Phase I/II study of cisplatin, ifosfamide and irinotecan with rhG-CSF support in patients with stage IIIB and IV non-small-cell lung cancer

Purpose: We conducted a phase I/II study in previously untreated patients w ith stage IIIB or IV nonsmall-cell lung cancer (NSCLC) to: (1) determine th e maximum tolerated dose (MTD) of cisplatin combined with a fixed schedule of ifosfamide and irinotecan with rhG-CSF support; and (2) to determine the overall response rate and median survival of patients entered on this stud y. Methods: Ifosfamide (1.5 g/m(2)) and irinotecan (60 mg/m(2)) were admini stered at fixed doses on days 1-4 and on days 1, 8 and 15, respectively. Ci splatin was given on day 1 at 60 mg/m(2) and was increased in 10-mg/m(2) in crements. This regimen was repeated every 4 weeks. rhG-CSF (nartograstim) w as administered subcutaneously at a dose of 1 mu g/kg on days 5-18 except o n the day of irinotecan treatment. Results: Between June 1995 and April 199 8, 46 patients were registered onto this phase I/II study. The MTD of cispl atin was defined according to toxicity and the dose during three courses wa s increased. Since at the 80 mg/m(2) dose level more than one-third of the patients were treated with dose modification, the dose of 70 mg/m(2) was re commended for phase II study. The dose-limiting toxicity was leukopenia. Th e overall response rate was 62.2% (95% CI 48.0-76.4%), the median response duration was 144 days, and the median survival time was 393 days. Conclusio n: For phase II study, we recommend doses of cisplatin 70 mg/m(2) on day 1 combined with ifosfamide and irinotecan with rhG-CSF support. Both the resp onse rate and preliminary survival data in this study suggest a high degree of activity of this combination in previously untreated NSCLC.