Sequential treatment with vindesine–ifosfamide–platinum (VIP) chemotherapy followed by platinum sensitized radiotherapy in stage IIIB non-small cell lung cancer: A phase II trial

Purpose: Daily administration of cisplatin concomitant with radiotherapy improved the overall survival in inoperable non-small cell lung cancer (NSCLC) in one EORTC study. In this study, we prospectively investigated the efficacy and toxicity of a sequential treatment with three cycles of vindesine–ifosfamide–platinum (VIP) induction chemotherapy, followed by daily cisplatin-sensitized radiotherapy. Methods: Between June 1993 and June 1995, 23 previously untreated patients with stage IIIB NSCLC with World Health Organization performance status 0 or 1 were included. Chemotherapy consisted of platinum 30 mg/m2 and ifosfamide 1200 mg/m2 i.v. on days 1, 2 and 3, and vindesine 3 mg/m2 i.v. on days 1 and 8, every 4 weeks. After three cycles and at least stable disease, radiotherapy was started (30 Gy in 10 fractions, followed by a boost of 22 Gy in 10 fractions). Each fraction was preceded by Platinum 6 mg/m2 i.v. Results: Nineteen patients completed the sequential therapy. One patient died from neutropenic sepsis during the first cycle of chemotherapy, and three patients had progressive disease after chemotherapy. The overall response rate after sequential therapy was 47% (95% confidence interval 24–80), median survival was 10.6 months, 1- and 2-year survival rates were 47 and 16%, respectively. Major toxicity consisted of neurotoxicity grade III–IV in 18% and of leukopenia grade III–IV in 22% of the patients. Acute radiation pneumonitis grade III occurred in 11% of the patients. Conclusion: Three-drug VIP induction chemotherapy followed by cisplatin-sensitized radiotherapy is feasible, with acceptable, albeit substantial, toxicity. In spite of the theoretically promising sequence of therapies, survival results remain disappointingly low.