was progression free survival (PFS), objective response rates (ORR)and QoL.

Results: After a median follow-up time of 30 months, a biochemical response wasobserved in 14 pts (58,3%) and the median PFS was 5,8 months. ORR were observed in37,5% of patients (9 pts) with bidimensionally measurable disease. Grade 3neutropenia, nausea and vomiting were manageable. 16 patients (66,7%) had pain-reduction with improvement in QoL.

Conclusion: Our experience showed that treatment with Dw+P allows to gainresponses in terms of ORR, serum PSA level, pain, QoL and tolerability: this regimenshould be further investigated in HRPC.

D91 RETROSPECTIVE ANALYSIS OF CONCOMITANT TREATMENTWITH 3-DIMENSIONAL CONFORMAL RADIOTHERAPY ANDTEMOZOLOMIDE IN HIGH-GRADE GLIOMA PATIENTS

L. Landi1, A. Fontana1, C. Galli1, L. Galli1, L. Benvenuti2 , R. Gagliardi2,S. Campoccia3, M. Bosio3 and A. Falcone1,4

1U.O. Oncologia Medica, Azienda USL-6, Livorno, Istituto Toscano Tumori, Italy

Background: We retrospectively reviewed a high-grade glioma database at the Neuro-Surgery Department, Radiotherapy and Medical Oncology Departments of LivornoCivil Hospital, consisting of 15 consecutive patients (pts) treated at our institutionsfrom July 2005 to December 2006.

Patients and methods: 11/15 pts (73 %) had GBM, 3/15 pts (20 %) had AOA and 1 pt(6 %) had mixed histology. Median age was 61 years (39-72 range), M/F 9/6. Nine outof 15 pts (60%) received subtotal surgical resection, while 6 received only biopsy.Twelve pts (80%) undergone concomitant treatment with 3-dimensional conformalradiotherapy (3DCRT) (60 Gy) plus temozolomide (TMZ) at the dose of 75 mg/sqmorally daily during RT, followed by six cycles adjuvant (or maintenance) TMZ at thedose 200 mg/sqm orally days 1-5 every 28.

Results: Two pts (13%) experienced one episode of G3 neutropenia and G4thrombocytopenia recovered without sequaele, one had Pneumocystis Cariniipneumonia and one case of deep venous thrombosis recovered respectively withantibiotic therapy and anticoagulant therapy. Nor febrile neutropenia neither toxicdeaths have occurred. Nine pts (60%) were assessed for response: two pts ( 22%) hadcomplete response, one (6%) had partial response and four (44%) had stable disease,while 5 (33 %) progressed.

Conclusion: Our data demonstreted that treatment with 3DCRT plus TMZ is safe andshowed an interesting activity according to literature findings.

D92 A PROJECT FOR SHORT HOSPITAL STAY AFTER SURGERY

R. Bianco1, P. Torrisi2, A. Madau2, A. Muratore2, L. Rovera1, F. De Bernardi1,L. Capussotti21Nutrition Unit, Gastroenterology Unit, 2Department of Surgery, AntalgicTherapy and Palliative Care, Institute for Cancer Research and Treatment,Candiolo, Italy

Background: Preoperative patient information improves post-operative recovery,compliance to treatment and shortens in-hospital stay. AIM. To assess feasibility andefficacy of a project for shortening hospital stay following surgery in cancer patients.

Methods: The project includes a) specific analgesia protocols; b) early re-feeding andmobilisation protocols; c) pre-admission patient interview in order to improve healthcare and compliance to a treatment schedule entailing: 1) explanation of the surgicaloperation by the surgeon; 2) screening for assessing malnutrition risk using the

Subjective Global Assessment, SGA; 3) information on the modalities for early post-operative mobilisation; 4) Encouragement to initiate oral food intake and oralnutritional supplements on the first day after of surgery. Specific and accurate inclusionand exclusion criteria have been used to select patients undergoing colorectal or liversurgery eligible to participate to the project.

Results: From August 2006 to April 2007, 77 patients were operated on forcolorectal cancer or liver metastases: 35 (45.5%) were included in the short stay surgeryprotocol. Median age was 63.5 years in the short stay group (A) versus 68.5 in thecontrol group (B) (p=0.5). Overall median hospital stay after surgery was 7 days: 6 daysin the group A and 7.5 days in the group B (p=0.01). twenty-two (62.9%) of the35 group A patients completed the short stay surgery protocol. The median hospitalstay was 5 days in the group A patients who completed the protocol versus 7 days in thegroup A patients who did not (p=0.001). The cause of non-adhesion to the protocolwas intestinal obstruction at the 3rd postoperative day. None of the group A patientsrequired a new hospital admission due to the early discharge. The median hospital stayof the patients who had colorectal surgery in 2005 was 7.8 days and was significantlylonger that the median hospital stay of group A patients (p<0.001).

D93 ARTIFICIAL DIETARY INTEGRATION IN CANCER PATIENTS:PRELIMINARY ASSESSMENT IN LONG TERM TREATMENT OFPATIENTS

D. Vassallo2, R. Bianco1, P. D’Elia2, M. Roma2, C. Ortega2, L. Rovera1

1Nutrition Unit, Gastroenterology Unit, 2Univ. Div. Med. Onc. and Hemat.,Institute for Cancer Research and Treatment, Candiolo, Italy

Introduction: prescribing artificial dietary integration is of great help in supportingcancer patients who cannot meet their daily nutritional needs. The choice of integratorsshould be based not only upon their composition but also palatability, tolerance andcompliance by the patients. It is crucial in this respect whether patients considerartificial integrators as food rather than drug.

Methods: we administered a previously validated 8-questions questionnaire assessingthe view on artificial dietary integration, preferences and effects on physical andpsychological health to all consecutive patients with upper digestive tract and head-and-neck cancer sent for nutritional consultation, who had followed at least a 60-dayregimen of artificial dietary integration with home prescription according to theRegional directives.

Results: we interviewed 32 patients (18 males, 14 females), mean age 46 years, meanBMI 25 (range 15-32). Eighty percent of them was taking artificial dietary integrationtogether with their residual oral food intake, 20% as part of their total artificialnutrition. All patients responded to the questionnaire. Ninety-four percent of themconsidered integrators as important and reassuring; over 80% defined them as anadequate support to improve their general health and 90% was totally confident withthe specialist consultant. Patients who considered integrators drugs rather than foodshowed a longer a more consistent intake compliance.

Conclusions: Artificial dietary integrators are viewed by the patients as drugs,consistently with the European an local legislation that dictate their criteria of choiceand dosage and categorise them as drugs. Thus, indications, choice, modality ofprescription and assessment of correct use should be specific duties of nutritionalconsultant doctors.

D94 WOMAN, SEXUALITY AND CANCER: A COGNITIVE SURVEY

R. Manzo, C. Battiloro, F. Caputo, M. Gilli, D. Rocco, L. BrancaccioAzienda Ospedaliera Monaldi - Napoli

Owing to a number of physical and emotional reasons a cancer diagnosis changes -even if only temporarily - the sexual life as it happens in any living species struggling forsurvival. This work aims at investigating the physicians‘ opinion as regards sexualityand the difficulties the women patients may come up against during the diagnosticcourse. In the clinical experience the aspect concerning the sexual life are oftenrelegated to the second place and they are unlikely to be spontaneously expressed. Bothwomen patients and doctors find it difficult to tackle the ‘‘sexuality’’ theme. For thispurpose a double questionnaire was used for doctors and patients. It included all thoseaspects of sexuality following on an examination of an ad hoc questionnaire to bepersonally filled out. The questionnaire was given in two times to 100 patients affectedby lung, breast, and colon cancer, whose therapy provided for a multimodal treatment:chemotherapy and/or hormonotherapy as well as to 54 doctors (operating in therespective Department of Medicine, Oncology and Surgery of the patients under study)As to the questionnaire for physicians, by analysing the characteristic of the samplesubjects it appears that 51,8% is made up of oncologists, 25,9% of pneumologists and22,2% of surgeons. It was further observed that, even though physicians deemed ituseful to give patients clear and reasonable information about the pshychosexualtroubles correlated to cancer and its treatments, only 15% of the patients gotinformation about that. From the results it emerges that physicians avoid dealing withthis point for lack of time (33,3%) and for embarrassment (38%), the latter is noticedamong patients, too, when putting questions concerning sexuality. in general from thestudy it emerges that there are changes in the sex-relational life both in the immediatefuture and in the long run (six months).




Dow

nloaded from


D95 CANCER PAIN EVALUATION IN ELDERLY PATIENTS. DOESAGE INFLUENCE PAIN CONTROL IN CLINICAL PRACTICE?

A. M. Minisini, E. Rijavec, M. Cozzi, C. Andreetta, G. Pascoletti, B. Alessi,F. Puglisi, M. Divella, G. FasolaDipartimento di Oncologia e Clinica di Anestesia e Rianimazione AziendaOspedaliero-Universitaria

Background: Elderly patients may be at increased risk for cancer pain due tocomorbidities and functional reserve limitation. Moreover in these patients, side effectscan limit the use of analgesic drugs in clinical practice. Little is known in the prevalenceof pain in elderly cancer patients in Italy.

Aim of the study: To collect data on the prevalence of pain in elderly canceroutpatients.

Methods: The Italian version of the Brief Pain Inventory was submitted toa consecutive series of cancer patients attending our outpatients clinic to receiveanticancer treatment between 11th and 18th December 2006.

Results:Data on pain prevalence in 114 patients were collected; 75 patients were aged <70 (group A) and 39 patients were aged ‡70 years (group B). Median age in group Aand B was 61 (range 32-69) and 73 (range 70-84) years respectively. Patients presentedwith advanced disease in 63% and 82% of cases in group A and B respectively (ChiSquare p=0.03). Patients taking opioids were 4% and 15% in group A and B,respectively (Chi Square p=0.03). The median value of the average intensity of pain(Numeric Rating Scale - NRS) in group A and B was 0 (range 0-8) and 5 (range 0-9),respectively (Mann-Whitney p<0.001). At the moment of attending our clinic, elderlypatients presented with higher pain intensity than younger patients (median NRS value2 vs 0 respectively, Mann-Whitney p= 0.002).

Conclusions: Elderly patients may be at increased risk for cancer pain. Further effortsshould be done to ameliorate pain control in elderly cancer patients.

D96 THE INFLUENCE OF WEIGHT LOSS ON OUTCOMES INSQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECKUNDERGOING CONCOMITANT CHEMORADIOTHERAPY

G. Capuano*, A. Grosso*, P. C. Gentile**, F. Bianciardi**, A. Di Palma**,I. Pavese***, F. Satta***, G. Coiro***, M. V. Zoffoli***, F. Todi***, E. Burattini***,M. Tosti***, A. Palladino***, M. Di Palma****Clinical Nutritional Service, **Radiotherapy Unit, ***Medical Oncology Unit,San Peter FBF Hospital – Rome

Background: Malnutrition plays a key role in the morbidity of Squamous-CellCarcinoma of the Head and Neck (SCCHN) undergoing concomitantchemoradiotherapy (CCRT).

Aim: The aim of this study is to evaluate the influence of weight loss on outcomes inSCCHN undergoing CCRT.

Methods: 41 consecutive patients with locoregionally advanced SCCHN who werereferred to CCRT were enrolled. Criteria for eligibility also included: not comorbidity(diabetes, hepatic or renal failure) and a Karnofsky performance score of at least 60.Patients were ineligible if they had undergone surgery or had previously receivedradiotherapy or CCRT for head and neck or other cancer. All patients were counselledto follow an early and intensive nutritional program before, during and after CCRT:dietary counseling from baseline to the second week of CCRT, Enteral Nutrition (EN)via nasogastric tube (polyurethane 8 Ch) from the second week of CCRT to the oralnutrition resume, dietary counseling from nasogastric tube removal to the resume ofnormal food intake. Weight body was evaluated at baseline, at the end and 30 days afterCCRT completion.

Results: Recent and involuntary weight loss (median 4%, range 0 - 25 ) was observed in26 SCCHN patients (63%) before CCRT. 21 patients (51%) were compliant with thenutritional program proposed. Median EN was 26 days (range 10 – 93). All compliantpatients achieved their nutritional requirements, whereas only 10% of non-compliantpatients did. Weight loss > 20% (severe malnutrition) of usual weight significantlycorrelate with treatment interruption (Spearman test: r = 0.515, p = 0.001),infection risk (rr = 0.098, 95 percent confidence interval 0.013 – 0.712, v2 = 7.280,p = 0.007), hospital readmission rate (Spearman test: r = 0.553, p = 0.001) andsurvival within 30 days after oncological treatment completion (long rank test:z = - 2.420, p = 0.016).

D97 ANXIETY, DEPRESSION AND QUALITY OF LIFE IN PATIENTS(PTS) WITH SARCOMA DURING CHEMOTHERAPY

Antonella Boglione1, Ilaria Lombardi1, Paola Bergnolo1, Simona Chiado Cutin1,Cristiano Oliva1, Paolo Pochettino1, Manuela Ingui’1, Orietta Dal Canton1,Ferdinando Garetto1, Giancarlo Gino2, Elena Maria Brach del Prever3, AlfredoBerruti3, Alessandro Comandone1. Gruppo Piemontese Sarcomi1UOA Oncologia, Ospedale Gradenigo, Torino; 2ASO CTO-CRF-MariaAdelaide, Torino; 3Universita degli Studi, Torino

Background: Sarcomas frequently affect young-adult people who are planning theirfuture and in many cases are active in job. Therapies could cause changes, alsoirreversible, in body-scheme, in quality of life, in job capability and in family balance.

Aims This study seeks to characterize the psychological status of patients with sarcomaand to investigate the differences between this group of patients and a control groupwith other neoplasms.

Patients: characteristics Subjects were 58 pts undergoing chemotherapy (CT) forsarcomas (group A); control group were123 pts undergoing chemotherapy for othermalignancies (group B). None patient had advanced or metastatic disease.

Group A:median age 57 (18-71) 40 males, 18 females, 28 neoadjuvant, 30 adjuvant CT;43 soft tissue sarcomas, 9 osteosarcomas, 6 Ewing sarcomas. Group B: median age63 (42-81); 79 males, 44 females; 25 neoadjuvant, 98 adjuvant CT; 82 colon cancer,41 breast cancer.

Methods: The Italian version of Hospital Anxiety and Depression Scale (HADS)and Functional Assessment for Cancer Therapy-General (FACT-G) were administeredby psychologist for all subjects during CT.

Results: No significant differences were found in mean scores between group A and Babout HADS anxiety items. HADS Depression scores were significantly higher ingroup A (p 0.04). Patients with sarcoma showed worse physical and emotionalwell-being (p <0.0001) and better relation with physicians (p 0.007); no differencesabout social and functional well-being (FACT-G). Global QoL was better in group B(p <0.0001).

Conclusions: Pts with sarcoma are particularly frail probably because of their youngage and treatments side effects. They must be taken in care since the first treatments bya multidisciplinary team including psychologist in order to increase the adherence tothe therapy and to improve the quality of life. On the other, these pts are prone tobetter cooperate with doctors, nurses and care givers than pts affected from differenttumours.

D98 MANAGEMENT OF PHARINGO-LARYNGEAL NEOPLASTICBLEEDING WITH OCTREOTIDE. A CASE REPORT

Filippo ZerilliU.O. di Oncologia Medica, Az. Osp. S. Antonio Abate di Trapani

A 51 years old man suffering from squamous carcinoma of the retromolar trigonusdiagnosed in 2000, initially treated by retromolar trigonal resection and radiotherapy,had a second cancer of the pyriform sinus in 2004.

This cancer was thought to be non resectable so he had a palliative tracheotomy.In December 2004 he was treated with a platinum and fluorouracil based

chemotherapy followed with weekly paclitaxel at progression.On March 11th 2006 the patient was admitted to hospital because of a serious

pharingo-laryngeal bleeding and treated (without any improvement) with tranexamicacid and repeated blood transfusions (seven).

Therefore octreotide was added (at a dosage of 0.2 mg twice a day) and resulted ina sudden stop of the bleeding.

