Consolidation biochemotherapy for patients with advanced nonsmall cell lung carcinoma responding to induction PVM (cisplatin, vinblastine, mitomycin-C) regimen. A phase II study.

BACKGROUND: The authors investigated a consolidation biochemotherapy program with subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN alpha) biologic response modifiers (BRM) in patients with advanced nonsmall cell lung carcinoma (NSCLC) with responsive or stable disease to induction chemotherapy. METHODS: Patients with proven, advanced, previously untreated NSCLC were entered into the study. Induction chemotherapy consisted of cisplatin, 120 mg/m2 intravenously (i.v.), on Day 1; vinblastine, 6 mg/m2 i.v., on Day 1; and mitomycin-C, 6 mg/m2 i.v., on Day 1 (PVM), every 3 weeks. Subsequently, patients with complete response (CR), partial response (PR), and stable disease (SD) received consolidation biochemotherapy with subcutaneous rIL-2, 3 MU/m2 twice/day, and rIFN alpha, 3 MU once/day, 5 days a week, starting 2 weeks after the second PVM course. After 3 and 6 weeks of BRM treatment, patients had a 14-day rest period to intercalate consolidating PVM courses. RESULTS: Seventy-seven patients were enrolled in the trial. After 2 PVM induction courses, 16 patients progressed and went off the study, whereas 61 patients were eligible for consolidation biochemotherapy. Among the 61 patients, 9 were not treated with BRM for several reasons, whereas 52 patients began biochemotherapy and were evaluable for toxicity. Furthermore, a few days after starting BRM, 9 patients discontinued therapy due to side effects; the remaining 43 patients received adequate treatment and were fully evaluable. In the 52 evaluable patients, the following BRM related toxicities were observed: World Health Organization (WHO) grade 2-3 fever in 85% of patients, asthenia in 71%, anorexia in 63%, and flu-like syndrome in 18.5%. PVM-related vomiting was present in 19% of patients. WHO Grade 3-4 myelosuppression, from both BRM and PVM (overlapping toxicity), was anemia in 16% of patients, leukopenia in 12%, and thrombocytopenia in 19%. There were three toxic deaths: two due to BRM-induced hypotension and one from pneumonia. In the 43 fully evaluable patients (23 PR and 20 SD after induction chemotherapy), after a median of 6 weeks of biochemotherapy (range, 3-16 weeks), we observed 5 of 20 patients achieving PR from SD, and 6 of 23 with confirmed PR. In these 11 patients, the median duration of response was 21 weeks (range, 7-80 weeks). Overall response improvement was 11.6% in the 43 patients and 6.4% in the 77 total enrolled patients. Median survival was 41 weeks (range, 15-173 weeks) in the 43 patients and 38 weeks (range, 1.4-173 weeks) in the 77 patients. CONCLUSIONS: In this study, biochemotherapy, when administered by this dose and schedule, did not offer substantial benefit although it caused significant toxicity.