A prospective randomised study in limited disease small cell carcinoma--doxorubicin and vincristine plus either cyclophosphamide or etoposide.

A prospective randomised study was undertaken in patients with limited disease small cell carcinoma of the lung (SCCL), which compared doxorubicin, 50 mg/m2, and vincristine, 2 mg i.v. (intravenously) on day 1, with either cyclophosphamide, 800 mg/m2 on day 1 (CAV) or etoposide, 60 mg/m2 i.v. on day 1 and 120 mg/m2 orally on days 2-5 (AVE). Responding patients were to receive six cycles of chemotherapy at 3 weekly intervals followed after 2 weeks by mediastinal irradiation. Response rates and toxicity were evaluated by the chi square or Fisher's exact test and survival by the logrank test. 81 patients were entered into the study, 38 of whom received CAV and 43 received AVE. In the patients treated with CAV and AVE, the overall response rate was 61% (confidence limit (CL), 45-71%) and 74% (CL, 61-87%) respectively, the complete response rate was 32% (CL, 17-47%) and 51% (CL, 36-66%), respectively (P = 0.07) and the median survival was 12 and 14.5 months, respectively (P = 0.15). In the patients treated with CAV and AVE, the incidence of grade 3 and 4 leucopenia was 29% (CL, 15-43%) and 9% (CL, 0-18%), respectively (P = 0.025). No patient developed doxorubicin cardiomyopathy. These findings support the role of etoposide in first line chemotherapy for SCCL. AVE is among the more efficacious regimens for SCCL and also has a relatively low toxicity.

Prospective study of etoposide scheduling in combination chemotherapy for limited disease small cell lung carcinoma.

78 patients with limited disease small cell lung carcinoma (SCLC) were entered into a prospective randomised study of two combination regimens (AVE-5 and AVE-1) that differed only in the scheduling of etoposide. Patients in the AVE-5 arm received etoposide intravenously 60 mg/m2 on day 1 and orally 120 mg/m2 on days 2-5 of each cycle. Patients in the AVE-1 arm received etoposide 300 mg/m2 intravenously on day 1. Patients in both arms received doxorubicin and vincristine on day 1 of each cycle. The complete (53% vs. 26%) and the overall (75% vs. 52%) response rates were significantly higher in the AVE-5 arm. Median survival was also increased from 11 to 14 months in this arm. Toxicity was low and similar in both groups. The daily administration of etoposide in low toxicity combination therapy for SCLC is important. This can be conveniently achieved by using etoposide orally.

Palliative radiation for stage 3 non-small cell lung cancer--a prospective study of two moderately high dose regimens.

Eighty four patients from Groote Schuur Hospital and Frere Hospital East London were entered into a prospective randomised trial between January 1990 and December 1993. All the patients possessed non-small cell carcinoma (NSCLC) of the lung too extensive for radical irradiation and World Health Organization performance status 0-2. The patients were randomised to receive either 35 Gy in 10 fractions (43 patients) or 45 Gy in 15 fractions (41 patients). In the patients treated to 35 Gy and 45 Gy, the median survival was 8.5 months in both groups, the symptomatic response rate was 68% and 76% and the incidence of moderate to severe radiation oesophagitis was 23% and 41% respectively. The latter approached statistical significance (P = 0.07, chi square). There was no evidence of a dose response effect on survival in the moderate dose range in patients treated palliatively for locally advanced NSCLC.

Concurrent radiation and weekly cisplatin for non-small-cell lung cancer--a phase I/II study.

A total of 20 patients with loco-regional non-small-cell lung carcinoma were entered into a study of irradiation (3.0 Gy x 15 doses to a total dose of 45 Gy given in 4 fractions per week on days 1, 2, 4 and 5 of each week) and cisplatin given at a dose of 40 mg/m2 on day 3 of each week for a total of three infusions. One patient who had stage 1 disease showed a complete response to therapy and is alive and clear of disease at 35 months. In 19 patients with stage 3 disease, the complete response rate was 16% and the partial response rate was 42%. The rate of 1-year survival was 42% and the rate of 2-year survival was 11%; the median survival of these patients was 11 months. Relapse occurred, mostly at metastatic sites, in 10 of the 11 patients who responded to therapy. Acute toxicity was modest and tolerable by our patients. No severe late toxicity was encountered, and none of the patients developed grade 3 dyspnoea (an inability to walk 100 yards because of breathlessness) while clear of recurrent disease. Changes in lung function observed at follow-up examinations were similar to those seen after irradiation alone. Weekly administration of cisplatin is therefore feasible in patients receiving a continuous course of irradiation. The high relapse rate observed in responding patients indicates the need for evaluation of the efficacy of combination chemotherapy in the adjuvant or neo-adjuvant setting.