On March 16th 2006 the patient was discharged.His haemoglobin value was 10 g/dl.This case report needs further studies to evaluate the efficacy of this treatment in

a clinical trial and to explain the mechanism of action of octreotide in non oesophagealbleedings.

Because this therapy is obviously long lasting, octreotide LAR formulation could bethe best choice.

D99 THE ACUTE IMPACT OF CHEMOTHERAPY ON THECOGNITIVE AND EMOTIONAL DOMAINS AND ON QUALITY OF LIFEOF OLDER CANCER PATIENTS

*Elena Zafarana, �Giuseppe Mottino, *Sara Licitra, *Chiara Biagioni, **ElisaBianchini, *Andrea Ciarlo, *ElioMaria Vinci, �Dimitri Becheri, �Antonio Bavazzano,**Mauro Gasparini, *Angelo Di Leo, *Laura Biganzoli*U.O. Oncologia Medica, �U.O. Geriatria, Hospital of Prato; **CentroCoordinamento Sperimentazione Cliniche -C.S.P.O - Istituto Toscano Tumori

Background: There are data suggesting that chemotherapy may have a negative impacton cognitive function; on the other hand, aging itself causes changes in the cognitivedomain. This area is commonly evaluated in the context of a comprehensive geriatricassessment by the Mini-mental state examination (MMSE).

Aim: We conducted a pilot study to evaluate the acute effects of chemotherapy oncognition in elderly patients (age >70) affected by solid tumors and to evaluate its effecton quality of life and emotional domain.

Methods: Cognitive function was measured before chemotherapy start and at 12 weekswith a battery of neuropsychological tests administered to assess attention, memory,language, visuo-spatial ability, praxia, and general cognitive status. Quality of life andthe emotional domain were evaluated by the FACT-G questionnaire and the GeriatricDepression Scale, respectively.




ownloaded from


Results: A total of 30 patients, median age 76 (range 70-82) are evaluable. Baselinevalues of the tests are reported in the following table.

Test Baseline values:mean (sd)

Test Baseline values:mean (sd)

MMSE 27.5 (2.15) Token 30.2 (3.4)ClockDrawing 6.5 (2.86) Word fluency (category) 11.7 (4.38)Babcock’s Story 5.45 (1.7) Word fluency (letter) 20.26 (9.62)15 Words of Rey-RI 31.98 (11.01) Drawing 12.16 (1.83)15 Words of Rey-RD 7.64 (9.31) Attentive Matrix 45.82 (8.13)Corsi cube 3.86 (.76)

Data on changes in test scores after chemotherapy, as well as impact of chemotherapyon emotion and quality of life will be presented. These results will be the basis to designa more complete and adequately sized study.

D100 RENAL SAFETY OF PROLONGED I.V. ZOLEDRONIC ACID (ZA)ADMINISTRATION IN PATIENTS WITH BONE METASTASES

S. Turano, V. Liguori, S. Ceniti, R. Biamonte, R. DeSimone, A. Filice, C. Manfredi,C. Mastroianni, A. Rovito, C. Viscomi and S. PalazzoMedical Oncology Division,Cosenza,Italy

Background: The introduction of ZA, a new-generation bisphosphonate, has extendedthe use of bisphosphonates in the treatment of patients with bone metastases. Somestudies have shown renal toxicity associated with bisphosphonates, also following theexposure to ZA. Published literature suggests that renal function deterioration occursin 8.8-15.2% of patients at the recommended dose of 4 mg i.v. over 15 minutes.However, there are few data on the renal safety of i.v.ZA beyond 1 year ofadministration.

Methods: From January 2003 to December 2006, 24 bisphosphonate naıve patientswith bone metastases received i.v. ZA (4 mg over 15 minutes every 3-4 weeks) beyond 1year of administration.

Serum creatinine levels (SCL) were measured at baseline and before each infusion.Notable serum creatinine increases were defined as > 0.5 mg/dl.

Results: 25 pts with bone metastases (13 from breast cancer, 5 from prostate cancer, 3from colon-rectal cancer, 3 multiple myeloma, 1 from renal cell carcinoma,plurimetastases in 13 (52%)) were included. Median age at baseline was 66 y (range28-84 y), 41% of the patients were >70 years old, 16 female and 9 male were included .The median number of ZA cycles was 22 (range 12-57). 22 pts were receivingconcomitantly different chemotherapy regimes. The median SCL levels were:baseline: 0.85 mg/dl (range 0.5-1,4); during ZA infusion: 1.0 mg/dl (range 0.7- 2.2).A notable SCL increase was observed in 4 (16%) pts.7 pts discontinued treatment:2 due to SCL >2 mg/dl, 3 died from progressive disease, 2 died from symptomatichypocalcaemia.

Conclusion: i.v.ZA was safe and well tolerated by patients, including those who werereceiving cytotoxic therapies, and renal function was maintained, with a substantialfunctional independence and QoL benefit.

D101 TOMOTHERAPY FOR MENINGIOMAS: A REPORT OF TWOCASES

M. Motta1, A. Bolognesi1, E. De Martin2, E. Mazza4, L. Perna2, B. Longobardi2,A. Del Vecchio2, N. DiMuzio1, F. Fazio 1,3,5

1Dept of Radiation Oncology; 2Dept of Medical Physics; 3Dept of NuclearMedicine, 4Medical Oncology; Scientific Institute San Raffaele, Milano;5IBFM-CNR, University of milano Bicocca, Milano, Italy

Background: Several patients with benign brain neoplasm cannot undergoradiosurgical treatment with c knife because of the extension or the site of their lesion.

Purpose: to evaluate the feasibility of radical radiation treatment with TT formeningiomas located near critical structures (the optic pathways, the brainstem orboth).

Materials and methods: Two patients were treated with Helical Tomotherapy ( TT )in our Department. The first patient ( pts 1), a woman of 50, suffered froma meningioma located around the optic chiasm and the left optic nerve. She had biopsyin August 2005. The second patient ( pts 2) is a man of 56 who underwent 6 majorsurgeries since 1984 until April 2006 for removing a meningioma involving both theeye-sockets and surrounding the clivus, reaching the left maxillary sinus. He had anearly recurrence in June 2006. He showed blindness of the left eye, and III left cranialnerve palsy.

Results: It is possible to compare Tomotherapy with 3DCRT, as follows: - Opticchiasm : ( dose constraint: 50 Gy) : 43 vs 56 Gy for ‘‘pts1’’, 48 vs 55.8 Gy for ‘‘pts2’’; -left optic nerve Dmax (dose constraint: 55 Gy): 51.7 vs 56 Gy for ‘‘pts1’’; 48 vs 48.5 Gyfor ‘‘pts 2’’ - right optic nerve Dmax: 37.5 vs 55.9 Gy for ‘‘pts1’’, 54 vs 55.4 for ‘‘pts2’’.After 2 years follow up, ‘‘ pts 1’’ shows a stable disease at MRI, without any side effect.After 6 months," pts 2" shows a partial reduction of the lesion at MRI, without anyside effect.

Conclusions: TT is feasible for these neoplasms. Beyond the higher precision indelivering radiation treatment, an additional advantage is the daily megavoltage CT,to check the accuracy of set-up before each fraction.

D102 DIAGNOSIS COMMUNICATION IN CANCER PATIENTS: ACORRELATION BETWEEN DELIVERED INFORMATION ANDPATIENTS’ PERCEPTION AND REACTION

Federica Grande, Simonetta Chiara Stani, Luciano Pastore, Claudio Cianti,Germana Lizzani, and Umberto RecineDay Hospital Oncoematologico, Ospedale S. Spirito Roma

Background: Disease communication in cancer patients is of great importance. Muchof the behaviour of the patient in terms of trusting the physician, cooperation andcompliance with the disease and the treatment depends on the first approach.The mainendpoints of the present study were to evaluate 1)if the degree of delivered informationaccording to the physician corresponds to an equal degree in patients’ perception 2) ifthe depression/anxiety degree correlates to the level of delivered information.

Patients and methods: A communication expert (psycooncologist) took part assilent observer to each first visit performed in Day Hospital, then both patient andphysician were asked to undergo a private conversation with the psycooncologist andto fill in a questionnaire. Physician and psycooncologist were asked to indicate the levelof delivered information through a 5-step scale (very detailed, clear and adequate,general, without speaking of cancer, no information). The patient had to indicatehis level of comprehension (high, good, medium, low, nihil) and to fill the A-formof CBA-H.

Results: 47 patients (25 female, median age 63, mostly breast cancer and non-Hodgkinlymphoma) accepted to perform the test and to follow a programme of interviews withthe psycooncologist along the duration of chemotherapy. Delivered information was oflevel 1,2,3 in all cases. Patient’s comprehension was one level below in 75% of cases.Anxiety was lower in patient with ‘‘clear and adequate’’ information compared with theother levels of information. No depressive reaction was observed. Fear level appears tobe lower when detailed information about cure is delivered.

Conclusions: Our data suggest that clear and adequate information is better perceivedby the patient and generates a lower rate of anxiety compared with very detailedcommunication. Clear and adequate communication appears to be superior in terms ofrespect of patient’s psychological defences.

D103 UTILIZATION OF CONTROLLED-RELEASED OXYCODONE INONCOLOGICAL PATIENTS

A. Conti, P. Ballatore, A. PoggiHospice ‘‘My Life’’, Nepi(VT)

Background & Aim: The objective of this study was to evaluate the efficacy andtolerability of oxycodone CR in cancer patients.

Patients and methods: Forty-two patients, affected by several types of malignantdesease, associated with severe pain, were treated with oxycodone CR, some in hospitaland some at home. The average age of the enrolled patients was 65 years; 62% men,38% women.

Results: Naive patients started the therapy with a dosage of 20 mg/die; the otherpatients, already in therapy with opidoids, were administered the correspondingdosage according to the published conversion tables. The final average dosage was 100mg/die (range 40 - 360). The evaluation of pain, using NRS scale, showed a progressivereduction of the values throughout the weeks of the treatment passing from a value 8 toa value of 3,09, after 45 days of therapy (T0=8; T14=4,07; T45=3,09). The QoL,evaluated with a questionnaire FACT-G, described good results following thetreatment according to NRS survey, especially in patients in domicile regime. The sideeffects, occurred to 34 patients, were of light-moderate character with the tendency todecrease during the course of the study.

Discussion: Even if the number of the treated patients is not high, the results of thisstudy evidence how oxycodone CR can be considered the new ‘‘gold standard’’ in thetreatment of moderate-severe pain, as already evaluated from several authors.

D104 UNDERSTANDING CULTURAL AND EMOTIONAL FEATURESINFLUENCING THE CHOICE OF PARTICIPATING IN CLINICAL TRIALS

C. Catania, T. De Pas, A. Goldhirsch, D. Radice, L. Adamoli, M. Medici, E. Verri,C. Marenghi, F. de Braud and F. NoleEuropean Institute of Oncology

Background: The choice of whether to participate in a clinical trial by patients (pts)with cancer is influenced, beyond trial information, by important factors as patient’sown emotional and cultural properties, including past history as well as, prejudices.Our hypothesis was that a better knowledge of these might lead patients to a moreconscious motivation to make the choice. Moreover, tackling common prejudices or




Dow

nloaded from


fears might lead to improving written informed consent documents for several clinicalconditions.

Methods: A 17-items, multiple-choice and open-answer questionnaire was developedand administered to patients with advanced lung or breast cancer who have neverdiscussed participation in a clinical trial.

Results: The questionnaire was answered by all 102 pts who received it. Eighty-threepercent of pts were positive about their participation, regardless of having (68/78 pts)or not (19/24 pts) children and completing (70/79 pts) or not (17/23 pts) high-schooleducation. Trust in the investigator (75%) or in the Institute (68%) and hope to receivea new chance for cure (78%) were a major motivation for a positive answer. Fifty-eightpercent thought viewed participation in a clinical trial as a sign that no other‘‘standard’’ treatments are available; 24% were worried of unknown side effects and75% considered detailed information on expected toxicity to be helpful in makingthe decision. Eight percent of patients felt exploited as ‘‘guinea pigs’’ and 52% hada some degree of fear that a clinical trial is primarily motivated by economical interests.Sixty-seven percent of patients thought that an oral experimental drug can make easierthe participation in a clinical trial, being its easy use and having more freedom the mostimportant reasons for accepting.

Conclusion: Several hopes, prejudices and fears have been captured by thequestionnaire. Italian patients positively viewed participation in a clinical trial,which was regarded as a new chance for cure. Trust in the investigator or in theInstitute were a major motivation for a positive answer. These results might lead toa study on the effect of a specific intervention on informing patients about clinicalresearch.

D105 BUDGET: FROM A QUANTITATIVE TO QUALITATIVEOBJECTIVE

Olga Alebardi, Vittorio D. Ferrari*, Salvatore Grisanti*, Francesca Valcamonico*,Lucia Vassalli*, Giovanni Rangoni*, Patrizia Marpicati*, Elisabetta Montini*,Edda Simoncini*, Giovanni Marini*UMaCA, *U.O. Oncologia Medica, Azienda Spedali Civili, [email protected]

Aim: define a qualitative and quantitative budget to a Medical Oncology UnitThe demand for performances has been in constant increase in the year. The order of

an expense ceiling would not have contributed some term of appraisal of the recoveredefficiency and effectiveness of the service, because of the constant and importantincrease of the carried out performances.

Methods: The variables which contribute the cost for drugs were: -a) the cost of theactive principle – b) the packing cost – c) the yield for confection/cost milliliter net – d)production process rejection – e) Spin of the supplies in hand: Value of the warehousesfor drug/consumption drug. We has lead an analysis that has carried to one stablestructure of monitoring of the relative data to single drugs, on the followingparameters: - Cost mililiter net (it is come down with the centralized preparations) -Cost for treatment (which index of the recovery of efficiency of the process) – MonthlyValue of the consumptions – Monthly Value of the supplies. Such analysis has supplied:- a new value of reference for the effective and dynamic management control - a modelof management control in a process of continuous improvement.

Conclusion: Cost reduction on an annual basis was 25% " Percentage reduction of totalconsumption in the period of analysis was 4,6 %. Every years this innovative approachto the antiblastic drugs expense has been repeated so as to concur the better possibletreatment to every patient containing the costs treatment.

file admittance tot

2002 N of treatment 769 6017 67862003 N of treatment 1108 8107 9215

D106 TRACKING OUTPATIENTS’ SELF-REPORTED SYMPTOMSRELATED TO ANTICANCER TREATMENT TOXICITIES: BRIDGINGHOME AND HOSPITAL USING A WEB-BASED MODEL

Alessandro Follador1, Giuseppe Aprile1, Monica Noselli2, Emiliana Iaiza1, FedericaDe Pauli1, Gaetano Pascoletti1, Roberta Sottile1, Enzo Della Mea2, Fabio Puglisi1,Gianpiero Fasola 1

1Department of Oncology, University Hospital, Udine, Italy 2 Department ofInformatics, University of Udine, Italy

Background: Discrepancies appeared when traditional modalities in collectinginformation regarding toxicities suffered by patients being exposed to anticancertreatments have been compared to direct self-reports. Owing to the availability of easilyaccessible informatics technologies, we hypothesized that a Web-site could be anaccurate and reliable tool to directly record toxicity data.

Methods: A database schema was designed, implemented with MySQL databasemanagement system and interfaced with the Web by using Java 2 Enterprise Edition onthe Tomcat application container. A simplified, patient-adapted definition of type andNCI-CTCAE grade of the 15 commonest toxicities has been inserted into the databasefor reporting. The web site has two areas, both accessible only with username and

password, respectively devoted to patients and physicians. Through home Web access,each patient can report toxicities by choosing and grading any of them. Web siteusability has been tested by non-professional users with simulated scenarios. Aftera quick training, the users were asked to report the described toxicities. Time neededfor reporting and reporting errors have been recorded.

Results: The average time needed for entering a report has been 10 minutes. Userscorrectly reported the toxicities provided in the scenarios, but difficulties were noted inthe correct identification of the week when entering reports for two or more weeks oftherapy.

