Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer

A phase III randomized trial was conducted in patients with metastatic NSCLC, to determine if, in association with mitomycin (6 mg m(-2)) and ifosfamide (3 g m(-2)), the combination of moderate dosages of cisplatin (60 mg m(-2)) and carboplatin (200 mg m(-2)) - CarboMIP regimen - improved survival in comparison with cisplatin (50 mg m(-2)) alone - MIP regimen. A total of 305 patients with no prior chemotherapy were randomized, including 297 patients assessable for survival (147 in the MIP arm and 150 in the CarboMIP arm) and 268 patients assessable for response to chemotherapy. All but eight (with malignant pleural effusion) had stage IV disease. There was a 27% (95% CI, 19-34) objective response (OR) rate to MIP (25% of the eligible patients) and a 33% (95% CI, 24-41) OR rate to CarboMIP (29% of the eligible patients). This difference was not statistically significant (P = 0.34). Duration of response was not significantly different between both arms. There was also no difference (P = 0.67) in survival: median survival times were 28 weeks (95% Cl, 24-32) for MIP and 32 weeks (95% Cl, 26-35) for CarboMIP, with respectively 1-year survival rates of 24% and 23% and 2-year survival rates of 5% and 2%. The main toxicities consisted in emesis, alopecia, leucopenia and thrombocytopenia, that were, except alopecia, significantly more severe in the CarboMIP arm. Our trial failed to demonstrate a significant improvement in response or survival when patients with metastatic NSCLC were treated, in addition to ifosfamide and mitomycin, by combination of moderate dosages of cisplatin and carboplatin instead of moderate dosage of cisplatin alone. The results support the use of a moderate dose (50 mg m(-2)) of cisplatin in combination with ifosfamide and mitomycin for the chemotherapy of this disease.