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110 Chemotherapy In vitro chemical eradication of small cell lung cancer: Application in autologous bone marrow transplantation. Benard J, Bettan-Renaud L, Gavoille A, Pica J-L, Beaujean F, Lopez M, RiouG.Laboraroire&PharmncologieCliniqueetMoleculaire.InsN’tu~ Gustave Rowsy, 94800 Villejuif. Em J Cancer Clin Oncol 1988;24:1561-6. Autologous bone marrow transplantation raises the question of the possible reinjection of tumour cells together with marrow. This paper investigates the ability of chemical compounds other than cyclo- phosphamide derivatives to eradicate small cell lung cancer (SCLC) in bone marrow. The responsiveness of SCLC lines to &-platinum, doxornbicin, VP16, Celiptiuma (an ellipticine derivative), Ditercalini- urna, a new drug belonging to the pyridocarbazole series, and Asta ZR were measured in agar-agar clonogenic assay. Cis-platinum and Diter- caliniun+’ exhibited a high tumouricidal effect. The low cloning efti- ciencies of SCLC lines in an agar-agar clonogenic assay did not allow turnout cells to be detected among bone marrow cells with sufficient sensitivity. Therefore cis-platinum and Ditercaliniuma were tested on bonemarrow-tumourcellmixturesculturedinaliquidmediumallowing the detection of one tumour cell par lad bone marrow cells. As cis- platinum exhibited a low myelotoxicity, it is proposed for purging bone marrows of patients with SCLC. Results of palliative chemotherapy for advanced small cell bron- chial carcinoma. Ftitze D, Harjung H, Katz R, Kober B. Medizinische Klinik V, Stadtis- cheKliniken.6100Darmsfodt. DtschMedWochenschr1988;113:1663- 8. Results of chemotherapy for small cell bronchial carcinoma were analyscxl retrospectively on 36 of 40 consecutive patients with the disease, admitted to an oncology unit between January 1985 and December 1987. The survival curves indicated a highly significant trend (logrankp=O.COl).Patients withextensivediseaseandKarnofskyindex of 40-50% had a median survival of four months, but for those with Kamofsky index > 50% it was 15 months. There was virtually no age difference between the two groups, but there were signilicant differ- ences regarding additional diseases (e.g. coronary heart disase, arterio- sclerosis,etc.),frcquencyofliverandCNS metastasesratesofcomplete or partial remission, number of early deaths, haematological toxicity, and severe weight loss (> 5 kg). These results suggest that aggressive chemotherapy (primarily designed for patients with limited disease) failed toimpmve thegraveprognosisofpatients with distant metastases and a low Karnofsky index (< 50%). Supportive care should be intensified for these patients. Phase II trial of oral Idaruhicin in advanced non-small cell lung cancer (NSCLC). Ardizr.oniA,PmnzatoP,RepettoL, DePalmaM,CanobbioL,Gulisano M, Fusco V, Rosso R, Ganzina F. lstituto Nazionale per la Ricerca sul Concro, 16132 Geneva. Cancer Invest 1988;6:409-11. The antitumoral activity and toxicity of a new daunorubicin analog (4-demethoxydaunorubicin, IMI 30, Idambicin) was tested in 20 con- secutivepatientswithnon-smallcelllungcancermosdypreu~tedwith chemotherapy. The drug was administered orally at a dose of 15 ms/m* for three days every 3-l weeks. Them were no clinical responses. Hematological and nonhematogical toxicities were mild. Unexpected high toxicity in a phase II study of teniposide (VM-26) in elderly patients with untreated small cell lung cancer (SCLC). Cerny T, Pedrazzini A, Joss RA, Brunner KW. fnstitutfw Medirinische Onkologie der Universital Bern, Inselspital. CH-3010 Bern. Em J Cancer Clin Oncol1988;24:17914. Teniposide (VM 26) as a single agent has shown promising results in the treatment of patients with small cell lung cancer. We treated 32 (30 evaluable) non-pretreated