Conclusions: In order to track patient-reported toxicities we developed a prototypeWeb-based model. Potential utilities of the system are being tested to demonstrate: 1.Accuracy, allowing patients to easily report types and grades of the experiencedtoxicities. 2. Flexibility, consenting patient-reporting either weekly or on demand. 3.Capability to integrate and assemble with an electronic patient record anda computerized physician order-entry. The latter capability will be provided bya patient portal with secure authentication and access being developed by the Regionalhealthcare Authority. Comparative randomized analysis in 100 consecutive outpatientsbetween clinical interviewing and Web-reported toxicity has been planned.

D107 ORAL MUCOSITIS IN THE TREATMENT OF HEAD AND NECKCANCERS WITH RADIOTHERAPY OR RADIOCHEMOTHERAPY:PREVENTION, ASSESSMENT AND MANAGEMENT

Rosanna Mirabelli, Mariaquila SantoroDepartmento of Onco-Hematology, Ospedale Pugliese-Ciaccio 88100Catanzaro

Radiation therapy (RT) of head and neck cancers (HNC) is very often linked to severeside effects what interest the oral mucosa. Mucositis radio-induced is defined as thereactive inflammation of the oro-pharyngeal mucosa membrane during theadministration of radiotherapy. Radiation mucositis onset 1-2 week after the beginningof the RT and/or radiochemotherapy (RCT): has been brought (1) that around him80% of the patients can develop oral mucositis during a cycle of curative treatment.Additionally, the 34-43 % of the patients introduces a severe mucositis, grade 3 or 4.Oral mucositis (OM) has strong impact both on the delivery of treatment prescribedand on the quality of the life of the patients and can be a dose-limiting factor and in the9-19% of the patients it is necessary to interrupt the treatment for the onset ofmucositis. The mucositis is a process characterized by five steps: a) initiation, b)upregulation and message generation, c) signalling and amplification, d) ulceration,and, e) healing. At present the bio-molecular pathways that brings to the mucositisare unclear, the has been hypothesized to follow him of three different events in theoro-pharyngeal mucosa: 1) keranocyte toxicity and death, 2) impaired mucosalimmune surveillance, and 3) significant alterations in oral flora. In spite of thefrequency with which introduces him accord doesn’t exist around the assessment,prevention, management of oral mucositis.

Oral mucositis occurs more frequently in patients treated for cancer and its severitydepends from various factors: in patients irradiated the damage to oral mucosa iscorrelated to volume irradiated, fraction size, fractionation scheme, total dose andtype of ionizing irradiation utilized. With regard the prevention of the oral mucositisand the protection of normal tissue, the use of treatment tecnique like the 3D-CRT orthe IMRT can produce a best optimization of the dose to the target volume with savingof the normal tissues. For the measurement of the oral mucositis we have differentmethods, each of which introduces advantages and disadvantages. The early diagnosisof OM in partnership to the treatment of the local infection (candida, herpes infection)can reduce the damages to the mucosa and to minimize the ulcerative lesions. Inconclusion, numerous interventions (pharmacological and non- pharmacological)have been proposed for preventing or to take care of this frequent and devastatingcollateral effect of the anticancer therapies, but to the actual state any randomizeds trialhas shown a benefit of a specific modality. Insofar, are need more randomized studiesand with an enough number of patients to the purpose to resolve completely theseissues.

D108 THE CORRECT USE OF OPIOIDS IN PEDIATRIC ONCOLOGY:SWITCH FROM TRANSDERMAL TO OXYCODONE CR

salvatore criscuolousl 7 siena

Background&Aim: This case is about a thirteen year old child affected by leukaemiawith a strong pain located in the abdomen, vertebral column and at feet level, when invertical position.

Patients and methods: The previous treatment with acetaminophen and tramadoldidn’t have any efficacy so the doctor decided to prescribe morphine instant release.

Results: Also this new drug was not appropriate (suitable) and the child had to behospitalized because of an acute pain. During this period a 25 lg/h fentanyltransdermal patch was applied in conjunction with sub cutaneous morphine. Paincontrol was obtained only for one day; during the week end the child had several eventof breakthrough pain, controlled with intra muscle morphine. At this point, the doctordecided to increase fentanyl dosage up to 75 lg/h but since they didn’t obtain paincontrol, they switched to oxycodne CR, using conversion tables reported by literature.During the night, the child was affected by a comatose state, manifested with miotiche




ownloaded from


pupils. Probably the reason of this fact was the presence of circulating fentanyl. Withan adjustment of the dosage, resulting of 60 mg/die the following morning, the doctorobtained a good pain control with no side effects for a twenty day period. Withprogression of desease, oxycodone CR dosage was increased up to 80 mg/die until thedeath of the child.

Discussion: This study demonstrated the importance of a correct conversion fromdifferent oppioids and the right use of correct formulation. In fact, for an increasingpain, transdermal drugs are not advisable while the use of a drug that allows a dailyvariation of the dosage can represent the best solution. In particular, oxicodone CRdemonstrated to be a good drug for severe pain control with a good tolerability, also inchildren.

D109 ADJUVANT CHEMOTHERAPY IN PATIENTS WITH HIGH RISKSTAGE I NON SEMINOMA TESTICULAR CANCER

Franco Morelli1,Concetta Di Micco1, Valentina Boni1, Giuseppe Palomba1,Pasquale Setola2, Vittorino Ricci Barbini 2 and Evaristo Maiello 1

1Oncology Unit 2Urology Unit -IRCCS ‘‘Casa Sollievo della Sofferenza’’ SanGiovanni Rotondo

Introduction: Stage I non seminoma testicular cancer has a cure rate than 95% afterorchiectomy but 15% of patients with negative CT scan will have occult nodal spread.

Materials and methods: Since October 1991, 67 patients with stage I high risk nonseminoma testicular cancer were treated with 2 courses of standard BEP. They wereconsidered high risk cases because they had vascular invasion (21%), embryonalcarcinoma (30%) or both (49%).

Results: Median age was 28 years (range 18-53), serum pre-orchiectomy markers wereraised in 18%. Median time from orchiectomy to chemotherapy start was 34 days(range: 23-49). All patients are disease free and alive with a median follow up of 80months (range: 12-186). No grade 3-4 toxicity was seen except vomiting in 22% of thecourses. Myelotoxicity was mild: G1-2 neutropenia in 15% and anemia in 8% of thecourses. One case of bleomycin induced pulmonary fibrosis was observed.

Conclusions: Adjuvant chemotherapy is a safe and effective treatment in preventingrelapse in patients with high risk stage I non seminoma testicular cancer.

D110 FOTEMUSTINE IN RECURRENT OR PROGRESSIVEGLIOBLASTOMA MULTIFORME (GBM)

Savio G. Pepe A. Laudani A. Leonardi V. Usset A. Rondello G. Arcuri C. PalmisanoV. Alu’ M. Macaluso M. and Agostara BDepartment of Oncology – Oncology Hospital M. Ascoli – A.R.N.A.S. Civico -Palermo

Background: Recurrent or progressive Glioblastoma multiforme (GBM) is resistantto most therapeutic endeavors, with low response rates and survival rarely exceedingsix months . There are no clearly established chemotherapeutic regimens and the aimof the treatment is palliation with improvement in the quality of live.

Patients and methods: We reported a phase II trial in progressive or recurrentglioblastoma patients after surgery, standard radiotherapy and first line chemotherapytemozolomide based with Fotemustine. A third-genaration nitrosurea with highlipophilicity and better penetration through the cell membrane. The treatmentconsisted of three weekly infusion of Fotemustine 100mg/ m days 1-8- 15. If patientresponded to the treatment after a 5 weeks rest period, Fotemustine was continued atthe same dose but every three weeks.

Results: The primary endpoint was progression free survival, secondary endpointsincluded response rates quality of live and safety profile.

13 Glioblastoma Patients have been treated since March 2005. All patientscompleted induction period. In four patients were observed partial remission, in threepatients stable disease, in six patients were registered progression disease . Medianprogression free survival was 26 weeks ( range 6-48), median duration of response and/or stabilization was 20 weeks. The main toxicity was hematological, thrombocytopeniaand leucopenia.

Conclusion: Fotemustine seems to represent an acceptable safety profile, modestimprovement in quality of life.

D111 A.L.D.O (HIGH DOSE OXYCODONE): NEW SCIENTIFICEVIDENCES

Ferrarese Fabio, Becchimanzi Gioia, Bernardo Massimo, Conte Maria Anna, GioiaAngela*, Ottaviani Davide**, Palomba Rosa***Ospedale Ca’Foncello - Treviso; Cure Palliative,Terapia Antalgica, OspedaleCivile Pinerolo ; Serv. Cure Palliative, Osp. Bolzano - Bz ;Casa di cura ‘‘Pineta delCarso’’, Aurisina - Trieste ;Terapia Antalgica, Ospedale S. Chiara - Pisa*;Ospedale Molinette - Torino**; AOU Federico II Napoli***

Background & Aim: Uncontrolled pain is one of the most important problems thatdoctors have to fight every day. Recent studies have demonstrated that with the use ofhigh doses of oxycodone CR it is possible to obtain a good control of pain associatedwith a good quality of life.

An Italian study on 99 patients demonstrated that 224 mg/die oxicodone CR gave anNRS= 2,7 with poor side effects.

Patients and methods: The aim of this study was to reproduce the Italian experience,increasing the number of the evaluated patients. One hundred and seventy patients(average age 64), were enrolled. Sixteen patients were affected by non cancer diseaseswhile all the others were cancer patients mostly affected by lung cancer (21,3%), breastcancer (13%), prostate (10,6%), pancreas (9,46%) and uterus cancer (6,5%). Only 14%of these patients, treated with 231 mg/die oxycodone CR for 31,85 days, had goodcontrol of pain. Most of the other drugs used were either not suitable for the patients orthe dosage was not appropriate. The NRS evaluated at the beginning of the study was7,75. Patients reported pain as follows: 45,8% in a period from 0 to three months oftreatment, 33,4% from three to six months and 20,8% over a period longer than sixmonths.

Results: All patients were treated with oxycodone CR at a final average dosage of220 mg/die for 68,91 days. A final NRS resulted 2,78. The 58,8% of patients witha stable dosage, declared no side effects. The 5,8% patients declared serious side effects,such as stipsi, spleepiness and anxiety but nobody suspended the treatment. The otherpatients declared the typical side effects of the class of opioids.

Discussion: This study confirmed the previous international and Italian analysis aboutthe correct use of high doses of oxycodone CR for cancer and non cancer pain controlalso for a long period, with a good quality of life and a good compliance.

D112 EVALUATION OF PSYCHOLOGICAL DISTRESS, ANXIETYAND DEPRESSION IN ONCOLOGIC PATIENTS: A SINGLE CENTEREXPERIENCE

Barbara Buralli1, Salvatore Manai1, Andrea Camerini2, Olimpia Siclari2, ChetiPuccetti2, Sara Donati2, Gianna Tartarelli2, Chiara Valsuani2, Domenico Amoroso 2

1 U.O.C. di Psicologia, 2 U.O.C. di Oncologia Medica, Istituto Toscano Tumori,Ospedale Versilia, Lido di Camaiore (LU)

Background: Psychological status influence patients’ compliance to treatments, qualityof life and perhaps final outcome. The screening for psychological disturbance mayallow patients at risk to be identified.

Methods: 133 consecutive pts (76 F, mean age 63.7 ± 11.6 yrs) admitted to our MedicalOncology Unit were evaluated at hospital admittance. We employed the Italianvalidated version of the Hospital Anxiety Depression Scale (HADS) questionnaire,a self-administered questionnaire specifically developed to reveal states of distress (D),anxiety (A) end depression (DE) in non-psychiatric patients with organic disease. Twocut-off values (7 and 11 points) to identify borderline (8-10 points) and probableclinically relevant cases (‡11 points) in A and DE scales were used. Scores ‡21 wereconsidered to be of clinical relevance in D scale.

Results:Mean D, A and DE levels were 16.5 ± 11.6, 7.8 ± 4.7 and 8.3 ± 5.3 respectively.Females showed higher levels than males for all parameters (D: 17.6 ± 9.5 vs 14.2 ± 8.1,p=0.031; A: 8.6 ± 4.9 vs 6.9 ± 4.2, p=0.035; DE: 9.1 ± 5.6 vs 7.3 ± 4.7, p=0.06ns). Age-related subgroup analysis demonstrated a trend towards higher A scores in £40 yrspts vs total population (11.0 ± 3.0 vs 7.8 ± 4.7, p=0.08ns) and significantly higher Dand DE values in ‡80 yrs pts (22.6 ± 11.3 vs 16.2 ± 9.1, p=0.05 and 13.0 ± 6.6 vs 8.3 ±5.3, p=0.025 respectively). Regression analysis showed in females a significant directcorrelation between age - D (r = +0.46, p = 0.048) and age - DE (r = +0.62,p = 0.0019) and in males a significant inverse correlation between age - D(r = -0.52, p = 0.04), age - A (r = -0.45, p = 0.05) and a trend between age - DE(r = -0.42, p = 0.07ns).

Conclusions: Study population presented with borderline admittance D, A and DEvalues. Young males respect to A and old women respect to D and DE represent higherrisk groups for future development of psychological abnormalities complicatingdisease treatment.

D113 TREATMENT OF PAINFUL SYNDROMES WITH CONTROLLEDRELEASE-OXYCODONE IN HEMATOLOGIC PATIENTS

Cartoni Claudio, Brunetti Gregorio, D’Elia Gianna Maria, Niscola Pasquale*,Conti Alessandra§, Favale Enzo, Alfieri Pierluigi Arbana Dizdari^

Ematologia Azienda Policlinico Umberto I, Roma, *Ematologia, Ospedale S.Eugenio, Roma, §Hospice My Life, Viterbo, ^Ematologia Policlinico S. OrsolaBologna, Dipartimento di Onco-Ematologia –Universita di Modena

Background & Aim: Many malignant hematological malignancies record the presenceof numerous painful syndromes, not answering to the employment of anti-inflammatory or antiepileptics drugs. Aim of this study has been to estimate theeffectiveness of an opioid drug (CR-oxycodone) in the treatment of pain from differentcauses.

Patients and methods: 31 pts.(47,%) were affected by multiple myeloma 14 (21%)lymphoma, 17 (26%) leukaemia and 3 (5%) other syndromes; pain was caused bylocalization of malignant disease in 29 patients (44,6%), iatrogenic toxicity in 24patients (37%), Herpes Zoster neuropathy in 4 patients (6%), opportunistic infectionsin 7 patients (11%) and several causes in one patient (1,4%). Pain intensity wasevaluated by using the numerical rating scale (NRS) along with the global patientevaluation of efficacy (GPE). CR Oxycodone was started at 10 mg bid and titrated withoral morphine. The 97% of patients had previous treatment judged not effective




Dow

nloaded from


(22,9% strong opioids, 26,3% week opioids, 24,5% NSAIDs, 21,1% anticonvulsivants,5,2% others).

Results: The treatment period was 14 days; average NRS 7,56 at basal time, 3,81 on day3, 1,9 on day 7 and 0.98 on day 14. All the patients have been treated with an averagedosage of 32,91 mg/die oxycodone CR (range 20 – 80 mg/die). GPE was valuated good/excellent in 79,2% of patients, satisfactory in 7,3% and unsatisfactory in 3,5% (10 % ofpatients didn’t respond). Rescue doses were administered in 80% of patients duringfirst week of treatment while only 25% used rescue dose during the third week. Inparticular, 18,6% of used drugs was NSAIDs 18,7% weak opioids and 62,7% strongopioids. The side effects remarked were of poor intensity; only a patient has suspendedthe treatment.

Discussion: Oxycodone CR has confirmed of being an effective drug in the treatmentof pain correlated to hematological tumors.

D114* SORAFENIB IN ADVANCED RENAL CELL CANCER: FINALRESULTS FROM A SINGLE INSTITUTION EXPERIENCE

Giuseppe Procopio, Elena Verzoni, Roberto Bajetta*, Maddalena Mancin, SaraPusceddu, Laura Catena, Sara De Dosso, Arpine Gevorgyan, Nicoletta Zilemboand Emilio BajettaMedical Oncology Unit, Pharmacy Unit, Fondazione IRCCS Istituto Nazionale deiTumori, Milan, Italy

Background: sorafenib (Nexavar�) is an oral multitargeted tyrosine kinase inhibitorof RAF-kinase and VEGFR2, with antiangiogenic and antitumor activity in pretreatedadvanced renal cell cancer (RCC).

