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Page 1: Combination chemotherapy + split-dose radiotherapy in non-operable non small cell bronchogenic carcinoma

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RT approximately 65% of the expected dosa- ge could be administered. 50% of VLB could

be given on long term follow-up although all pts experienced some degree of neuropathy (mostly not exceeding grade i) on the WHO scale.

Alternation of Radiotherapy and Chemothera- py in Stage Ill Non-Small Cell Bronchogenic Carcinoma (NSCBC). Arcangeli, G., Nervi, C., Righini, R., Ti- rindelli, D. Instituto Medico e di Ricerca Scientifica, Rome, Italy.

Fiftytwo patients with stage III NSCBC have been treated by alternating radiothe- rapy and chemotherapy. Radiotherapy was given as three 200 cGy fractions on days 1 and 2, 8 and 9, 22 and 23, and 29 and 30, for a total dose of 48 Gy. A three dr~q combination of cyclo~hosphamide (400 mg/m ), doxorubi~in (17 mg/m ) and methotrexate (15 mg/m-) was given on days 3 and 24 and repeated thereafter every 21 days. An im- provement of performance status (PS) was observed in 22 patients assigned to PS categories equal or less than 80. Six (11.5%) and 29 (56%) patients underwent complete or partial response, respective- ly. Minor response or progression were ob- served in 17 patients (32.7%). The median lifespan, evaluated by means of the Kaplan and Meier product limit method, was 41 weeks. More than one third of patients was still alive at 1 year. The estimated median lifespan for responding patients was 61 weeks and for non responding pa- tients was 27.6 weeks. The difference was statistically significant. Most of the pa- tients had very mild or no side effects.

Combined Modality Treatment by Chemothera- py (CT) and Radiation Therapy (RT) of Pre- viously Untreated Stage III Squamous Cell Lung Cancer. Osoba, D., Rusthoven, J.J., Shepherd, F.A., Evans, W.K., Berry, M.P., Catton, P.A., Ackerman, I., Turnbull, K. Toronto-Bayview Regional Cancer Centre, Sunnybrook Medical Centre and Toronto General Hospital, Toron- to, ON, Canada, M4N 3M6.

Ct consisting of bl~omycin (B) i0 u/m 2, etoposide (~) i00 mg/m- and cis-platinum (P) 25 mg/m-, given daily x ~-~every 4 wk for 2 cycles, was followed in 4 wk by RT 2000 cGy in 5 fractions, a 4 wk rest interval, and further RT at the radiation oncologists discretion. Twenty-one patients (lo male, ii

female; median age 62 yr; range 50-73 yr) have been entered into this pilot study. ECOG performance status was 0 in 2 patients and 1 in 19 patients. Eighteen patients com- pleted 2 cycles of BEP; in 2 patients the second cycle was not given because of dis- ease progression and 1 patient refused a

second cycle. All 21 patients were apprai-

sable for toxicity and response after BEP. The- re were no CT treatment-related deaths. Myelo- suppression was the most frequent toxic effect; 2 patients developed pneumonia. There were 2 complete and 9 partial responses (52%); 3 pa- tients had disease progression. Seventeen pa- tients received RT (i was not treated because of rapid disease progression after the second cycle of CT) and 3 patients are still on treat- ment. Six patients received only 2000 cGy be- cause of disease progression during the 4 wk rest interval. Eleven patients received a fur- ther 2000 cGy. Eight of 17 patients had further improvement in disease status after RT. Signi- ficant pulmonary toxicity attributable to B + RT was found in only 1 patient. Median survi- val is 12 mo; 3 patients have survived > 24 mo. Th~s combined modality approach could be test- ed versus RT alone in a phase III trial.

Trial of a Synchronized Combination of Low- Dose Adriamycin and Split-Course Irradiation for Inoperable Lung Cancer. Lagrange, J.L., Verschoore, J., Boublil, J.L., Aubanel, J.M., Blaive, B., Namer. M. Centre Antoine Lacassagne, Nice 06054, France.

Split-course irradiation of inoperable lung cancer has produced response rates approaching 50% (Int. J. Radiat. Onc. Biol. Phys. i: 1107- 1118, 1976). Chemotherapy has given reported rates of 40% (Ann. Int. Med., 95: 414-420, 1981; Cancer, 37: 1237-1242, 1976). A trial was the- refore initiated to assess the efficacy of a synchronized combination of adriamycin and ir- radiation, the aim being to increase the num- ber of objective locoregional responses.

In 1980, 27 patients (mean age 61.2 years) with inoperable lung cancer (i stage I, 20 stage III, 6 stage IV UICC) were treated with two series of 20 Gy (5 x 4 Gy) at a three week interval; one hour before each session each patient received an iv injection of adriamy- cin (i0 mg/m ). Histologically, there were 25 epidermoid cancers and 2 oat cell carcinomas.

Response was evaluated radiologically and by fibroscopy one month after treatment; objec- tive responses (complete response CR + parti- al response PR) were obtained in 62% of cases, including 16% CR. No instances of tumor pro- gression were observed.

Survival: average survival was 16 weeks, but increased to 26 weeks for CR and PR pati- ents. At 6, 12 and 18 months there were re- spectively 40%, 10% and 5% of the patients still alive. Fourteen radiation-induced pneumopathi- es occurred, 4 of which were the cause of death.

Conclusion: TILe response rate was at least as good as that achieved with other therapeu- tic modalities, but the severe toxicity e~- plains the mediocre survival of our patients. This trial confirms the fact that low-dose adriamycin is a powerful radiosensitizer.