elderly and poor prognosis patients with small cell lung cancer with teniposide 100 m&lay (30 min infusion) days l-5, every 3-4 weeks. Overall initial performance status was poor (WHO 2 or 3 in 62%). Extensive disease (ED) was documented in 50% including five patients with CNS metastases all of whom received simultaneous cranial irradiation. There was an unexpected high early death rate of 30% (9/30) including Eve patients with early toxic death due to severe bone marrow suppression leading to fatal septicaemia. The overall response rate was only 33% with no complete response. Where appropriate non-responding or relapsing patients received second line treatment with multidrug regimens *radiotherapy. The overall median survival was 5.6 months [ED: 1.7, limited disease (LD): 7.5 months]. Median response duration was 5.4 months (ED: 5.1, LD: 6.7 months). For responding patients median survival was 8.8 months (ED) and 11.5 months (LD). We conclude that in elderly and poor performance status patients singleagentteniposideas usedin thisstudy hasan unacceptable high early death rate and that the response rate is inferior to modem standard multidrug regimens. Etoposide and split-dose cisplatin in bronchogenic carcinoma. LauerRC,FisherWB,PenningtonK,AnsariR,EinhomLH,LoehrerPJ. Department of Medicine, Indiana University. Indianapolis. IN 46223. Am J Clin Gncol. Cancer Clin Trials 1988;11:634-5. The Hoosier Oncology Group (HOG) treated 13 patients with bron- chogenic carcinomaandan innovative schedule of cisplatin and VP-16. Unexpected toxicity was noted, and live deaths secondary to granulo- cytopenia and septic shock and three episodes of renal failure. Despite earlyclosureofLhisstudy,weconcludethatthisscheduleofcisplatinand VP-16 results in greater toxicity than comparable dosages in a more mutine schedule. Randomized Phase II evaluation of iproplatin (CHIP) and carbo- platin (CBDCA) in lung cancer. A Southeastern Cancer Study Group trial. Kramer BS, Birch R, Greco A, Prestridge K, DeSimone P, Gmura G. University of Florida, Gainesville, FL. Am J Clin Oncol, Cancer Clin Trials 1988;11:643-5. Cisplatin-containing regimens have shown activity in both small and non-smallcelllungcancer. WethereforeconductedarandomisedPhase II trial of the new platinum congeners iproplatin and carboplatin in bmnchogenic carcinoma. The overall response rate in chemothempy- naive non-small cell patients with iproplatin was 3/48 (6%; 95% confidence interval 2-185) and with carboplatin 6/50 (12%; 95% confidence interval 525%). The response rates in previously treated small cell patients were O/16 and l/18, respectively. Overall, neither agent has pronounced activity in bronchogenic carcinoma. Bleomycin, vincrktine, mitomycin and cisplatin alternated with cyclophosphamide, 4’-epidoxorubicin and procarbazine in ad- vanced non-small-cell lung cancer. Demicheli R, Bonciarelli G, Jirillo A, Lonardi F, Balli M. Divisione di Rodioterapia e Oncologic, ULSS 28, 37045 Legnago. Tumori 1988;74:563-6. Thirty-eight patients with histologically confumed non-small-cell lung cancer were treated with bleomycin, vincristine, mitomycin and cisplatin (BOMP) alternated with cyclophosphamide, 4’-epidoxorubi- tin and procarbazine (CEP). Twenty patients were randomized to start tbe treatment with BOMP and 18 with CEP. Patients underwent a median of4 cycles (range, l-8). Theoverall response rate was 36% with 2 clinical complete responses. The median duration of response was 6.5 months, the median survival time was 7.5 months, and 37% of patients survived for more than one year. The comparison between the two arms of this study and between this study and a previous investigation on the effectivenessofBOMPsuggeststhatCEPregimenaddedtoBOMPdoes not significantly improve patient outcome.