Methods: In our institution from December 2005 to November 2006, 136 consecutivepatients(pts) with advanced RCC received sorafenib 400mg/bid/continuously. Mainpatient characteristics were: clear-cell cancer 107pts, papillary-cell 15pts, cromophobe-cell 3pts, Bellini ducts carcinoma 3pts,sarcomatoid variant 3, other hystotypes 5 pts.Previous nephrectomy was performed in 126pts with median relapse free survival of 23months (range 3-180mos). The most common site of disease was lung, whereas 97ptshad 2 or more secondary disease locations. According to Motzer’s prognostic score90pts were at low risk, 36pts and 10pts at intermediate and high risk respectively. 15 ptswere treatment naıve for metastatic disease. 69 and 52pts received one or at least twosystemic treatments respectively.

Results: currently130pts are evaluable for safety and efficacy. According to the RECISTcriteria, the activity of sorafenib in terms of tumor shrinkage was observed in39pts(31%) with 10 partial response (7.5%) and 29 minor response(24%) respectively.Stable disease was seen in 79pts (58%) and progression disease in 37 pts(27%),10 ptswere not evaluable for response. Overall, 89pts(65%) had a disease growth control.Median duration of response was 8 months and median time to progression was6.5mos, median overall survival time was 14 months.

The most common treatment- adverse events seen in 91% of pts, were grade (G)1/2(NCI-CTC) and included hand foot syndrome, rash, diarrhea, fatigue, hypertensionand mucositis. Dose modification due to G3-4 adverse event, such as skin toxicity andcardiovascular events, was performed in 52pts(39%).

Conclusion: sorafenib is effective in terms of tumor growth control in untreatedas well as in pretreated patients and in different hystotypes of renal cell cancer.Particularly, in heavily pretreated patients the number and severity of drug relatedtoxicity suggests the dose reduction as possible standard therapy. Authors thank datamanagement service of Italian Trials in Medical Oncology (I.T.M.O.) for theirassistance in preparing the manuscript.

D115* BEVACIZUMAB PLUS IMMUNOTHERAPY, WITHINTERLEUKIN-2 (IL-2) AND INTERFERONE-a (IFN-a), PLUSCHEMOTHERAPY (BIC), IN PATIENTS WITH METASTATIC RENALCELL CANCER (mRCC). DOSE-FINDING/PHASE II TRIAL

Sebastiano Buti, Silvia Lazzarelli, Cecilia Simonelli, Silvia Venturini, SimonSpazzapan, Giovanni Lo Re, Rodolfo Mattioli, Matteo Dalla Chiesa, MatteoBrighenti, Giancarlo Mazza, Rodolfo PassalacquaIstituti Ospitalieri Cremona

Background: Treatment with IL-2 and IFN-a is considered as an effectiveimmunotherapy (IT) for mRCC. Bevacizumab (B) proved to have efficacy withdifferent mechanism as regards as IL-2 + IFN-a, and had at least an additive effect withchemotherapy (Ch) in many tumors. On this basis, it is reasonable to search fora synergism between B, IT and Ch.

Methods: This is a multicenter dose-finding/phase II study aimed at to investigate: 1)safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD)of the BIC combination; 2) antitumor activity. Dose-finding study comprised 5escalation dose levels of Ch: Gemcitabine (G) (initial dose 600 mg/m2 to 1000 mg/m2)followed by 5FU bolus (initial dose 400 mg/m2 to 600 mg/m2) each one on days 1 and8 every 28 days, associated with fixed doses of B (10mg/kg on days 1 and 15), IL-2(1 MUI/m2 bid sc on days 8, 9, 15, 16 and 1 MUI/m2/day sc from days 10 to 12 andfrom 17 to 19) and IFN-a (3 MUI sc on days 10, 12, 17, 19). Three patients wereenrolled at each dose level according to Fibonacci statistical method. Phase II studyused the reached MTD and was conducted according to two stage Minimax Simondesign. Treatment was repetead for a maximum of 6 cycles followed by a maintenancetherapy with B and IT until progressive disease (PD).

Results: 36 patients were enrolled (male 75%); median age 58 years (range: 28-75):of these, 23 were assessed for toxicity, 14 were pre-treated and 9 not; there was 1 caseof DLT (2 level) due to a transitory grade 3 transaminases rising; phase II used thehighest dose level of Ch. Grade 3-4 toxicity during all cycles included: neutropenia nonfebrile (11/23) and 1 febrile, fever in 5; grade 3 toxicity included: thrombocytopeniain 7, asthenia in 4, hypertension in 2, anemia in 2; no bleeding of grade 3-4. So far thereare 29 assessable patients for response: 9 (31%) partial response, 12 (41%) stabledisease and 8 (28%) PD for an overall disease control rate of 72%.

Conclusion: This is the first study that explored the synergy between antiangiogenictherapy, IT and Ch in mRCC. The BIC combination is generally well tolerated andshows promising activity. The Phase II study is currently ongoing and accrual is stillopen.

D116* CXCR4 EXPRESSION IN RENAL CELL CARCINOMA: TODAYA PROGNOSTIC FACTOR, TOMORROW A NEW TARGET OFTHERAPY?

A. La Mura1, A. M. Grimaldi1, P. Fedelini2, G. Capasso3, D. Masala2, O. Nappi3,S. Scala4 and G. CartenI11Division of Oncology, 2Division of Urology, 3Division of Pathology, AORN‘‘Cardarelli’’, Naples

Background: Renal cell carcinoma (RCC) represents 3% of all malignancies. One thirdof RCC patients is metastatic at the diagnosis. Recent evidences suggest thatchemokines and their receptors, expressed even in RCC, play roles in cancermetastatization. CXCR4 is an inherent feature of RCC, as mutation of the VHL growthsuppressor gene results in overexpression of several proteins mainly CXCR4. CXCR4expression was evaluated in kidney cancer patients eir to further define the stage ofdisease adding prognostic factors, either to identify predictive biomarkers of clinicalresponse.

Methods: 198 RCC patients receiving primary surgical treatment and observedbetween 1999 and 2005 at Cardarelli Hospital were evaluated: 121 males, 77 females,age range 24-81, median 58 years, 149 clear renal cell carcinomas, 32 papillarycarcinomas, 8 chromofobe type renal cell carcinomas, 4 sarcomatoid renal cellcarcinomas and 5 renal cell carcinomas with mixed histologic aspects, with variableFuhrman’s nuclear grade and tumor (T) stage. CXCR4 immunohistochemistry is theprimary objective of our study. Each sample of RCC will be evaluated by twoindependent pathologists (O.N., A.L.M.)

Results: Primary endpoint will be to evaluate CXCR4 expression and to compare itwith known prognostic factors, such as Fuhrman’s nuclear grade, hystolopathologictype and T stage (according to AJCC sixth edition, 2002). Second endpoint will be thedetermination of disease progression and overall survival in the patients of the study.

Conclusions: CXCR4 expression could correlate with histopathologic recognizedprognostic factors and poor prognosis and be an useful marker to identify high riskpatients. The study is ongoing and results will be soon available.

D117* EGFR IN CLEAR CELL RENAL CARCINOMA: CORRELATIONBETWEEN GENE COPY NUMBER AND PROTEIN EXPRESSION

Paolo Cossu-Rocca1, Francesca Pili1, Davide Adriano Santeufemia2, AntonellaFesta1, Marcella Contini1, Gian Mario Soggiu1, Giovanni Maria Fadda2, CarloPutzu2, Antonica Mura1, Giovannino Massarelli1, Antonio Farris2

Istituto di Anatomia Patologica1, Cattedra di Oncologia Medica2, Universita diSassari

Background: Epidermal growth factor receptor (EGFR) is frequently overexpressed inclear cell renal carcinoma (CCRC) and is related with tumour development andgrowth. Thus, it represent not only a possible prognostic marker, but also a rationalmolecular target for selected anticancer drugs. Aim of the study was to evaluateexpression of the EGFR protein in patients with CCRC, to identify EGFR gene copynumbers, and to find out whether the protein overexpression is associated with theEGFR gene amplification.

Patients and methods: Histological sections from formalin-fixed, paraffin-embeddedtissues of 37 patients submitted to radical nephrectomy for CCRC were collected. Theexpression of EGFR protein was evaluated by immunohistochemistry, copy numbersof EGFR gene and chromosome 7 centromeres were investigated by fluorescencein situ hybridization (FISH). EGFR expression was detected as membranous andcytoplasmic staining of neoplastic cells >1% and a ratio between gene/centromericsignals of more than two was considered to indicate gene amplification. Mean numberof centromeric signals per nucleus was also scored to evaluate polysomy forchromosome 7.

Results: We found variable EGFR expression in all 37 cases (100%), while EGFR geneamplification was not detected in any of the cases by FISH. Polysomy of chromosome7 was observed in 24 cases (64,8%), and was not significantly correlated with EGFRexpression. However, polysomy correlated with advanced disease (p=0,02) and highFuhrman grade (p=0,01).

Conclusions: We did not find any correlation between EGFR gene amplification,polysomy of chromosome 7 and EGFR protein overexpression. Thus, increase in EGFRgene copy number should not be considered as an underlying genetic mechanism forEGFR overexpression in CCRC.




ownloaded from


D118* ADJUVANT LOW-DOSE INTERLEUKIN-2 (IL2) PLUSINTERFERON-ALPHA (IFN) IN OPERABLE RENAL CELL CANCER(RCC). A PHASE III, RANDOMIZED, MULTICENTER, INDEPENDENTTRIAL OF THE ITALIAN ONCOLOGY GROUP FOR CLINICALRESEARCH (GOIRC)

Rodolfo Passalacqua1, Carlo Buzio, Domenico Potenzoni, Sebastiano Buti,Roberto Labianca, Camillo Porta, Pino Nastasi, Ermanno Rondini, RobertaCamisa, Roberto Sabbatini, Fabrizio Artioli, Federico Alberici, CristianoBongiovanni, Debora Pezzuolo, Caterina Caminiti1Oncology Division, Istituti Ospitalieri, Cremona and other Italian Oncology andUrology Institutions

Background: For pts with non-metastatic RCC, no standard adjuvant treatment exists.Immunotherapy (IT) using IFN and/or IL2 is effective in metastatic disease setting.Low and chronically repeated doses of IL2 plus IFN induce a persistent stimulation ofthe immune system with no relevant toxicity.

Methods: From July1994 to March 2006, surgically treated RCC pts were randomizedto the following arms: A) low-dose IT; B) control arm. IT consisted of a 4-week cycle ofs.c. IL2 (5 days/wk, 1 million UI/sqm bid d 1,2 and 1 million UI/sqm x 1 d 3,4,5) + IFN(1,8 million UI/sqm d 3,5 of each week). Cycles were repeated every 4 months for thefirst 2 years and every 6 months for the remaining 3 years. Each patient received 12cycles in 5 years. Inclusion criteria were as follows: histological diagnosis of RCC, age<75 yrs, radical or partial nephrectomy within the past 3 months, pT1 (diameter of T >2,5 cm), T2, T3 a-b-c; pN0-pN3, M0; good cardiac and renal function and noautoimmune disease. Based on a planned sample size of 320 pts, the trial was designedto have a 80% power to detect a 15% improvement in 5-year survival.

Results: A total of 310 pts were randomized: 157 on arm A, 153 on arm B. Ptscharacteristics were well balanced between the two arms. At a median follow-up of 52months, 77 pts relapsed: 35 in arm A and 42 in arm B. In the first 5 years of observation,disease free survival (DFS) curves were similar in the two arms, but diverged thereafter.DFS at 5 and 10 years was 0.73 and 0.73 in arm A vs 0.73 and 0.60 in arm B with anestimated Hazard Ratio (HR) of 0.84 (95% CI: 0.54-1.33 p=0.47). Efficacy of IT wasmore evident in patients with good PS (HR 0.78; 0.47-1.30 p=0.35); age<60 yrs (HR0.61; 0.31-1.19 p=0.15), and low tumor grade (HR 0.70; 0.38-1.27 p=0.24). As foroverall survival, 59 deaths were observed with no differences between the two arms.Toxicity was mild and limited to WHO grade 1 or 2 in the majority of cases.

Conclusions: Low-dose adjuvant IL2+IFN is feasible in RCC and seems to reduce therisk of recurrence after 5 years from diagnosis. Follow-up update is still ongoing.

D119* PHASE II CLINICAL TRIAL OF METRONOMICCYCLOPHOSPHAMIDE (CTX) PLUS CELECOXIB (C) ANDDEXAMETHASONE (DEX) IN ADVANCED HORMONE REFRACTORYPROSTATE CANCER (HRPC): PRELIMINARY CLINICAL ANDPHARMACODYNAMIC RESULTS

Fontana A1, Bocci G2, D’Arcangelo M1, Galli L1, Fontana E1, Galli C1, Landi L1,Fioravanti A2, Orlandi P2, Barletta M1, Di Marsico R1, Barsanti G3, Andreuccetti M1,Del Tacca M2, Falcone A1,4

1Division of Medical Oncology, Civil Hospital of Livorno. 2Division ofChemotherapy and Pharmacology, Department of Internal Medicine, Universityof Pisa. 3Division of Medical Oncology, Lucca Hospital. 4University of Pisa, Italy

Background: Low-dose metronomic CTX and C have demonstrated a significantantiangiogenic activity in preclinical studies. Moreover, a single infusion of maximumtolerated dose chemotherapy, given before metronomic treatment, can increase itsantiangiogenic activity.

Methods: A total of 27 patients with advanced HRPC received CTX 500 mg/sqm iv day1 and CTX 50 mg po daily, DEX 1 mg po daily and C 200 mg po BID continuously,starting from day 2. Primary end point was activity (PSA reduction >50%); secondarywere: objective responses, toxicities (NCI-CTC criteria), PFS, OS, evaluation of plasmalevels of thrombospondin-1 (TSP-1), VEGF, sVEGFR-2, VE-cadherin mRNA;expression and synthesis of TSP-1 and VEGF in peripheral blood mononuclear cells.Patients (pts) characteristics: median age 74.5 years (54-91), median PS 1 (0-2), medianbaseline PSA 73 ng/ml (9.69->5000); main sites of disease: bone 22 pts (81,5%),lymphnodes 10 pts (37%); previous chemotherapy 20 pts (74,1%),

Results: 27 pts are evaluable for toxicity and response. Overall PSA decrease ‡ 50% wasfound in 9 pts (33,3%). Median time to PSA progression was 3,2 months (95% CI 2,7-3,7 months) and median OS was 20,9 months (CI 95% 14,5-27,3 months). No G3-4

hematologic or non-hematologic toxicities have been observed. Preliminarypharmacodynamic data indicate that a significant difference was observed in TSP-1 andVEGF levels between responders and non responders pts at day 84 of treatment.Indeed, the responders showed a significant increase of TSP-1 plasma concentrations(163.7±22.3% at day 84 vs. 100% at day 0; P<0.05) and a concomitant significantdecrease of plasma VEGF levels (29.8±11.7% at day 84 vs. 100% at day 0, P<0.05),whereas the non responders showed a marked increase of both plasma TSP-1 andVEGF levels.

Conclusions:Metronomic chemotherapy with CTX plus DEX and C in pts with HRPCshowed promising activity without relevant toxicity; interestingly, patients whoresponded to this metronomic schedule showed a concomitant increase of theendogenous inhibitor of angiogenesis and a decrease of a pro-angiogenic factor.

D120* CORRELATION OF 11C-CHOLINE PET AND PSA VALUES INPATIENTS WITH PROSTATE CANCER AND BIOCHEMICAL RELAPSEAFTER PRIMARY TREATMENTS

C. Ortega1, R. Vormola1, F. Montemurro1, S. Cirillo2, M. Petracchini2, P. Gabriele3,G. Muto4, M. Aglietta1

1Medical Oncology, 2Radiology Dept, 3Radiation Therapy, -Institute for CancerResearch and Treatment, IRCC, Candiolo (Turin)

Background: 11C-choline PET has demonstrated promising results in the evaluation ofsuspected recurrence after a primary treatment in prostate cancer (PC) patients (pts).However many authors recommend not performing 11C-choline PET for rising PSAvalues <5 ng/ml in pts with asymptomatic biochemical relapse (BR). The aim of ourstudy was to evaluate if there is a PSA cut-off that significatively correlates to 11C-choline PET positivity.

