A prospective randomized phase III study in non-small-cell lung cancer comparing cisplatin, ifosfamide, vinblastine (VIP) versus cisplatin, ifosfamide and etoposide (VIP-16)

Background: It was recently reported that when ifosfamide was added to cisplatin and vinblastine the response rate was increased but not the survival in patients with non-small-cell lung cancer (NSCLC). The purpose of this study was to investigate the possibility of increased responses and survival with use of the combination of cisplatin, ifosfamide, etoposide (VIP-16) in comparison to the combination of cisplatin, ifosfamide, vinblastine (VIP) in non-operable NSCLC. Patients and methods: Two hundred twelve patients with histologically confirmed diagnoses of NSCLC were randomized into two groups: group A received cisplatin 100 mg/m(2), vinblastine 6 mg/m(2) and ifosfamide 3 mg/m(2) i.v. on day 1 every 3 weeks; group B received the same regimen except that etoposide 120 mg/m(2) was substituted for vinblastine on days 1, 2, and 3. Patients were well balanced for age, sex, performance status (PS), stage, grade, histology and sites of disease, and the relative dose intensity was similar in both groups. Results: One hundred one patients were evaluable for response in group A and 99 in group B. The overall response rates were 29% in group A (5CR) and 25% in group B (3CR). The median time to progression was 7.51 (2-35) months for group A and 7.7(1-28) months for group B (P = 0.34). The median survival was 8.49 (0.33-37.44) months for group A and 9.38 (0.43-36.59) for group B (P = 0.39). Multivariate Cox stepwise analysis showed stage to be the only significant prognostic factor for survival (P = 0.0114). Toxicity was not remarkable and not different between the two groups except for alopecia which was much more common in the patients who received etoposide. Conclusion: VIP and VIP-I6 combination chemotherapies are equally active in NSCLC with acceptable toxicity. Stage proved to be the most significant prognostic factor for survival in this study.