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Cis-Platin~n and Vindesine in Combination in the Treatment of Non-Small Cell Lung Cancer. Carmichael, J., Gregor, A., Cornbleet, M. A. et al. Imperial Cancer Research Fund Medical Oncology Unit, Western General Hospital, Edinburgh, U.K. Eur. J. Cancer Clin. Oncol. 21: 811-814, 1985.

Sixty-three patients with advanced non-small cell carcinoma of the bronchus were treated with a combination of cis- platinum and vindesine. All patients had measurable disease and were of good per- formance status; none had received prior chemotherapy or radiotherapy. Thirty-three per cent of patients responded, with five patients achieving complete remission. Median duration of response was 4 months, with a median survival of 14 months in the responsers, compared with 6.5 months in the whole group and 4.8 months in the non-responders. Severe toxicity was en- countered, with alopecia, gastrointesti- nal toxicity and neurotoxicity common. Myelosuppression and renal toxicity were not dose-limiting. Thus the activity of this drug combination is confirmed, but severe toxicity precludes its widespread use in clinical practice.

Unresectable Non-Small Cell Lung Cancer Chemotherapy with Hi~-Dose Cisplatin and Etoposide. Scagliotti, G.V., Lodico, D., Gozzelino: F. et al. Institute of Internal Diseases, Department of Pulmonary Diseases, S. Lui- gi Gonzaga Hospital, I-i0042 Orbassano, Italy. Oncology 42: 224-228, 1985.

69 patients with unresectable non-small cell lung cancer, previously untreated, received cisplatin 100?mg/m on day 1 and etoposide 120 mg/m- on days 4, 6, 8, at 4-week intervals. 66 patients were evaluable for tumor response and toxicity. Overall objective response was 25.7% (3 complete responses and 14 partial respon- ses). Response rate in limited disease was 41% and in patients with performance score 0 it was 40%. Squamous cell carci- noma and adenocarcinoma responded in 31 and 24% of evaluable patients. Complete response was associated with a long dura- tion of remission. Median survival time of responding patients was significantly superior to the median of nonresponding patients (p < 0.001) but compared to stable disease no statistical significan- ce was demonstrable (p > 0.05). Hemato- logical and renal toxicity of proposed regimen was generally mild. Nausea and vomiting were the most noxious side ef- fects.

Comparison of Vindesine plus Cisplatin or Vindesine plus Mitomycin in the Treat-

ment of Advanced Non-Small Cell Lung Cancer. Shinkai, T., Saijo, N., Tominaga, K. et al. Depart- ment of Internal Medicine, National Cancer Center Hospital, Chuo-ku, Tokyo 104, Japan. Cancer Treat- ment Rep. 69: 945-951, 1985.

Fifty-eight patients with advanced non-small cell lung cancer ~ere randomly allocated to receive vindesine (39mg/m- every week) plus either cispla5 tin (80 mg/m" every 3 weeks) or mitomycin (8 mg/m- weekly x 3, then every 3 weeks). No patients achie- ved complete response. Among the 28 patients treat- ed with vindesine plus cisplatin, there were 12 partial responders (42.9%); among the 30 patients treated with vindesine plus mitomycin, there were only three partial responders (10%) (P < 0.005). Th4 median duration of response was ii.5 weeks (ran- ge, 4-25) in the patients treated with vindesine plus cisplatin. The median survival times for pa- tients treated with vindesine plus cisplatin and vindesine plus mitomycin were i0.I and 10.2 months, respectively; there was no statistical difference in survival time between the two groups. Initial performance status was the strong predictor of pa- tient survival. Toxic effects, including moderate myelosuppression, nephrotoxicity, peripheral neuro- pathy, and gastrointestinal symptoms, were generally manageable. The combination of vindesine and cis- platin appears to be effective against advanced non- small cell lung cancer.

Combination Chemotherapy with Bleomycin, Etoposide, and Cisplatin in Metastatic Non-Small-Cell Lung

Cancer. Osoba, D., Rusthoven, J.J., Turnbull, K.A. et al. " Toronto-Bayview Regional Cancer Centre, Toronto, Ont. M4N 3M5, Canada. J. Clin. Oncol. 3: 1478-1485,

1985. Fifty-three patients with recurrent and advanced

stage (III and IV) non-small-cell lung cancer (NSCLC) were treated with a combination of bleomycin, etoposide (VP-16-213), and cis-diamminedichloro- platinum (BEP). Forty-eight patients were apprai- sable for response. The response rates were 44% for the entire group, 57% in 30 patients with combined squamous-cell and large-cell carcinoma, and 22% in 18 patients with adenocarcinoma (40%, 50%, and 19%, respectively, if patients not appraisable for re- sponse are included as nonresponders). The median survival time of patients with squamous-cell and large-cell carcinoma was slightly longer than that of patients with adenocarcinoma (23 weeks v 19 weeks) Patients with responsive disease survived signifi- cantly longer (median, 34 weeks) than did patients with unresponsive disease (median, 1'6 weeks) ~ = .001). In the entire group, the median survival time of patients with an Eastern Cooperative Onco- logy Group (ECOG) performance status of 0 or 1 was better (23 weeks) than of those with a status of 2 or 3 (15 weeks), but this difference was not seen in the subgroup with squamous-cell and large-cell carcinoma (24 weeks v 23 weeks, respectively). Thus, the performance status was not of prognostic value in the histologic subgroups experiencing the best response rate. There were two treatment-related deaths, but otherwise the toxicity of BEP was

229

acceptable. Only four of the 119 treated

cycles were followed by fever even though there was significant neutropenia (0.5 x i0 /i) after 20 of 97 treatment cycles. The majority of patients receiving BEP ex- perienced relief of cough, hemoptysis, pain, and fatique associated with their disease. There was a good correlation be- tween objective responses and palliation of symptoms. Thus, BEP offers good palli- ation, particularly for patients with squamous-cell and large-cell lung cancer.

