Combination chemotherapy in small cell lung carcinoma: A randomized study of two intensive regimens

From April, 1979 to November, 1981, 293 patients with small cell lung carcinoma (SCLC) were entered on a randomized, controlled study comparing the two induction regimens of high-dose CAV (HD-CAV) (cyclophosphamide [CTX] 1200 mg/m2, doxorubicin [ADR] 70 mg/m2 and vincristine [VCR] 1 mg/m2 intravenously (IV) on days 1 and 21) versus, conventional-dose CAV + VP-16 (etoposide) (CAV-VP) (CTX 1000 mg/m2, ADR 40 mg/m2, VCR 1 mg/m2 IV on days 1 and 21 with VP-16 100 mg/m2 on days 1–3, and 21–23). Responding and stable patients were continued on conventional-dose CAV for 5 consolidation courses. Prophylactic brain irradiation delivered after the first consolidation course in responders was optional. Patients were included in the study if they had extensive disease (i.e., beyond one hemithorax), no prior chemotherapy, or radiotherapy and performance status of 50 or above. After 2 induction courses, 215 cases are evaluable. Of these, 76 of 106 (72%) patients treated with HD-CAV have responded (>50% regression), including 13 complete responders (CRs) versus 80 of 108 (74%) patients on CAV-VP, including 15 CRs. Of the 130 evaluable patients who have completed consolidation (HD-CAV, 65; CAV-VP, 65), an additional 22 patients achieved CR (HD-CAV, 12; CAV-VP, 10) for an overall CR rate of 24%. Median duration of remission was 33.6 weeks for HD-CAV and 35.6 weeks for CAV-VP (P = 0.61). Median duration of complete response for HD-CAV was 33.8 weeks and for CAV-VP 36.7 weeks (P = 0.81). Survival curves were similar for the two regimens, with medians of 42.1 weeks for HD-CAV and 42.3 weeks for CAV-VP (P = 0.35). Survival correlated with performance status and quality of response. As anticipated, the major toxicity for both induction regimens was leukopenia. During induction, granulocyte nadirs of <500/mm3 occurred in 81% of patients on HD-CAV and 77% of patients on CAV-VP. Thus, dose intensification appears to produce high response rates and modest complete response rates in extensive SCLC, but it does not appear to improve materially survival compared to prior reports of conventional-dose therapy.