In Vitro chemical eradication of small cell lung cancer: Application in autologous bone marrow transplantation

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110

Chemotherapy

In vitro chemical eradication of small cell lung cancer: Application in autologous bone marrow transplantation. Benard J, Bettan-Renaud L, Gavoille A, Pica J-L, Beaujean F, Lopez M, RiouG.Laboraroire&PharmncologieCliniqueetMoleculaire.InsN’tu~ Gustave Rowsy, 94800 Villejuif. Em J Cancer Clin Oncol 1988;24:1561-6.

Autologous bone marrow transplantation raises the question of the possible reinjection of tumour cells together with marrow. This paper investigates the ability of chemical compounds other than cyclo- phosphamide derivatives to eradicate small cell lung cancer (SCLC) in bone marrow. The responsiveness of SCLC lines to &-platinum, doxornbicin, VP16, Celiptiuma (an ellipticine derivative), Ditercalini- urna, a new drug belonging to the pyridocarbazole series, and Asta ZR were measured in agar-agar clonogenic assay. Cis-platinum and Diter- caliniun+’ exhibited a high tumouricidal effect. The low cloning efti- ciencies of SCLC lines in an agar-agar clonogenic assay did not allow turnout cells to be detected among bone marrow cells with sufficient sensitivity. Therefore cis-platinum and Ditercaliniuma were tested on bonemarrow-tumourcellmixturesculturedinaliquidmediumallowing the detection of one tumour cell par lad bone marrow cells. As cis- platinum exhibited a low myelotoxicity, it is proposed for purging bone marrows of patients with SCLC.

Results of palliative chemotherapy for advanced small cell bron- chial carcinoma. Ftitze D, Harjung H, Katz R, Kober B. Medizinische Klinik V, Stadtis- cheKliniken.6100Darmsfodt. DtschMedWochenschr1988;113:1663- 8.

Results of chemotherapy for small cell bronchial carcinoma were analyscxl retrospectively on 36 of 40 consecutive patients with the disease, admitted to an oncology unit between January 1985 and December 1987. The survival curves indicated a highly significant trend (logrankp=O.COl).Patients withextensivediseaseandKarnofskyindex of 40-50% had a median survival of four months, but for those with Kamofsky index > 50% it was 15 months. There was virtually no age difference between the two groups, but there were signilicant differ- ences regarding additional diseases (e.g. coronary heart disase, arterio- sclerosis,etc.),frcquencyofliverandCNS metastasesratesofcomplete or partial remission, number of early deaths, haematological toxicity, and severe weight loss (> 5 kg). These results suggest that aggressive chemotherapy (primarily designed for patients with limited disease) failed toimpmve thegraveprognosisofpatients with distant metastases and a low Karnofsky index (< 50%). Supportive care should be intensified for these patients.

Phase II trial of oral Idaruhicin in advanced non-small cell lung cancer (NSCLC). Ardizr.oniA,PmnzatoP,RepettoL, DePalmaM,CanobbioL,Gulisano M, Fusco V, Rosso R, Ganzina F. lstituto Nazionale per la Ricerca sul Concro, 16132 Geneva. Cancer Invest 1988;6:409-11.

The antitumoral activity and toxicity of a new daunorubicin analog (4-demethoxydaunorubicin, IMI 30, Idambicin) was tested in 20 con- secutivepatientswithnon-smallcelllungcancermosdypreu~tedwith chemotherapy. The drug was administered orally at a dose of 15 ms/m* for three days every 3-l weeks. Them were no clinical responses. Hematological and nonhematogical toxicities were mild.

Unexpected high toxicity in a phase II study of teniposide (VM-26) in elderly patients with untreated small cell lung cancer (SCLC). Cerny T, Pedrazzini A, Joss RA, Brunner KW. fnstitutfw Medirinische Onkologie der Universital Bern, Inselspital. CH-3010 Bern. Em J Cancer Clin Oncol1988;24:17914.