Combination Chemotherapy + Split-Dose Radio-

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therapy in Non-Operable Non Small Cell Bronchogenic Carcinoma.

Helle, P.A., Planting, A.S.Th. The Dr. Da- niel den Hoed Cancer Center/Rotterdam Radio- Therapeutic Institute, P.O. Box 5201, Rot- terdam, The Netherlands. A pilot study of the EORTC Lung Cancer Cooperative Group (Chairman: Dr. J.E. MC Vie; Secretary Dr. N. van Zandwijk).

In 1983 an EORTC pilot study with high dose chemotherapy followed by high dose split course radiotherapy in inoperable non-oatcell bronchogenic carcinoma was started in the Rotterdam Radio-Therapeu- tic Institute.

The chemotherapy ~egimen consisted of cis-pl~tin i00 mg/m (day i); vindesine 3 mg/m (day 1 and 8). The treatment starts with 2 chemotherapy courses follow- ed by radiotherapy (TD: 55 Gy). In the split interval of the radiotherapy a third cycle of chemotherapy was given.

Seventeen patients have completed the protocol with a follow-up time of minimal 12 months.

After the 2 chemotherapy courses 3 of the 17 patients had a PR; 9 patients were in regression; 5 patients were NC. There was no progressive disease after the che- motherapy. 10/17 patients are alive; 4 with progressive disease. The mean survi- val of the whole group is 13+ months.

In 3/17 patients a dose reduction of the vindesine was necessary due to severe leu- kopenia. 3/17 patients suffered from seve- re gastro-intestinal toxicity. All patients suffered moderate weight loss during the chemotherapy. There was no significant neu- rotoxicity. No enhancement of the radiation toxicity was seen.

On the basis of this phase II experience a randomized phase II study is started in the EORTC Lung Cancer Group.

Combined Chemotherapyy With Cyclophospha- mide, Adriamycin and Cisplatin (CAP) and Radiotherapy in Non-Small Cell Lung Cancer. Yoneda, S., Homma, T., Yoshida, S., Nogu- chi, Y., Fukuda, Y., Nakata, M., Sakura, M., Nishimura, H., Yamamoto, M. Saitama Cancer Center, Saitama, Japan.

Combined Chemotherapy containing eispla- tin and radiotherapy was performed in pati- ents with non-small cell lung cancer to e- valuate its possible synergistic effect. We treated 75 patients with inoperable non- small cell lung ~ancer by CAP (cyclop~os- phamide 400 mg/m-, a~riamycin 30 mg/m- and cisplatin 50-75 mg/m q 4 weeks). Betame- thasone was administered as an antiemetic. 37 patients received radiotherapy (5,000- 7,000 rad in 5-7 weeks) between the initi- al 2 courses of CAP. 12 patients were non- evaluable; 6 patients had nonmeasurable tumors, and 6 patients received only 1

course of CAP.

C ~ a lone C~+RT o v e r a l l No. of pat£ . . . . 38 37 75 mecl~n per formmlm~ s c o r e 1 I 1 median stage IV Ill IV No. of evaluable par.ients 29 34 63 complete response 0 9 9 partial response 6 19 25 responsa rate (%) 21 {p<O.O01) 82 45 median duration of response 3 7 6 median survival (months) I0 (p<O.05) ]6 ]2

The initial sites of re{apse during the tre- atment were the primary lesion in 4 patients, the brain in 3, the lymph node in 2, the lung in 1 and the bone in I. The median survival time was 29 months for 9 complete responders, 13 months for 25 partial responders (p < 0.005), and 7 months for 29 nonresponders (p < 0.005). Side effects were nausea and vomiting (83%), leucopenia (76%) and radiation pneumonitis (72% in CAP+RT group). Nephrotoxicity was mild and transient.

Surgery and Chemotherapy in Lung Carcinoma. Ex- perience About 7~ Patients. ~ Raut , ~., Zabbe-, CI_, Larzul-, J.J , Guillerm-, D - Z " ., Rio , G., Clavier , J. i. Department of Tho- racic Surgery, Clinique Pasteur and Chru Brest, and Department of Pneumology. 2. Chru Brest. 3. Ch Quimper and 4. Hia Brest, France.

Since April 1981 to December 1984, 78 pa- tients with epidermoid lung carcinoma underwent surgery after chemotherapy. Schedules of drugs all included Cisplatinum, every 21 days. On an average, operation was performed 90 to 120 days after diagnosis, and 3 to 4 weeks after the last treatment.

Staging was evaluated at the diagnosis, and compared to preoperative TNM to evaluate ob- jective responses, and to postoperative patholo- gical staging.

Among responders, 8 non operative patients underwent curative surgery after treatment and 12 were save of all tumor cells.

Operative technic was not modified by pre- operative chemotherapy. Types of procedures were following 38 lobectomies, 25 pneumonecto- mies, 8 resections of a segment, and 8 explo- ratomy thoracotomies. The hospital mortality was 4%, without others major complications.

Conclusion: Preoperative chemotherapy is a feasible treatment without major complications. Principal interest is the control of locoregi- onal disease, and in some cases it permits lung resection for unoperative patients.

Combination of Chemotherapy and Surgery For Small Cell Lung Cancer (SCLC) With Limited Dis- ease. Paccagnella, A., Fiorentino, M.V., Brandes, A., Sotti, G., De Besi, P., Fosser, V.P., Rea, F., Calabro, F., Sartori, F. Dipartimento Oncologi- co - U.L.S.S. no 21, 35100 Padova, Italy.

From November 1982 to January 1985, 75 pa-

tients with histologically proven SCLC entered


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