Phase I Study of Cisplatin and Docetaxel Plus Mitomycin C in Patients with Metastatic Non-small Cell Lung Cancer

Background: Docetaxel, cisplatin and mitomycin C are some of the active drugs used in the treatment of patients with metastatic non-small cell lung cancer (NSCLC). The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose of the three drugs in combination for such patients. Methods: Chemotherapy-native patients with metastatic NSCLC were enrolled in 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 from 4 to 6 and 8 mg/m 2 . All drugs were adminis­ tered on day 1 and repeated every 3-4 weeks. Results: All six patients received 60 mg/m 2 of docetaxel and 80 mg/m 2 of cisplatin, three of them with 4 mg/m 2 of mitomycin C (level 1) 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: febrile neutropenia and grade 3 hyponatremia. Based on these data, the MTD was con­ cluded to be 60 mg/m 2 for docetaxel, 80 mg/m 2 for cisplatin and 6 mg/m 2 for mitomycin C. Eval­ uation of the data from all of the cycles, however, showed that four of the six patients experienced DLTs. Conclusions: The addition of mitomycin C to docetaxel and cisplatin resulted in relatively high toxicities. It was impossible to use a high enough dose of mitomycin C to improve the survival of NSCLC patients. We therefore concluded that further evaluation of this combination is unwarranted.