Doxorubicin, Cyclophosphamide, CCNU, and Vincristine With or Without Cisplatinum in Non-Small Cell Lung Cancer. Chlebowski, R.T., Herrold, J., Ali, I. et al. Division of Medical Oncology, Harbor -UCLA Medical Center, Torrance, CA 90509, U.S.A. Am. J. Clin. Oncol., Cancer Clin. Trials 8: 157-161, 1985.

To evaluate the role of cisplatinum in the treatment of advanced non-small cell lung cancer, 48 patients received ~ither a doxorubicin (adriamycin~ 50 mg/m- i.v.,

cyclophosphamide 3002mg/m- i.v., lomu- stine (CCNU) 50 mg~m p.o., vincristine (oncovin) 1.2 mg/m i.v. (ACCO) combina- tion or2the same drugs plus cisplatinum 50 mg/m i.v. (PACCO) in a prospective sequential trial. No patient had received prior chemotherapy. Patients receiving the two regimens were comparable with regard to median age~performance status, histo- logic subtype, disease extent, and weight loss. Objective response frequency was only 5% in the initial 20 patients re- ceiving ACCO treatment compared to a re- sponse frequency of 28% (7% complete) in the 28 patients receiving cisplatinum in the PACCO treatment arm (p < 0.06). Patients achieving objective response li- ved significantly longer than nonrespon- ders (9.1 months vs. 3.8 months, p < 0.05). Although median survival was similar on the two regimens (6.1 months for ACCO vs. 7.6 months for PACCO), more than four times as many patients were alive after l year in the PACCO treatment group (24% vs. 5%). Predominant toxicity consisted of moderately severe nausea and vomiting (63% on PACCO vs. 34% on ACCO, p < 0.05)~ and myelosuppression with WBC < 3,000/mm- occurring in the majority of patients on both regimens. These results suggest cis- platinum addition to a doxorubicin, cyclo- phosphamide, lomustine, and vincristine combination may be associated with in- creased 1-year survival in the non-small cell lung cancer patient population.

8, RADIOTHERAPY

Prophylactic Versus no Brain Irradiation in Regional Small Cell Lung Carcinoma.

Seydel, H.G., Creech, R., Pagano, M. et al. Henry Ford Hospital, Detroit, MI 48202, U.S.A. Am. J. Clin. Oncol., Cancer Clin. Trials 8: 218-223, 1985.

Among 104 complete responders entered in a ran- domized prospective trial of treatments for regio- nal small cell undifferentiated carcinoma of the lung, 52 received prophylactic irradiation of the brain, 3,000 tad in i0 fractions, and 52 did not. The median survivals were 53 and 52 weeks respec- tively, and the incidences of brain metastases were 5% and 20%. Prophylactic brain irradiation was not associated with significant long-term toxicity.

Whole Brain Irradiation for Metastases from Lung Carcinoma: A Clinical Investigation. Chatani, M., Teshima, T., Hata, K. et al. Depart- ment of Radiation Therapy, The Center for Adult Diseases, Osaka 537, Japan. Acta. Radiol., Ser. Oncol. 24: 311-314, 1985.

Sixty-nine consecutive patients with brain meta- stases from lung carcinoma were randomly allocated to one of the two radiation therapy schedules: 30 Gy/10 fractions/2 weeks or 50 Gy/20 fractions/4 weeks. The improvement rate for neurologic function was similar in the two groups. The median survival

times for patients receiving the short course and the long course were 4 months and 3 months, respec- tively. The half-year survival rate was 42 per cent after the short course and 14 per cent after the long course (p < 0.05). Performance status and lac- tate dehydrogenase were other factors which signi- ficantly influenced the half-year survival rate.

9, COIVBINED TREATMENT MODALITIES

Adverse Effect of Intrapleural Corynebacteri~n Pa1~a~n as Adjuvant Therapy in Resected Stage I and II Non-Small Cell Carcinoma of the Lung. Kaufmann, M., Stjernsward, J., Zimmermann, A. et al. Ludwig Institute for Cancer Research, Inselspital, 3010 Bern, Switzerland, J. Thorac. Cardiovasc. Surg. 89: 842-847, 1985.

Intrapleural Corynebacterium parvum 7 mg or pla- cebo was administered postoperatively as adjuvant therapy to patients with resected Stage I and II non-small cell lung cancer in a prospective, rando- mized, multicenter trial. A total of 475 patients were entered into this study between July, 1977, and February, 1979. Of this group, 405 can be evalu- ated, with an average follow-up time of 4.6 years. More side effects, especially fever and chest pain, were observed in patients receiving Corynebacterium parvum (p < 0.001). An increase in fever was asso- ciated with a decrease in survival (p=0.01). Life- threatening or fatal complications were not seen. Important prognostic factors are surgical stage (p < 0.001) and degree of differentiation (p=0.02). Corynebacterium parvum is associated with a decrea- sed survival (p=0.02). It is concluded that intra- pleural Corynebacterium parvum is detrimental to

survival.

Combined ~bdality Therapy with Radiotherapy, Chemo- therapy, and I~nunotherapy in Limited Small-Cell