Methods: 84 pts with rising PSA after primary treatment underwent 11C-choline PET.Median age was 69 yrs (range 43-84). Median PSA at the time of PET scan was 3.4 ng/ml (range 0.12-176.00). Primary treatments were: 30 (36%) radical prostatectomy(RP), 31 (37%) external-beam radiation therapy (EBRT), 15 (18%) RP + adjuvantEBRT, 8 (9%) hormonal therapy.

Results: 11C-choline PET was positive in 54/84 pts (64%) and negative in 30/84 (36%).We found a statistically significant difference in the median PSA values betweenpatients with negative (median PSA: 1.13 ng/ml - range 0.12-6.47) and positive(median PSA: 5.38 ng/ml - range 1.33-176.00) PET scan findings (Mann-Whitney UTest. p< 0.001). No positive uptake was seen in pts with PSA <1 ng/ml (13/84); all ptswith PSA >6.5 ng/ml had a positive finding; for PSA values between 1 and 6.5 ng/ml(49/84), 11C- choline PET showed a pathological uptake in 32 pts. The ReceiverOperative Characteristic (ROC) analysis found that a PSA cut-off of 2.31 ng/ml hasa sensitivity of 90.7% and a specificity of 83% with respect of 11C-choline PETpositivity.

Conclusions: Above PSA cut-off value > 2.3 ng/ml our data suggest that PET scanmay be a useful tool to detect early recurrence. In agreement with other previousfindings, even if further data are needed, we don’t recommend PET scan in pts withPSA <1 ng/ml.

D121* THE IMPACT OF FIVE DIFFERENT ADMINISTRATIONINTERVALS ON THE PHARMACOKINETICS (PK) OF PACLITAXEL(PTX) AND PEGYLATED LIPOSOMAL DOXORUBICIN (PLD)COMBINATION

Luigi Cattel1, Paola Milla1, Eleonora Cerutti1, Fulvia Pedani2, Mario Airoldi2,Alice Crova2

1Drug Science and Techn Dept, University of Torino, Italy; 2Med Onc DeptH. San Giovanni A.S, Torino Italy

Background: The PTX-PLD association is a promising schedule for recurrent head/neck cancer. Their pk behavior could be dependent not only on PTX excipientinterference, but even on different i.v. administration intervals between the two drugs.This study evaluated any possible administration interval-dependent pk interaction,when PLD infusion started 0,1,3,12 or 24 h after PTX infusion end.

Methods: 30 patients, affected by recurrent cisplatin pre-treated squamous cell head/neck cancer, were randomized to receive PTX 80 mg/m2 q1w and PLD 12.5 mg/m2 q2wat intervals of 0,1,3,12 or 24 h. Pk parameters were evaluated by non-compartmentalanalysis, while statistical analysis was performed by non-parametric Kruskal Wallis test.

Results: median pk parameters are reported on table.

Admin. interval PTX PLD

0h 1h 3h 12h 24h p 0h 1h 3h 12h 24h p

Cmax (mg/l) 0.26 0.40 0.76 0.61 0.41 0.042 5.11 6.71 6.08 6.92 6.86 0.121AUCtot (mg/l*h) 0.87 1.57 4.67 4.29 3.36 0.005 676.4 606.8 749.6 723.8 739.6 0.515Kel (h

�1) 0.39 0.26 0.19 0.02 0.11 0.003 0.007 0.008 0.007 0.008 0.007 0.613Cltot (l/h) 153 92.5 28.7 32.2 41.7 0.005 0.031 0.036 0.029 0.030 0.029 0.681




Dow

nloaded from


PTX pk profile is strongly affected by PLD administration. PTX total exposure ishighly reduced, with a consequent increase in Cltot. On the other side, no statisticallysignificant interactions affected PLD pk parameters. Some in vitro experiments indicatethat PLD is able to partially absorb PTX, driving to PTX plasmatic concentrationreduction, when PLD is administered at 0-1h interval

Conclusions: PLD liposomal components seem to be able to entrap PTX, thereforereducing PTX plasmatic concentrations. In order to avoid pk interaction, the i.v.administration interval between PTX and PLD had to be 3 h at least. For shorterinterval, patients could be underexposed to PTX, with lesser clinical efficacy.

D122* FEASIBILITY AND ACTIVITY OF DOCETAXEL, CISPLATINUMAND 5-FLUOROURACIL (TPF) INDUCTION CHEMOTHERAPYFOLLOWED BY CONCURRENT CHEMO-RADIOTHERAPY(INCLUDING IMRT) IN LOCALLY ADVANCED NASOPHARYNGEALCANCER (LANPC)

Cristiana Bergamini1, Paolo Bossi1, Ester Orlandi2, Locati Locati1, CeciliaLiberatoscioli1, Carlo Fallai2, Mauro Palazzi2, Patrizia Olmi2, Lisa Licitra1

1Istituto Nazionale Tumori, Medical Oncology, Milan, Italy 2Istituto NazionaleTumori, Radiotherapy, Milan, Italy

Purpose: The role of induction chemotherapy (CT) in LANPC is debatable. It obtainsan high rate of response without proven significant survival benefit. Adjunct of taxaneto platinum and fluorouracil primary CT resulted in higher response rate and survivalin head and neck cancer. We tested the feasibility and activity of induction TPFfollowed by concomitant chemo-radiotherapy (cCRT) in LANPC.

Materials/Methods: From October 2004 to November 2006 twenty-four patients (pts)with LANPC (23 undifferentiated and 1 squamocellular cancer) were treated at ourInstitution with 1 to 4 cycles (median 3) of induction TPF (docetaxel 75 mg/sm andcisplatinum 75 mg/sm on day 1, and 5-fluorouracil 750 mg/sm/day for 96 and 120 hrs).Following TPF all pts received full doses radiotherapy (IMRT in 71%) concurrent withtri-weekly cisplatin 100 mg/sm. Nine (37%) pts were in Stage III and 14 (58%) in StageIV.

Results: Main toxicity of TPF consisted in neutropenia (21% G3; 8% G4, with 1 ptdeveloping a severe lung infection). Overall response rate to induction CT was 83%,while the remaining 17% obtained stable disease or minimal response. Radiotherapydose ranged from 66 to 70 Gy, with split course of 2 Gy for 1 patient. Grade 3-4 toxicityduring cCRT consisted in neutropenia (33% G3), febrile neutropenia (16% G3),mucositis (21% G3; 21% G4). Feeding tube was placed in 33% of pts.Median platinumdose intensity during RT was 83%, with 4 pts shifting to carboplatin due to G1 (2 pts)and G2 (2 pts) renal function impairment. Overall response rate in 20 fully evaluablepts was 95%, while 1 pt obtained a stable disease. Significant late toxicity consisted inxerostomia G3 in 29% of pts, neurotoxicity G3 in 4%.

Conclusions: In LANPC induction TPF followed by cCRT is feasible. High responserate to induction therapy as well as to full treatment was achieved. Promising results ofthis treatment schedule needs further exploration. Prolonged follow–up is needed toassess long term toxicity. Supported in part by AIRC.

D123* CETUXIMAB (C-MAB) AND CHEMO-RADIATION FORLOCO-REGIONAL ADVANCED SQUAMOUS CELL CARCINOMA OFTHE HEAD AND NECK (HNC). A PHASE II STUDY

*Ida Colantonio, *Elvio Russi, *Gianmauro Numico, *Riccardo Vigna-Taglianti,*Gianna Di Costanzo, Vigo V, Bacigalupo A, §Vitiello R, Benasso M, *Merlano M*S.Croce General Hospital-Cuneo-Italy; National Cancer Institute-Genoa-Italy;§SS Annunziata General Hospital-Savigliano-Italy

C-mab combined with radiotherapy was superior to radiotherapy alone in pts withHNC (Bonner 2006). Preliminary data of C-mab and chemo-radiation (Pfister 2006) ina similar pts’population, albeit encouraging, showed major toxicities, suggesting theneed for a less toxic scheduling. On the basis of a supposed lower toxicity,we thereforecombined rapidly alternating chemo-radiation and C-mab in HNC. Criteria foreligibility included: measurable, not previously treated, histological confirmed, stageIII/IV HNC (excluding nasopharynx), unresectable disease or surgery refusal.Treatment consisted of cisplatin 20mg/m2/day and 5Fu 200mg/m2/day, days 1-5, q.3wks, three times. Radiation, 2 Gy/day, 5 days/week, was given to fill up the pausesbetween the chemotherapy courses and after the last chemotherapy week, up to 70 Gy.In case of major response with (or suspicion of) persistent disease, salvage surgery wasconsidered. From 10/2005 to 04/2007 33 pts were enrolled: median age 57 (24-75);median ECOG P.S. 0 (0-1); Stage IV 82%; N1-3 91%; EGFR >80% cells = 51%; EGFR3+ = 82%. All pts were evaluated before treatment by a clinical staff includingcardiologist, nutritionist and dentist. Toxicity is evaluable on 24 pts (9 on-going).Grade 3-4 toxicities include febrile neutropenia (21%), diarrhea (16%),hypomagnesaemia (8%), mucositis (66%). A particular skin toxicity, starting asdesquamative moist dermatitis and confined at the irradiated field, occurred in 17/24(71%) pts, usually during the second part of the treatment. Perforation of colondiverticulus (1 pt), gastric perforation (1 pt), myocardial infarction (1 pt) and arterialthrombosis (1 pt) also occurred. 20 pts are evaluable for response at March 31 2007(intent to treat).

One pt died on treatment due to toxicity, major tumor responses were observed inall the remainings (14 CR + 5 PR). Three PRs were rendered disease free by salvagesurgery. At a maximum follow-up of 17 months, 18/20 pts are alive and 16/20 (80%)disease free.

D124* OSTEONECROSIS OF THE JAW (ONJ) IN CANCER PATIENTS(PTS) WITH BONE METASTASES TREATED WITH ZOLEDRONICACID: UPDATE ON PREVENTION

Roberto Vormola*, Cinzia Ortega*, Filippo Montemurro*, Roberto Faggiuolo,Rosa Anna Bucci*, Daniela Nanni, Franco Goia, Massimo Aglietta**University Division of Medical Oncology and Haematology Institute for CancerResearch and Treatment (IRCC), Candiolo, Italy

Introduction: ONJ is a serious complication of intravenous bisphosphonates,particularly zoledronic acid (Z). Published reports suggest that preventive dentistryprior to Z treatment may be the only effective approach in order to reduce the risk ofONJ onset.

Methods: At our Institute, from 3/2005, we predisposed a routine dental examination,panoramic radiograph and, where needed, tooth extractions for pts with risk factors forONJ before starting Z. During Z treatment we performed a follow-up consultationevery three and six months for patients with and without ONJ risk factors respectively.From 3/2005 to 3/2007 204 pts, median age 63 yrs (range 29-86) with bone metastasesfrom different cancers started the treatment with Z 4 mg i.v. every 3 or 4 weeks.Primary cancers were: 114 breast, 34 prostate, 19 multiple myeloma, 17 lung and20 others. 88/204 (43.1%) patients with suspected dental problems underwent carefuldental examinations and 30/88 were found to have one or more dental risk factors forONJ (7 caries, 4 granuloma, 11 parodontitis, 3 osteolisis, 1 mucosal ulcer, 4 prosthesisinjuries). They were cured and Z was started after a median of 2 months (range 1-6)from the procedure.

Results: A total of 2047 Z courses were administered. At a median number of Zadministration of 9 (range 2-28), 4/204 pts (1.96%) developed ONJ: 2 pts (1 breast;1 multiple myeloma) presented local risk factors for ONJ and performed dentalconsultation before Z; the other two pts (1 lung; 1 breast) without local risk factors,developed ONJ after 7 and 9 cycles of Z.

Conclusions: Preventive dentistry prior to Z treatment and patients’ educationabout a good oral hygiene seem to be effective: we found a decreased frequency ofONJ, in contrast with retrospective data. Oncologists must perform first visualinspection of oral cavity prior to Z therapy and, in presence of local risk factors,refer pts to dentists.

D125* THERAPEUTIC RECONSTITUTION OF LYMPHOPENICCANCER PATIENTS WITH EX-VIVO GENERATED AUTOLOGOUSTUMOR-REACTIVE T CELLS: EVALUATION OF FEASIBILITY ANDSAFETY IN SARCOMA PATIENTS

Daniela Montagna, Cinzia Tullio, Ilaria Turin, Simona Secondino, Enrica Montini,Roberta Schiavo, Enza Panzarella, Franco Locatelli, Salvatore Siena, RitaMaccario and Paolo PedrazzoliDipartimento di Scienze Pediatriche, Universita di Pavia, OncoematologiaPediatrica, Policlinico S. Matteo Pavia - Oncologia Medica Falck, OspedaleNiguarda Ca’ Granda Milano

Background: We previously demonstrated the feasibility of producing large-scaleamounts of anti-tumor cytotoxic T-cell (CTL) lines derived from peripheral bloodlymphocytes (PBLs) in compliance with GMP standards. We are currently evaluatingthe feasibility and safety of adoptive immunotherapy consisting of lymphoablativechemotherapy, to favour T cell proliferation in vivo, followed by CTL infusions forpatients with solid tumors.

Methods: Three patients with (metastatic) renal sarcoma, extraosseous PNET,endometrial stromal sarcoma, with large tumor masses progressing after failingconventional therapies, have been treated so far. In all subjects we were able to generateCTL lines displaying high levels of cytotoxic activity against patient tumor cells but notagainst non-malignant cells. Patients received lymphoablation with fludarabine/cyclophosphamide followed by CTL infusions, on day +14 and +28 and every 1-2months thereafter.

Results: Patient number 1 and number 2 received 6 CTL infusions. The mediannumber of CTLs administered/infusion was 206x106 (150-280) and 313x106 (120-600),respectively and disease progressed 6 and 5 months from the first CTL infusion. Patientnumber 3 so far received 12 infusions of higher doses of CTL (median 676x106, range100-1726) and remains in stable disease at >2 years after starting CTL therapy. Noadverse events related to CTL infusions occurred. Immunological monitoring,performed in two patients, showed an increased frequency of tumor-reactive cells inPBLs, persisting for 3-4 weeks after infusions.

Conclusions: We have shown that autologous ex vivo generated anti-tumor CTL linescan be infused safely, and are able to increase tumor-specific responses measured invitro. Optimisation of this immunotherapy strategy (frequency of lymphoablation andCTL infusion schedule) is currently under investigation.




ownloaded from


D126* SYNOVIAL SARCOMA: A RETROSPECTIVE ANALYSIS OF197 PATIENTS TREATED AT THE RIZZOLI INSTITUTE

Emanuela Palmerini1, Eric L. Staals2, Franco Bertoni3, Alesandra Longhi1,Massimo E. Abate1, Marilena Cesari1, Mario Mercuri2, Piero Picci4,Stefano Ferrari11Chemotherapy, 2 Orthopedics, 3 Pathology, 4 Research Lab of theMusculoskeletal Oncology Department, Istituto Ortopedico Rizzoli,Bologna, Italy

Background: The optimal treatment for synovial sarcoma (SS) is controversial. Thepresent study examines treatment and outcome of SS patients treated at a singleinstitution.

Methods: SS patients who underwent surgery at the Rizzoli Institute between 1976and 2006 were identified. Clinical charts and pathology reports were examined.

