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 NSCL C, to determine if, in association with mitomycin (6 mg m(-2)) and ifosfami de (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 i n comparison with cisplatin (50 mg m(-2)) alone - MIP regimen. A total of 3 05 patients with no prior chemotherapy were randomized, including 297 patie nts 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 patien ts) and a 33% (95% CI, 24-41) OR rate to CarboMIP (29% of the eligible pati ents). This difference was not statistically significant (P = 0.34). Durati on of response was not significantly different between both arms. There was also no difference (P = 0.67) in survival: median survival times were 28 w eeks (95% Cl, 24-32) for MIP and 32 weeks (95% Cl, 26-35) for CarboMIP, wit h respectively 1-year survival rates of 24% and 23% and 2-year survival rat es of 5% and 2%. The main toxicities consisted in emesis, alopecia, leucope nia and thrombocytopenia, that were, except alopecia, significantly more se vere in the CarboMIP arm. Our trial failed to demonstrate a significant imp rovement in response or survival when patients with metastatic NSCLC were t reated, in addition to ifosfamide and mitomycin, by combination of moderate dosages of cisplatin and carboplatin instead of moderate dosage of cisplat in alone. The results support the use of a moderate dose (50 mg m(-2)) of c isplatin in combination with ifosfamide and mitomycin for the chemotherapy of this disease. (C) 2000 Cancer Research Campaign.