Purpose: To determine whether the addition of ifosfamide to cisplatin plus etoposide improves the response rate, time to disease progression, or overall survival in previously untreated patients with extensive-stage small-cell carcinoma of the lung (SCLC).
Patients and methods: Patients with extensive SCLC with a Karnofsky performance score (KPS) > or = 50 and adequate renal function and bone marrow reserve were eligible. Patients with CNS metastases were eligible and received concurrent whole-brain radiotherapy. Patients were randomized to receive cisplatin (20 mg/m2) plus etoposide (100 mg/m2) (VP) both given intravenously (i.v.) on days 1 to 4 or cisplatin (20 mg/m2), ifosfamide (1.2 g/m2), and etoposide (75 mg/m2) (VIP) all given i.v. on days 1 to 4. Cycles were repeated every 3 weeks for four cycles.
Results: From May 1989 through March 1993, 171 patients were randomized (84 to VP and 87 to VIP). The median follow-up duration is 26 months. All patients were assessable for survival; 163 were fully assessable for response and 162 for toxicity. Myelosuppression was greater with VIP. Objective responses were observed in 55 of 82 (67%) and 59 of 81 (73%) assessable patients treated with VP and VIP, respectively (difference not significant). The difference in the median time to progression was statistically different (P = .039). The median survival times on VP and VIP were 7.3 months and 9.0 months, respectively (P = .045 for survival curves by stratified log-rank test) with 2-year survival rates of 5% versus 13%, respectively.
Conclusion: VIP combination chemotherapy is associated with an improved time to progression and overall survival over VP therapy in patients with extensive SCLC.