Results: The study included 197 patients (99 female and 98 male); median age was36 years (range 7-83); 152 (77%) had tumor located in the lower limb, 34 (17%) in theupper limb, 5 in the trunk (3%). Median maximum diameter was 6 cm (1-39) with54% of patients with lesions > 5 cm. 164 (83%) patients had localized disease and33 (17%) were metastatic at presentation. All localized patients underwent surgery,whereas 5 metastatic patients did not undergo surgical local treatment. 30 (16%)patients underwent amputation, the remaining had conservative surgery with adequatesurgical margins achieved in 89.5%. Radiotherapy was added in 46% of patients.Ifosfamide and/or doxorubicin-based chemotherapy was administered to 96 (50%)patients. With a median follow-up of 55 months (10-314), the 5-year overall survival(OS) was 65%: 11% for metastatic and 74% for localized patients. The 5-yeardisease-free survival (DFS) was 57% in localized patients. Age £ 18 (87% vs52%, p = 0.002), size < 5 cm (67% vs 43%, p = 0.002), biphasic histology (65% vs 48%,p = 0.03) and adequate surgical margins (59% vs 43%, p = 0.09) influenced the 5-yearDFS, whereas site, type of surgery and use of RxT or chemotherapy did not.

Conclusions: Patients with metastatic SS have a poor prognosis. In those with localizeddisease a good rate of cure can be achieved. Age, size, histology and surgical marginsinfluence prognosis, whereas the chemotherapy role has to be proven.

D127* IGF1 AND IGF2 AS PROGNOSTIC FACTORS IN GISTS

Chiara Braconi*, Raffaella Bracci*, Italo Bearzi, Francesca Bianchi*, SimonaSabato, Alessandra Mandolesi, Laura Belvederesi*, Riccardo Cellerino**Centro Regionale di Genetica Oncologica, Universita Politecnica delle Marche,Ancona, Anatomia ed Istologia patologica, Universita Politecnica delle Marche,Ancona

Background: Some evidence suggest the involvement of the IGF system in theevolution of GISTs.

Materials and methods: We studied the immunohistochemical expression of IGFR1,IGF1 and IGF2 in 94 samples of GISTs diagnosed between 1987 and 2006. IGF1 andIGF2 staining was scored in three classes: negative (N), moderate (M), strong (S)expression. A further classification was obtained considering IGF1 and IGF2 scorestogether, resulting in two classes (low L and high H). IGF1 and IGF2 protein expressionwas correlated with histopathologic characteristics (class of risk, histotype, site oftumor, mutational assessment) and disease free survival (DFS).

Results: Seventy-seven GISTs were radically resected, while 17 were metastatic atpresentation. IGFR1 was overexpressed in all cases. IGF1 and IGF2 expression wasabsent in 25 and 43 cases respectively, moderate in 27 and 12 cases and strong in 25 and22 cases. Strong expression of IGF1 significantly correlated with higher risk (p0.0002),metastatic (p0.0001) and relapsed (p0.08) GISTs. Strong IGF2 expression correlatedwith higher risk GISTs (p0.01), while absence of IGF2 expression correlated with nonrelapsed GISTs (p0.01) and PDGFRa mutated GISTs (p0.003). The H class wascorrelated with higher risk GISTs (p0.0001) and the L class correlated with a localpresentation of the disease (p0.01). The KaplanMeyer analysis (N vs M vs S and H vs L)showed a significant worsening of the DFS with the increase of IGF1 (p0.005), IGF2(p0.003) and IGF1-IGF2 (p0.005) expression. In the subgroup of patients withoperated high risk GISTs (35) there was a better trend in DFS for patients affected byGISTs with negative or moderate IGF1, IGF2.

Conclusion: IGF1 and IGF2 expression seems to correlate significantly with diseaseoutcome and might help clinical choices.

D128* THE IMPACT OF SEARCHING FOR BRCA1/2 LARGEGENOMIC REARRANGEMENT ON BRCAPRO CARRIER PREDICTION

1Carlo Capalbo, 1Amelia Buffone, 1Annarita Vestri, 2Enrico Ricevuto, 2Tina Sidoni,1Laura Ottini, 1Mario Falchetti, 1Enrico Cortesi, 3Paolo Marchetti, 4GiovanniScambia, 1Silverio Tomao, 5Christian Rinaldi, 1Massimo Zani, 1Sergio Ferraro,1,5Luigi Frati, 1Isabella Screpanti, 1,5Alberto Gulino and 1Giuseppe Giannini1Department of Experimental Medicine and Pathology, University La Sapienza,00161 Rome; 2Department of Experimental Medicine, University of L’Aquila,67010 L’Aquila; 3Medical Oncology, S. Andrea Hospital, Rome; 4Department ofOncology, Catholic University of the Sacred Heart, Campobasso; 5NeuromedInstitute, Pozzilli, Italy

Background and aims: Several models were developed to help genetic counsellors inselecting individuals with high probability of being BRCA1/2 mutation carriers.Among them BRCAPRO, BOADICEA and Myriad II proved to be useful tools inselecting possible BRCA1/2 mutations carriers. We have used and validated the ICsoftware, the Italian country-customized version of BRCAPRO developed by Marroniet al. Our experience suggest that an IC software carrier prediction ‡80% identifiesprobands with a genetic mutations responsible for the inherited breast/ovarian cancersyndrome observed in their family, independent of their genetic test result. Inparticular, we addressed the question of whether the apparent failures of the ICsoftware in probands with a carrier prediction ‡80% might be at least partiallyexplained by the occurrence of large genomic rearrangements in BRCA genes.

Patients and methods: We have screened our series, previously tested for deleteriouspoint mutations, searching for BRCA1 and BRCA2 genomic rearrangements. In brief,for each family we selected a breast and/or ovarian cancer-affected individual as theindex case (proband). The entire coding sequences and each intron/exon boundary ofBRCA1 and BRCA2 were screened by protein truncation test (PTT, limited to BRCA1exon 11) and/or direct sequencing. The 83 probands with no detectable BRCA1/2 pointmutations were further screened by Multiple Ligation Probe Amplification (MLPA).For each proband, the a priori probability of carrying a pathogenic BRCA1/2 germlinemutation was calculated by the IC software version 3.4. Index cases were classified as‘carrier-positive’ or ‘carrier-negative’ with a threshold of 10% mutation carrierprobability.

Results: Twenty-nine of the 112 probands tested for BRCA1/2 genes harboureda pathogenic germline point mutations. Two showed BRCA1 rearrangements involvingexons 18-19 in the first case and exons 23 and 24 in the second case. They accounted for2.4 % of the BRCA1/2 point mutation negative cases and for 1.8% of our total number.The molecular details of the BRCA1 exon 23-24 were characterized for the first time.No BRCA2 rearrangements were detected, suggesting that these rearrangements arerare out of the context of male breast cancer probands with breast cancer familialhistory. Application of the IC software to our serie confirmed its good performanceswith a high sensitivity (86%) and negative predictive value (89%). In particular, itallocated about 50% of the total 29 BRCA1/2 point mutations in the high-risk group(IC carrier probability ‡80%). Interestingly, in the moderate-risk group (IC carrierprobability ‡10% and <80%) only 12 out of 57 (21%) probands showed pointmutations positive while 72.2% of the probands assigned to high-risk group (IC carrierprobability ‡80%) were point mutation positive (p<0.0001). In addition by MLPAanalysis we showed that 2 out of 5 high-risk and point mutation negative probandsharboured BRCA1 large genomic rearrangements. This further raised the mutationfrequency in the IC carrier probability ‡80% group from 72.2% to 83.3%.

Conclusions: In conclusion, we provided evidence that breast/ovarian cancerfamilies with IC software carrier probability prediction ‡80% are indeed mutated onthe BRCA genes in more than 80% of the cases and that large genomic rearrangementswere found in more than 10% of these probands. Based on this we propose that all theprobands with a carrier probability prediction ‡80% determined by the BRCAPRO(and its Italian country customized version) have to be considered as carriers ofa strongly predisposing genetic alteration either in the BRCA1/2 genes or in other yetundescribed gene locations, independent of our ability to detect such mutations.

D129* RETROSPECTIVE ANALYSIS OF P-STAT6 EXPRESSION ASA PREDICTIVE MARKER IN PRIMARY NERVOUS SYSTEMLYMPHOMA PATIENTS ASSIGNED TO HIGH-DOSE METHOTREXATE

Giuseppe Altavilla, Vincenzo Pitini, Carmela Arrigo, Grazia Marabello, ClaudiaNaro, Chiara Tomasello, Mariacarmela SantarpiaHuman Pathology Dpt, Medical Oncology and Innovative Therapies Unit,University of Messina

Background: Recent immunohistochemical data and gene expression values obtainedby microarray analysis have demonstrated that a majority of Primary Nervous SystemLymphoma (PCNSL) express both bcl-6, a germinal center B-cell marker, as well asMUM-1, which is an activated B-cell marker, suggesting an overlapping histogenetictime slot of B-cell differentiation. In addition, an increased expression of activatedP-STAT6, which is a transcription factor primarily activated by IL-4, seems to predictearly progression and short survival in patients (pts.) treated with high-doseMethotrexate (HD-MTX)-based chemotherapy. To investigate the clinical impact ofthe P-STAT6 expression in this setting we have analyzed P-STAT6 expression inavailable tumor tissue blocks of 25 PCNSL pts. treated with HD-MTX who have hadfollow up for at least 2.5 years.

Methods: Immunohistochemistry for P-STAT6 was performed on deparaffinizedformalin-fixed tissue sections using an indirect immunoperoxidase method afterappropriate antigen Retrieval. Responses were evaluated according to the InternationalWorkshop criteria for PCNSL (JCO, 2005). Progression-free survival (PFS) and overallsurvival (OS) were calculated according to the Kaplan-Meier Method.

Results: 25 pts. (15 male, 10 female; mean age 52.1 years, range 37-61) were included inthe analysis. The immunohistochemical analysis showed three different patterns ofP-STAT6 expression: 7 pts. had absent P-STAT6 expression and low tumor cellulardensity (group A); 8 pts. had sparse positive P-STAT6 expression and low cellulardensity (group B), 10 pts. had strong P-STAT6 nuclear expression in tumor cells andon vascular endothelia and high cellular density (group C). The overall response ratesto treatment (CR+PR) were 83%for both group A and B compared to 5% of group C.Furthermore the pts. with intense P-STAT6 expression experienced an impressive early




Dow

nloaded from


progression (PFS median 2.5 months) and an OS very short (median 10 months). Todate pts. of groups A and B have not reached median OS and PFS.

Conclusions: PCNSL pts. with intense P-STAT6 expression experienced earlyprogression and short survival when treated with HD-MTX-based chemotherapy, sothe identification of new active drugs should receive high priority.

D130* THE DRAMATIC RESPONSE OF AESTHESIONEUROBLASTOMA CLINICAL CASE TO CHEMOTHERAPYWITH CISPLATIN AND ETOPOSIDE ALTERNATED TO DOXORUBICIN,IFOSFAMIDE AND VINCRISTINE COMBINATION

Viscomi C*, Mastroianni CM*, Turano S*, Biamonte R*, Ceniti S*, De Simone R*,Filice A*, Liguori V*, Manfredi C*, Rovito A* and Palazzo S*U.O.C Oncologia, P.O. Mariano Santo, Azienda Ospedaliera Cosenza

The esthesioneuroblastoma is a rare neuroendocrine cancer that derives from the nasalcavities olfactory cells. In the last twenty years have been described only 1000 cases andthe greater part of the recent data marks it a rate survival of the order of the 60-70% tofive years.

The most common symptoms are the nasal bleeding, nasal clogging and, in the localextended cases, signs/symptoms of intra-cranic hypertension (papilla edema, cefaleaand vomiting).

When is possible, the elective therapy is the surgery and radiotherapy. Thechemotherapy can be used in adiuvant/neoadiuvant attempt or also in a metastaticphase, even if its role is not still established with certainty.

Here we describe the case of a young man (38 years old) with locally extendedesthesioneuroblastoma.

He was been treated in a neurosurgery unit two months before to come in ouroncology’s unit with bilateral frontal craniotomy and cancer removal. A cerebral RMNafter the surgery demonstrated a residual disease in the nasal cavities and in the medialwall of the orbits that caused blindness and bilateral exophthalmos.

At the shelter we subjected the patient to octreoscan and total body computerizedtomography (CT) that confirmed the locally extended disease and the absence ofmetastases. We started a chemotherapy with cisplatin and etoposide alternated todoxorubicin, ifosfamide and vincristine combination with granulocyte colony-stimulating factor support after every cycle.

Already after the first chemotherapic cycle we observed an important reduction ofthe pain and a progressive decrement of the exophthalmos and vertigos.

Now, after eight cycles of chemotherapy, the CT demonstrates a subtotal diseaseremission; the pain is completely disappeared so as the bilateral exophthalmos . Stillpersist the blindness. For to optimize these results we have envoy the patient toa radiant treatment to obtaine a complete remission, to improve most possible thepatient quality of life and, if the good clinical response will be progressive, carry thepatient to the radicalization surgery.

D131* TEMOZOLOMIDE AND LOW-DOSE IRINOTECAN INRECURRENT OR PROGRESSIVE UNRESECTABLE MALIGNANTGLIOMAS

Claudia Caserta1, Sergio Bracarda1, Marta Rossi1, Alketa Hamzaj1, MarcoLupattelli2, Pietro Chiarini3, Paolo Giovenali4, Corrado Castrioto5, Lucio Crino1

1Medical Oncology Division, 2Radiation Oncology Division, 3Neuro-radiologyDivision, 4Pathology Division, 5Neuro-surgery Division; S.Maria dellaMisericordia Hospital, Perugia

Purpose: Recurrent high grade gliomas have a poor prognosis. Severalchemotherapeutic and targeted agents have been tested in this setting with responserates generally in the range of 0% to 21%. Irinotecan has shown activity againstrecurrent malignant glioma. This study was conducted to determine the antitumoractivity and safety of the irinotecan and temozolomide combination in patients withrecurrent or progressive unresectable malignant glioma.

Experimental design: We conducted an open label, non-comparative, dose-findingstudy. Patients with recurrent or progressive unresectable malignant glioma receivedtemozolomide at the dose of 150 mg/m2/day on days 1-5 plus irinotecan administeredas a 90-minutes intravenous infusion on days 1 and 15 of each 28-days cycle, fora maximum of six cycles. The irinotecan dose was escalated in successive cohorts ofthree patients from 90 mg/m2 to 180 mg/m2. The progression free survival at 6- and12-months, the objective response rate and safety of this chemotherapeutic regimenwere assessed.

Results: Twenty patients were enrolled into the study from February 2001 (4 with gradeIII glioma and 16 with grade IV glioma). Sixteen patients received previouschemotherapy. Eighteen patients were evaluable for response (two cases too early).Objective responses (partial responses) were observed in 6 of the 18 patients resultingin an intent-to-treat response rate of 27.8%. Five achieved stable disease (33.3%) andseven patients (38.9%) had progressive disease. The progression free survival at6-months was 47.1% and at 12-months was 17.6%. The toxicity of chemotherapeutictreatment was acceptable. The most common adverse events were: GPT/GOT increase(10% grade 2, 5% grade 3); neutropenia (5% grade 4, 5% grade 2); thrombocytopenia(5% grade 4), emesis (5% grade 2).

Conclusions: The combination of low dose of irinotecan with temozolomide is anactive and well tolerated regimen for recurrent high grade gliomas.

D132* TEMOZOLOMIDE (TMZ) CONCOMITANT TORADIOTHERAPY (RT) PLUS 12 CYCLES OF MAINTENANCECHEMOTHERAPY IN NEWLY DIAGNOSED GBM: EFFICACY PROFILE

Franceschi Enrico1, Tosoni Alicia1, Blatt Valeria2, Bartolini Stefania1, TalliniGiovanni3, Magrini Elisabetta3, Pession Annalisa3, Morandi Luca3, Ermani Mario4,Brandes Alba A 1

1 Medical Oncology Department, and 3 Pathology Department of Bellaria-Maggiore Hospital, Azienda –USL di Bologna; 2 Medical Oncology Department,Istituto Oncologico Veneto-IRCCS, Padova; 4 Statistic and Informatic Unit,Neurosciences Department, Padova University, Italy

Background: TMZ concomitant to RT followed by 6 cycles of maintenancechemotherapy improves median survival in newly diagnosed GBM. In the same groupof patients, MGMT promoter methylation status has been correlated to improvedsurvival and PFS. The aim of the present study was to assess the activity of TMZconcomitant to RT followed by 12 cycles of maintenance chemotherapy or up toa contrast enhanced MRS shows the presence of tumor. We also asses the correlationwith MGMT promoter methylation status.

