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 p rogram with subcutaneous recombinant interleukin-2 (rIL-2) and recombi nant interferon-alpha (rIFN alpha) biologic response modifiers (BRM) i n patients with advanced nonsmall cell lung carcinoma (NSCLC) with res ponsive or stable disease to induction chemotherapy. METHODS. Patients with proven, advanced, previously untreated NSCLC were entered into t he study. Induction chemotherapy consisted of cisplatin, 120 mg/m(2) i ntravenously (i.v.), on Day 1; vinblastine, 6 mg/m(2) i.v., on Day 1; and mitomycin C, 6 mg/m(2) i.v., on Day 1 (PVM), every 3 weeks. Subseq uently, patients with complete response (CR), partial response (PR), a nd stable disease (SD) received consolidation biochemotherapy with sub cutaneous rIL-2, 3 MU/m(2) twice/day, and rIFN alpha, 3 MU once/day, 5 days a week, starting 2 weeks after the second PVM course. After 3 an d 6 weeks of BRM treatment, patients had a 14-day rest period to inter calate consolidating PVM courses. RESULTS. Seventy-seven patients were enrolled in the trial. After 2 PVM induction courses, 16 patients pro gressed and went off the study, whereas 61 patients were eligible for consolidation biochemotherapy. Among the 61 patients, 9 were not treat ed with BRM for several reasons, whereas 52 patients began biochemothe rapy and were evaluable for toxicity. Furthermore, a few days after st arting BRM, 9 patients discontinued therapy due to side effects; the r emaining 43 patients received adequate treatment and were fully evalua ble. In the 52 evaluable patients, the following BRM related toxicitie s 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 Gr ade 3-4 myelosuppression, from both BRM and PVM (overlapping toxicity) , was anemia in 16% of patients, leukopenia in 12%, and thrombocytopen ia in 19%. There were three toxic deaths: two due to BRM-induced hypot ension 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 a chieving PR from SD, and 6 of 23 with confirmed PR; In these 11 patien ts, 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, 1 5-173 weeks) in the 43 patients and 38 weeks (range, 1.4-173 weeks) in the 77 patients. CONCLUSIONS. In this study, biochemotherapy, when ad ministered by this dose and schedule, did not offer substantial benefi t although it caused significant toxicity. (C) 1996 American Cancer So ciety.