Teniposide (VM 26) as a single agent has shown promising results in the treatment of patients with small cell lung cancer. We treated 32 (30 evaluable) non-pretreated elderly and poor prognosis patients with

small cell lung cancer with teniposide 100 m&lay (30 min infusion) days l-5, every 3-4 weeks. Overall initial performance status was poor (WHO 2 or 3 in 62%). Extensive disease (ED) was documented in 50% including five patients with CNS metastases all of whom received simultaneous cranial irradiation. There was an unexpected high early death rate of 30% (9/30) including Eve patients with early toxic death due to severe bone marrow suppression leading to fatal septicaemia. The overall response rate was only 33% with no complete response. Where appropriate non-responding or relapsing patients received second line treatment with multidrug regimens *radiotherapy. The overall median survival was 5.6 months [ED: 1.7, limited disease (LD): 7.5 months]. Median response duration was 5.4 months (ED: 5.1, LD: 6.7 months). For responding patients median survival was 8.8 months (ED) and 11.5 months (LD). We conclude that in elderly and poor performance status patients singleagentteniposideas usedin thisstudy hasan unacceptable high early death rate and that the response rate is inferior to modem standard multidrug regimens.

Etoposide and split-dose cisplatin in bronchogenic carcinoma. LauerRC,FisherWB,PenningtonK,AnsariR,EinhomLH,LoehrerPJ. Department of Medicine, Indiana University. Indianapolis. IN 46223. Am J Clin Gncol. Cancer Clin Trials 1988;11:634-5.

The Hoosier Oncology Group (HOG) treated 13 patients with bron- chogenic carcinomaandan innovative schedule of cisplatin and VP-16. Unexpected toxicity was noted, and live deaths secondary to granulo- cytopenia and septic shock and three episodes of renal failure. Despite earlyclosureofLhisstudy,weconcludethatthisscheduleofcisplatinand VP-16 results in greater toxicity than comparable dosages in a more mutine schedule.

Randomized Phase II evaluation of iproplatin (CHIP) and carbo- platin (CBDCA) in lung cancer. A Southeastern Cancer Study Group trial. Kramer BS, Birch R, Greco A, Prestridge K, DeSimone P, Gmura G. University of Florida, Gainesville, FL. Am J Clin Oncol, Cancer Clin Trials 1988;11:643-5.

Cisplatin-containing regimens have shown activity in both small and non-smallcelllungcancer. WethereforeconductedarandomisedPhase II trial of the new platinum congeners iproplatin and carboplatin in bmnchogenic carcinoma. The overall response rate in chemothempy- naive non-small cell patients with iproplatin was 3/48 (6%; 95% confidence interval 2-185) and with carboplatin 6/50 (12%; 95% confidence interval 525%). The response rates in previously treated small cell patients were O/16 and l/18, respectively. Overall, neither agent has pronounced activity in bronchogenic carcinoma.

Bleomycin, vincrktine, mitomycin and cisplatin alternated with cyclophosphamide, 4’-epidoxorubicin and procarbazine in ad- vanced non-small-cell lung cancer. Demicheli R, Bonciarelli G, Jirillo A, Lonardi F, Balli M. Divisione di Rodioterapia e Oncologic, ULSS 28, 37045 Legnago. Tumori 1988;74:563-6.

Thirty-eight patients with histologically confumed non-small-cell lung cancer were treated with bleomycin, vincristine, mitomycin and cisplatin (BOMP) alternated with cyclophosphamide, 4’-epidoxorubi- tin and procarbazine (CEP). Twenty patients were randomized to start tbe treatment with BOMP and 18 with CEP. Patients underwent a median of4 cycles (range, l-8). Theoverall response rate was 36% with 2 clinical complete responses. The median duration of response was 6.5 months, the median survival time was 7.5 months, and 37% of patients survived for more than one year. The comparison between the two arms

of this study and between this study and a previous investigation on the

effectivenessofBOMPsuggeststhatCEPregimenaddedtoBOMPdoes

not significantly improve patient outcome.