Methods: Newly diagnosed histologically confirmed GBM patients were treatedwith TMZ (75 mg/m2/day) concomitant to RT (60 Gy/30F) followed by TMZ (150-200mg/m2 days 1-5,q28). MGMT methylation status was analyzed by methylation specificPCR.

Results: 104 consecutive patients (67 males), median age 53 (range 20-73), medianKPS 90 were enrolled with a median follow up of 16 months (range 4-62). Of these98.1% had a debulking surgery. Six patients (5.5%) discontinued chemotherapy fortoxicity, and 64 (58.2%) for disease progression. The median TTP was 11 months(CI95%: 8.5-13.5), and the median survival 23 months (CI95%: 15.6-30.3). MedianTTP and median survival were 29 months (CI95% 20.0-38.0) and 38 months (CI95%:20-56) respectively in methylated patients (32.7%) compared to 9 months (CI95%8.3 - 9.7) and 17 months (CI95%: 13-17) in unmethylated patients (67.3%) (p<0.0001both for TTP and MST).

Conclusions: A marked correlation between MGMT methylation status and clinicaloutcome has been shown in GBM patients treated with TMZ concomitant to RTfollowed by 12 cycles of maintenance chemotherapy. The continuation of maintenancechemotherapy up to a lesion was present in MRS results in positive outcome in terms ofsurvival. Further large studies would be required for more definitive conclusions onhow long the maintenance chemotherapy should be delivered.

D133* CLINICAL IMPLICATIONS OF IMMUNOHISTOCHEMICALASSESSMENT OF SOMATOSTATIN RECEPTORS SUBTYPE 2 AND5 IN THE DIAGNOSTIC AND THERAPEUTIC MANAGEMENT OFGASTRO-ENTERO-PANCREATIC NEUROENDOCRINE TUMOURS

Francesco Sclafani1, Carlo Carnaghi1, Luca Di Tommaso2, Arturo Chiti3, GiadaFranchi2, Lorenza Rimassa1, Maria Chiara Tronconi1, Massimo Roncalli2,Armando Santoro1

1Unita Operativa di Oncologia Medica e Ematologia, Istituto Clinico Humanitas,Rozzano (MI). 2Unita Operativa di Anatomia Patologica, Istituto ClinicoHumanitas, Rozzano (MI). 3Unita Operativa di Medicina Nucleare, Istituto ClinicoHumanitas, Rozzano (MI)

Background: Somatostatin analogues are useful in diagnosis and treatment ofpatients with gastro-entero-pancreatic neuroendocrine tumours (GEP NETs)expressing somatostatin receptors (SSTRs). Octreotide scintigraphy is routinely usedin GEP NETs staging, and represents the criterion of choice for a treatment withsomatostatin analogues. SSTRs expression can be also assessed byimmunohistochemistry (IHC) that is a reliable method to select patients suitable fora somatostatin analogues treatment and gives the opportunity to optimize thediagnostic indications of scintigraphy in a cost effectiveness perspective.

Methods: We retrospectively identified all patients with histopathological diagnosisof GEP NETs, attending our Institute from 1998 to 2006. Inclusion criteria requireddiagnosis of metastatic disease, availability of tumour specimens, and octreotidescintigraphy performed as staging procedure. A comparison between SSTRs expressiondetected by scintigraphy and IHC was performed.

Results: Twenty-seven patients were evaluated; 17 (63%) had a foregut carcinoid,7 (26%) a midgut carcinoid, 1 (4%) a hindgut carcinoid and 2 (7%) an unknownprimary site GEP NETs. SSTRs expression was detected in 17 patients (63%) byoctreotide scintigraphy and in 24 patients (89%) by IHC. The expression of SSTRsdocumented by scintigraphy was confirmed in all cases by IHC, on the other hand IHCrevealed SSTRs expression in 7 patients (26%) with a negative scintigraphy.

Conclusions: In our experience, we observed a low sensitivity of octreotidescintigraphy (71%), when compared with IHC. As main criterion for the feasibility ofbiotherapy, tumor uptake at octreotide scintigraphy could hence underestimate SSTRsexpression, cutting off patients who could benefit from a somatostatin analogues-based




ownloaded from


treatment. Encouraged by the evidences raised from this study, and by the immediacyand low cost of IHC, we designed a new diagnostic algorithm for GEP NETs, in whichthe use of octreotide scintigraphy is restricted to IHC positive patients suitable forsurgical or loco-regional procedures.

D134* A SINGLE-INSTITUTION EXPERIENCE: 105 CASES OFMERKEL CELL CARCINOMA

Emilio Bajetta, Laura Catena, Marco Platania, 1Mario Santinami, 1RobertoPatuzzo, Giuseppe Procopio, Sara De Dosso, Monika Ducceschi, Elena Verzoni,Milena VitaliMedical Oncology Unit; 1Surgery Unit of Melanoma-Sarcoma; FondazioneIRCCS "Istituto Nazionale dei Tumori, Milan – Italy

Background: Merkel cell carcinoma (MCC) is an uncommon skin cancer ofneuroendocrine origin that occurs usually in elderly population. The annual incidenceis about 0.01-0,23/100.000.

It is characterized by aggressive course with a high rate of relapse after resection ofthe primary localization. Up to date the optimal approach to the disease is poorlydefined.

Patients and methods: In our Institute, we collected 105 patients (pts) from 1985 toour days. Patients characteristics, tumor and treatment-related factors were analyzedfor their association with recurrence and overall survival.

The sex distribution was 56 females and 49 males; mean age at diagnosis was65.4 years (range 30-87).The primary tumour was located: 66 (63%) legs and arms,18 (17%) head and neck region, 17 (16%) unknown and 4 (4%) trunk.

Disease stage at presentation was: I 55 pts (52%), II 45 ( 43%), III 5 (5%).

Results: Surgery was the treatment of choice. Sentinel lymph-node biopsy (SLNB) wasperformed in 22 pts (21%) with stage I disease. Biopsy showed microscopic metastasesin 8 pts (7,6%) and they underwent to elective lymph node dissection (ELND).

ELND was the first treatment also for 40 pts with stage II disease.No adjuvant radiotherapy and chemotherapy was performed. Chemotherapy with

platinum compound and etoposide was performed only in metastatic disease (5% ofpts).

Five-year survival was 58% and no correlation with age and site of primary wasobserved. In our series the 5-years survival was related to sex (female 69%, male 46%p .0097) and stage (stage I 68%, stage II 51% p.0419). Data about TTP were comparedwith historical controls and will be presented during the meeting.

Conclusions: In our observation, surgery represents the first-line treatment and theonly potentially curative approach.

SLNB is a useful staging procedure in MCC and seems to be a good option toavoid limphoadenectomy. The role of ELND as curative approach needs to be betterdefined through prospective clinical trials. Also the role of chemotherapy and/orradiotherapy needs to be better understood.

Authors thank data management by scientific service I.T.M.O.

D135* THE IMPACT OF SURGERY ON METASTATIC MELANOMA

1Veronica Parolin, 1Rolando Nortilli, 1Carla Strina, 1Elena Fiorio, 1Renata Sabbioni,1Teodoro Sava, 1Gian Luigi Cetto1Department of Clinical and Experimental Medicine, University of Verona, Italy

Background: Patients with metastatic melanoma have traditionally been managed withvarious systemic treatments; however the overall prognosis remains poor. Surgicaltherapy plays an important role in the management of selected patients with advanceddisease. The purpose of this study is to evaluate retrospectively the experience ofsurgical resection of metastatic lesions and the impact on survival.

Methods: We reviewed the data of 452 patients with cutaneous melanoma followedat our institute between 1987 and 2006. Survival probability was determined byKaplan-Meier estimates, using a log-rank analysis to determine significant differencesand a logistic regression model to assess correlations.

Results: The patients who developed distant metastasis were 188 (41.6%), with averageage of 54 years at diagnosis (range 18-82). The median survival time was 9 months.Thirty-two patients underwent surgical resection of distant tumor, alone or incombination with other treatments, with a median survival time significantly superiorcompared with patients not surgically treated (p<0.0001, HR=0.3333, 95% CI =0.2822to 0.5840). Of all patients with stage IV melanoma, there were 39 patients (20.7%) withprolonged survival of 2 years or longer and 17 of them (43.5%) underwentmetastasectomy. The 2-year, 5-year and 10-year survival rates were 16.5%, 2.6%,and 1.6%, respectively. As evaluated by logistic regression, of all the modalities oftherapy given, only surgery correlated with prolonged survival (p<0.0001). The currentstudy failed to show that systemic chemotherapy alone significantly influencedsurvival, but the combination of surgery and chemotherapy resulted in the longestmedian survival time (192 months).

Conclusions: The current study demonstrates that of the modalities of therapy given,only surgery significantly influences survival. We conclude that metastasectomy, inpresence of a limited number of lesions, a long relapse-free interval and residualdisease, is correlated with long-term outcome and offers the best chance for prolongedsurvival.

D136* IN VITRO AND IN VIVO ACTIVITY OF VALPROIC ACID INMYELOMA

Neri P1,2,3, Calimeri T1, Propato M1, Rossi M1, Pietragalla A1, Ventura M1,Cucinotto I1, Bulotta A1, Eramo O1, Di Martino MT11, Munshi NC2,3, AndersonKC2, Tagliaferri P 1 and Tassone P1,2,3

1Medical Oncology Unit, University of ‘‘Magna Græcia’’, Campus S. Venuta,Catanzaro 88100, Italy, 2Jerome Lipper Multiple Myeloma Center, Dana-FarberCancer Institute and 3VA Boston Healthcare System, Harvard Medical School,Boston, MA 02115

Valproic acid (VPA) is a well-tolerated anticonvulsant that has been recentlyidentified as a histone deacetylase (HDCA) inhibitor. VPA induces hyperacetylationof histone H3 and H4 and inhibits both class I and II HDCACs. It has been recentlyshown that VPA exerts in vitro and in vivo anti-tumor activity against solid tumorsand some leukemias. The aim of this study was to evaluate the in vitro and in vivo effectsof VPA on multiple myeloma (MM) cells. By MTT assay, we evaluated the in vitroactivity of VPA on IL-6 independent (MM1s, OPM1, DOX-40) and dependent(INA-6) MM cell-lines. Induction of acetylation was assessed by Western Blot analysis.In vivo effects were studied using a xenograft animal model of human MM. A cohort ofSCID mice bearing subcutaneous MM1s were treated i.p. daily with VPA (200 mg/kg,n=5) or vehicle alone (n=5) for 16 days. Tumors were measured every 2 days, andsurvival was calculated using the Kaplan Mayer curve.We first demonstrated thein vitro activity of VPA against IL-6 independent and dependent MM cells. A time- anddose-dependent decrease of cell growth and survival of MM cell-lines was observed,with IC50 in the range of 1-3 mM. A preliminary Western Blot analysis of MM1scells exposed to VPA showed an accumulation of acetylated histones in treated cellsversus untreated controls. We next evaluated the in vivo activity of VPA in a xenograftMM model. We found a significant (p=0.006) inhibition of tumor growth in micetreated with VPA compared to control which translated into a significant (p= 0.002)survival advantage in the VPA treated animals versus the control group. Effects inducedin vivo by VPA on cell cycle and global gene expression, by DNA microarray profiling,are presently under investigation.Taken together, our data demonstrate the in vitroand in vivo anti-tumor activity of VPA and provide a preclinical rationale for its clinicalevaluation, both as a single agent and in combination, to improve patient outcomein MM.

D137* WEEKLY LOW-DOSE PACLITAXEL AND CARBOPLATINTREATMENT VERSUS STANDARD THERAPY IN LATE RECURRENTOVARIAN CANCER PATIENTS

GP. Lupi, L. Agoni, L. Carrara, R. Franzini, A. Gorio, A. Gambino, E. Sartori,S. PecorelliUniversita degli Studi – Dipartimento di Ginecologia Oncologica - Brescia

Objective: Patients with advanced ovarian cancer who achieve a complete responsehave a high risk of recurrence. The combination of Paclitaxel and Carboplatinchemotherapy in a 3 weeks schedule (MDD) for patients with late recurrences isconsidered as an effective regimen, but poor efficacy in terms of PFS, OS and thetoxicity move trought other optional therapy. The aim of this study was to comparedlow dose metronomics regimen (LDM ) with the standard therapy (MDD) to evaluatethe potential benefice in terms of PFS, OS and Toxicity related.

Methods: Between 01/1999 and 05/2004 30 pre-treated patients platinum-sensitive(time to progression after 1st line therapy >12 months) were enrolled (median age: 60,range 41-77). All patients were in pathological complete response after the firsttreatment. 20 relapses were retreated with standard schedule (MDD: Paclitaxel 175 mg/mq d1 and Carboplatinum AUC6 d1, q21 ) and 10 with methronomic schedule (LDM:Paclitaxel 60 mg/mq and Carboplatinum AUC2 using 3 weekly courses with a 1-weekbreak schedule).

Results: The overall response rate (CR and PR) was 80.95% vs 71.43% for MDR vsLDM (P>0.05). The complete responses were 57,14% and 42,86% respectively(P>0.05). Serological responses were 66,67% (MDD) vs 50% (LDM); macroscopicalresponses were 57,14% and 50% respectively. In LDM group no patients had G2 orhigher thrombocytopenia, 29% of patients developed neurotoxicity G3, while theworste toxicity in MDD group was vomiting. Although the limited number of cases ourdata showed that MDD has a better PFS (13 vs 9 month ), OS and safety profile.However this trend is not statisticaly significative (P>0.05).

Conclusion: Weekly Paclitaxel/Carboplatinum infusion therapy for recurrentovarian cancer could be considered as an optional regimen. LDM combination, asused in our study, doesn’t produce better response rate compared with MDD. Thetoxicity profile is acceptable. Even if the LDM regime results safety, the appropriateddoses aren’t still defined.

D138* CORRELATION BETWEEN FDG –PET EVALUATION ANDPATHOLOGICAL RESPONSE TO NEOADJUVANT CHEMOTHERAPYIN ADVANCED EPITHELIAL OVARIAN CANCER PATIENTS: FINDINGSFROM THE ARIANNA 02 PROJECT

Marta Rosati, Claudio Zamagni, Alessandra Musto, Alessandra Bernardi, SaraQuercia, Federica Rosati, Nicoletta Cacciari, Mass ari Francesco, Pierandrea DeIaco, Stefano Fanti and Andrea Angelo Martoni




Dow

nloaded from


Unit of Medical Oncology S.Orsola-Malpighi Hospital, Nuclear Medicine Unitand Dept. of Obstetrics and Gynecology University of Bologna Bologna – Italy

Background: primary chemotherapy in ovarian cancer allows to evaluate the efficacy ofanticancer therapy in a relatively short period of time. Pathological complete response(absence of residual cancer cells at surgery) significantly correlates with a survivaladvantage. The primary aim of this study is to investigate the correlation between 18FFDG PET evaluation and pathological response in advanced epithelial ovarian cancerpts treated with primary carboplatin-paclitaxel chemotherapy.

Patients and methods: stage IIIb-IV hystologically confirmed ovarian cancer pts notsuitable for optimal debulking surgery and candidates for primary chemotherapy wereeligible. Patients underwent diagnostic laparoscopy at baseline and were evaluated atbaseline, every 3 courses and at the end of primary chemotherapy (before surgery) withPET scan. In the first 11 pts PET scan was carried out before each cycle. Metabolictherapy response was quantitatively measured by SUV max and by relative (%) SUVmax decrease. Standard diagnostic procedures (abdominal CT scan, transvaginalechography, CA 125) were also applied. Pathological response was evaluated accordingto a 5 grade-scale, ranging from grade 1 (no response) to grade 4-5 (only small clustersor individual cells residual, or no malignant cells at all).

