Phase I study of cisplatin and docetaxel plus mitomycin C in patients withmetastatic non-small cell lung cancer

Background: Docetaxel, cisplatin and mitomycin C are some of the active dru gs used in the treatment of patients with metastatic non-small cell lung ca ncer (NSCLC). The purpose of this study was to determine the maximum tolera ted dose (MTD) and recommended dose of the three drugs in combination for s uch patients. Methods: Chemotherapy-native patients with metastatic NSCLC were enrolled i n this study, The doses of docetaxel and cisplatin were fixed at 60 and 80 mg/m(2), respectively. It was planned to increase the dose of mitomycin C f rom 4 to 6 and 8 mg/m(2). AII drugs were administered on day I and repeated every 3-4 weeks, Results: All six patients received 60 mg/m(2) of docetaxel and 80 mg/m(2) o f cisplatin, three of them with 4 mg/m(2) of mitomycin C (level I) and the other three with 6 mg/m(2) of mitomycin C (level 2). Two of the three level 2 patients experienced dose-limiting toxicities (DLTs) in first cycle: feb rile neutropenia and grade 3 hyponatremia. Based on these data, the MTD was concluded to be 80 mg/m(2) for docetaxel, 80 mg/m(2) for cisplatin and 6 m g/m(2) for mitomycin C. Evaluation of the data from all of the cycles, howe ver, showed that four of the six patients experienced DLTs. Conclusions: The addition of mitomycin C to docetaxel and cisplatin resulte d in relatively high toxicities. It was impossible to use a high enough dos e of mitomycin C to improve the survival of NSCLC patients. We therefore co ncluded that further evaluation of this combination is unwarranted.