Phase I study of cisplatin, ifosfamide and irinotecan with rhG-CSF support in advanced non-small cell lung cancer.

A phase I study was conducted in advanced non-small cell lung cancer to determine the maximum tolerated dose (MTD) of irinotecan combined with a fixed schedule of cisplatin and ifosfamide with rhG-CSF support. In addition, efficacy including survival time was evaluated at 2 years after the completion of patient registration. Cisplatin (20 mg/m2) and ifosfamide (1.5 g/m2) were administered at fixed doses on days 1-4, and irinotecan was given on days 1, 8 and 15 starting at 40 mg/m2, which was increased in 10 mg/m2 increments. This regimen was repeated every 4 weeks. rhG-CSF was administered subcutaneously at a dose of 50 microg/m2 on days 5-18 except on the day of irinotecan treatment. Forty-five patients were registered and 35 had received no prior chemotherapy. MTD or irinotecan was defined according to toxicity and the dose during three courses was increased up to 70 mg/m2. The dose 60 mg/m2 was recommended for phase II study. The dose-limiting factor was thrombocytopenia. The overall response rate was 57.8% and the median survival time was 492 days. In chemotherapy-naive patients, the response rate was 65.7% (95% CI; 50-81.4%), median response duration 161 days, median survival time 513 days, 1-year survival rate 62.4%, and 2-year survival rate 27.3%.