Results: Up to now 36 pts have been enrolled and 9 of them are still on chemotherapy.The present analysis is focused on the first 27 pts: median age 66 (range 43-77), medianKPS 90% (70-100); stage IIIb: 1 pt (4%); stage IIIC: 13 pts (48%); stage IV: 13 pts(48%). Twenty-five pts received carboplatin AUC5 plus paclitaxel 175 mg/m2, while2 elderly pts were treated with carboplatin AUC5 single agent. After a median numberof 6 cycles (range 5-7) we observed 17 (63%) grade 4-5 pathological responses. BaselinePET SUVmax was pathological (focal lesions with SUVmax >2, median 10, range 3-23)in all pts; a complete normalization (SUVmax <2) was observed in 18/27 cases (67%)and the overall concordance between PET and pathological evaluation after 6 coursesof primary chemotherapy was 81% (22/27). A decrease ‡ 50% in SUVmax after thethird cycle has a 89% concordance with pathological response and none of the 7 ptswithout such a SUVmax decrease obtained a grade 4-5 pathological response (p .003).

Conclusion: the correlation between FDG-PET response and grade 4-5 pathologicalremission is 81% (95% CI: 67-96%). A decrease of SUVmax ‡ 50% after the thridcycle of chemotherapy is significantly more frequent in grade 4-5 pathologicresponders.

D139* COMBINATION OF NON-CYTOTOXIC AGENTS WITHANTI-ANGIOGENIC ACTIVITY FOR METRONOMIC THERAPY OFSOLID TUMORS: ANTITUMOR ACTIVITY AND BIOLOGICAL EFFECTS

Cristina Noberasco1, Gianluca Spitaleri1, Patrizia Mancuso2, Alessandra Milani1,Andrea Rocca3, Francesco Bertolini2, Giuseppe Curigliano1, Tommaso de Pas1,Sabrina Boselli1 and Filippo de Braud1

1Clinical Pharmacology and New Drugs Development Unit; 2Division ofHematology-Oncology; 3Division of Medical Oncology; Department of MedicineEuropean Institute of Oncology, Milan, Italy

Successful cancer therapies targeting tumor vasculature would be expected to block theexisting blood supply and to prevent tumor neovascularization. In this study we testedthe combination of 3 distinct drugs with proved antiangiogenic properties: a-interferon (IFNa), thalidomide (T) and celecoxib (C) administered in two or threedrugs combinations.Patients with metastatic solid tumors with slow growth rate(defined as free interval from treatment > of 6 months or disease increase < 50% in thelast 2 months) were randomized in Groups A 1, A2, B1, B2, C1, C2, receiving two drugscombinations. After 2 months of treatment the groups A2, B2, C2 add the third drug.Treatment plan included daily administration of IFNa 0.5 MU/12 hrs sc,T 100 mg/12hrs po, C 200 mg/12 hrs po for at least 4 months. Circulating endothelial cells (CEC)were measured by flow cytometry before therapy and every two months. From January2002 to Sept 2005 we randomized 62 patients, with good performance status. The mostcommon tumors were clear cell renal carcinoma (19 patients) and hepatocellularcarcinoma (19 patients). Sixty-one patients were evaluable for toxicity and 58 pts foractivity. We recorded 3 partial response (PR 5%) and 40 stable disease (SD 69%).Median duration of response in responding patient (PR+ SD >4 months ) was 11.31months; the progression free > 6 months ratio was 30%. Only 1 patient developeda liver grade IV toxicity; grade III adverse events included leucopenia(3%);transaminitis (8%);because of the incidence of lethargy (10%) the dosethalidomide was reduced to 100mg. In 29 pts there was a statistical significance in CEClevels during the first two months (18 patients with SD > 6 months). Metronomic, longterm administration of IFNa + Celecoxib + Thalidomide is feasible. The triplet scheduledid not add any advantage respect with double combination. Even if don’t seem toimpact with survival benefit. CEC could be considered as surrogate marker ofantiangiogenic activity.

D140* ASESSMENT OF THROMBOTIC RISK IN CANCER PATIENTS:PROPOSAL OF A SCORING SYSTEM. A MONOCENTRIC STUDY

Giulio Giordano1, Giuliana Farina1, Rosa Tambaro1, Monica Specchia1, StefanoPapini1, Marisa Piunno1, Carla Antonelli1, Bruno Zappacosta1, Sergio Storti1, S.Pignata2

1Centro di Ricerca e Formazione ad Alta Tecnologia nelle Scienze Biomediche‘‘Giovanni Paolo II’’, UCSC, Campobasso, Italy, 2Istituto tumori di Napoli‘‘Fondazione G. Pascale’’

Background: Deep venous thrombosis (DVT) is present in about 3-15% of cancerpatient. Antithrombotic prophylaxis frequently is not oriented to real thrombotic orhaemorragic risk of patient.

Aims: To define the real thrombotic risk in neoplastic patient. We consideredcomplement fraction C3 and C4 and immune circulating complex (ICC) because theyactivate macrophage and platelets and increase tissue factor level. We recognize alsototal cholesterol (TC) and triglycerides level (TL), because linked with factor VIIactivation.

Methods: We evaluated 119 patients with solid neoplasm (62colon, 27lung, 18gastric,12 others) without anticoagulant prophilaxis. Of these only 102 were evaluable. Medianage was 68.5 years (R 57-83). M/F ratio was 72/47. The threshold value of third quartilewas chosen as risk cut-off (C3: 130mg/dl; C4: 32mg/dl; ICC: 2.9 mcg/ml; TC: 205mg/dl;TL:123mg/dl). We elaborate a scoring system in which 1 point was attributed to eachvalue inferior to third quartile.

Results: 19 patients (16%) showed DVT. Of these 14(74%) had a score £3 and 5 34. 83patients (81%) did not show DVT. Of these 50(60%) had a score 34 and 26 £3. Yatescorrected chi square test is 5.86 (p 0.015), with an OR of 4.2 (95%CI 1.4-12.3) and a RRof 3.2 (95%CI 1.3-8.3). Negative predictive value is 0.91 (95%CI 0.83-0.96) andpositive predictive value is 0.30 (95%CI 0.21-0.35). Sensitivity was 0.73 (95%CI 0.53-0.87) and specificity was 0.60 (95%CI 0.55-0.63).

Conclusions: Our scoring system is useful in distinguishing cancer patient with lowthrombotic risk and consent to avoid antithrombotic prophylaxis in patient withhigher bleeding and lower thombotic risk. Nevertheless these data need confirmationon a larger cohort of patients.

D141* OFF-LABEL PRESCRIPTION OF ANTINEOPLASTIC DRUGS:A PROSPECTIVE, OBSERVATIONAL, MULTICENTER SURVEY

Fausto Roila1, Enzo Ballatori2, Roberto Labianca3, Filippo De Braud4, KarenBorgonovo5, Olga Martelli6, Ciro Gallo7 and Francesco Perrone8, on behalf of theItalian Medical Oncology Association (A.I.O.M.)1Dpt. of Medical Oncology Perugia, 2Dpt. of Internal Medicine L’Aquila, 3Dpt. ofMedical Oncology Bergamo, 4European Institute of Oncology, Milan, 5Dpt. ofOncology, Fatebenefratelli Hospital, Milan, 6Dpt. of Oncology, S.GiovanniHospital, Rome, 72nd University of Naples, 8National Cancer Institute, Naples

An appropriate use of antineoplastic drugs, essential to obtain the results achievedin the clinical trials, should follow the registered indications and the approved doses.In oncology can happen that the drugs are prescribed off-label for different reasons.The A.I.O.M. carried out a study to verify the incidence and characteristics of theoff-label prescriptions. All patients (pts) submitted to chemotherapy in 18 oncologicalcenters were evaluated for two randomized non-consecutive days of 2 identified weekson May 2006. The study enrolled 644 pts. The analysis was done according to the typeof drug and the chemotherapeutic scheme. Considering the type of drug, 202/1053(19.2%) prescriptions were off-label. In 92/202 patients (45.5%) the drugs were used ina neoplasia for which was not approved but there was scientific evidences justifying theprescription (i.e., fluorouracil in esophageal cancer, cisplatin in gastric cancer,paclitaxel in endometrial cancer and carboplatin in non-small cell lung and bladdercancer). In 30/14 pts (14.8%/6.9%) the drugs were used in lines of chemotherapysubsequent/previous to that approved (i.e, capecitabine as second line in colorectalcancer/as first line in breast cancer). In 27 pts (13.4%) the drugs were prescribed fora rare neoplasia (i.e., fluorouracil in anal cancer, cisplatin and gemcitabine inmesothelioma and biliary tree cancer). Finally in 20/19 pts (9.9%/9.4%) for use inassociation/alone not approved (i.e., capecitabine in colorectal cancer/gemcitabine inbreast and ovarian cancer). The prescription of 172/398 schemes (43.2%) was off-label(246 pts received a single drug). In 92 pts (53.5%) one or more drugs of thecombination were not approved and in 54 (31.4%) the drugs were approved but not inthe combination used. In conclusion, off-label use of the antineoplastic drugsrepresents less than 20% of the prescriptions and most of these have scientific evidenceof efficacy.

D142* RANDOMIZED TRIAL OF INTRAVENOUS IRONSUPPLEMENTATION IN PATIENTS WITH CHEMOTHERAPY-RELATED ANEMIA WITHOUT IRON DEFICIENCY TREATED WITHDARBEPOETIN ALFA

Salvatore Siena, Antonio Farris, Salvatore Del Prete, Filomena Del Gaizo, DarisFerrari, Clara Bianchessi, Giuseppe Colucci, Francesco Di Costanzo, RobertoLabianca, Simona Secondino, Antonio Del Santo, Paolo PedrazzoliOncologia Medica Falck, Ospedale Niguarda Ca’ Granda

Background: Unresponsiveness to erythropoietic agents, occurring in 30-50% ofpatients, is a major limitation of treatment of chemotherapy-related anemia. We haveprospectively evaluated whether intravenous iron can increase the proportion ofpatients with chemotherapy-related anemia responding to darbepoetin alpha.




ownloaded from


Patients and methods: Between December, 2004 and February 2006, 149 patients withlung, gynaecologic, breast, and colorectal cancers and ‡12 weeks of plannedchemotherapy were enrolled from 33 Institutions. Patients were required to havehemoglobin 11 g/L and no absolute or functional iron deficiency. All patients receiveddarbepoetin 150 mcg subcutaneously once weekly for 12 weeks and were randomlyassigned to sodium ferric gluconate 125 mg IV weekly for the first 6 weeks (n=73) or noiron (n=76). Primary endpoint of the study was the percentage of patients achievinghemoglobin response (‡12 g/dL or 2 g/dL increase).

Results: Hemoglobin response by intention-to-treat analysis was 76.7% (CI: 65.4%-85.8%) in the darbepoetin/iron group and 61.8% (CI: 50.0%-72.7%) in thedarbepoetin only group (p=0.049). Among patients fulfilling eligibility criteria andhaving received at least 4 darbepoetin administrations, hemoglobin responses in thedarbepoetin/iron group (n=53) and in the darbepoetin only group (n=50) were 92.5%(90% CI: 81.8%-97.9%) and 70% (CI: 55.4%-82.1%), respectively (p=0.0033). Increaseof hemoglobin during treatment period showed a time profile favouring darbepoetin/iron with significant effect from week 5 on. The safety profile was comparable in thetwo arms.

Conclusion: In patients with chemotherapy-related anemia and normal iron status, IViron supplementation significantly reduces treatment failures to darbepoetin withoutadditional toxicity.

The study was funded by Dompe Biotec

D143* APPROACH OF ITALIAN ONCOLOGISTS TOWARD CARE OFADVANCED PATIENTS. A PILOT STUDY

Sandro Barni, Enrico Aitini, Giuseppe Colucci, Enrico Cortesi, Cesare Gridelli,Carmelo Iacono, Vito Lorusso, Marco Maltoni, Bruno Massidda, Paolo Pronzato,Riccardo Torta*, Guido Tuveri, Lucia SimonisMedical Oncology Treviglio, Mantova, Bari, Roma, Avellino, Ragusa, Lecce,ForlI, Cagliari, Genova, Trieste.*Clinical Psychology Torino. Medidata, Modena.

Discussing end-of-life issues is of great importance for advanced patients (AP) andtheir families, and a challenging topic for both the medical profession, patients andcaregivers. There is a scarcity of research literature to guide clinical practice.

The approach of Italian oncologists towards the care of AP is described, focusing onend-of-life care.

During 10 CME meetings concerning palliative care (PC) – Suffering Is Over (SIO)Project, held between March and November 2006, 238 oncologists filled ina questionnaire, which was adapted from Cherny and Catane (Cancer 2003), regardingtheir attitudes towards PC. Some questions specifically investigated end-of-lifeproblems.

The 238 oncologists completing the questionnaire were: male/female 56/44%, meanage 45.03 (+/- 8.95) and mean years of experience in Oncology 16.19 (+/- 9.33). Themajority (76%) were working in public or university hospitals. Oncologists were often(62%) or occasionally (28%) responsible for care of AP. 24% had never been involvedin coordinating encounters with the family of dying patients. 29% oncologists did not

make decisions regarding the admittance of AP to a hospice. 32% oncologists wereasked by AP to aid assisted suicide (90% of whom occasionally).

Caring for AP and dying patients depressed 21% doctors, and 19% felt emotionallyburnt out by dealing with too many deaths. One-third had to deal with the PC of onlynon-terminal patients.

Interviewed oncologists considered management of symptoms to be of primeimportance. The request for elective death remains to be infrequent in Italy.

SIO project is supported by an unrestricted grant by Grunenthal Italia.

D144* ANTIEMETIC PROPHYLAXIS WITH PALONOSETRONAPREPITANT AND DEXAMETHASONE IN PATIENTS WITHSARCOMAS TREATED WITH A THREE DAYS SCHEDULE OFEPIRUBICIN AND IFOSFAMIDE CHEMOTHERAPY

Giuseppe Badalamenti, Fabio Fulfaro, Lorena Incorvaia, Chiara Intrivici,Milena Sanfilippo, Carla Signorelli, Simona Macaluso, Giuseppa Maltese,Tommaso Pizzo, Antonio Russo, Nicola GebbiaDepartment of Oncology, Universita degli Studi di Palermo, Palermo, Italy

Multinational Association of Supportive Care in Cancer (MASCC) guidelines indicatethe association of 5HT3 antagonist, dexamethasone and aprepitant as gold standard forcontrol of acute emesis in patients who undergo to highly emetogenic chemotherapy.Aprepitant is a NK antagonist which showed an important activity in the control ofemesis in highly emetogenic chemotherapy. Palonosetron is a new 5HT3 antagonistthat seems to have a prolonged duration of action and good efficacy. Aim of this studyis to evaluate the activity and safety of a single dose of Palonosetron 0.25 mg iv inassociation with dexamethasone and aprepitant in patients with sarcoma who receivedhighly emetogenic chemotherapy consisting of Epirubicin 35 mg/sm day 1-2-3 andIfosfamide 3000 mg/sm day 1-2-3. Nausea and Vomiting were evaluated separately ina daily sheet compiled by the patients. Quality of life was measured by a specificquestionnaire.Patients and methods: Nine patients were enrolled in the study, 8 female, 1 male,median age 45 years (range 29-65). All the patients received the following schedule ofantiemetic prophylaxis: Day 1: Aprepitant 125 mg per os, palonosetron 0.25 mgiv,dexamethasone 16 mg iv. Day 2 and Day 3: Aprepitant 80 mg per os, dexamethasone12 mg iv. To control delayed emesis Dexamethasone was used 8 mg per os for Day 4-5and 4 mg per os for Day 6-7. Metoclopramide 10 mg im or iv could be used ondemand.

Results: 27 cycles of chemotherapy were administered.7/9 patients did not experiencevomiting and 3/9 patients did not complain nausea during chemotherapy. Strongnausea was present in only 1 case in the first and second cycle of chemotherapy and innone in the third cycle. Quality of life worsened in only 2/9 patients and rescue therapywas administered in only 3/9 cases.

Conclusion: From this preliminary results anti emetic profilaxis with palonoetron,aprepitant and dexamethasone was feasible and active in patients with sarcomas whoreceived three days schedule of ifosfamide and epirubicin chemotherapy.




Dow

nloaded from


Documents

session D: miscellanea