Dose-finding study of fixed dose gemcitabine and escalating doses of ifosfamide given on days 1 and 8 in patients with advanced non-small cell lung cancer.

Abstract

This is a dose-finding study of fixed dose gemcitabine and escalating doses of ifosfamide, in chemo naïve patients with advanced non-small cell lung cancer. The purpose of the study was to determine the optimal dosage and the maximal tolerated dose (MTD) of a specified schedule of gemcitabine and ifosfamide. Patients received gemcitabine 1250 mg/m2 and ifosfamide between 1.6 and 2.2 g/m2, intravenously, on days 1 and 8, repeated every 3 weeks for a maximum of four cycles. RESULTS: Sixteen patients entered the study. Three patients were entered at the first dose level of ifosfamide (1.6 g/m2) and none experienced any dose limiting (DLT) toxicity. In dose level 2 (1.8 g/m2), two patients had grade IV haematological toxicities, but they reached 21 days without any other dose limiting toxicity (DLT). Three further patients entered at this level but they were withdrawn due to disease progression. The sixth patient entered without any DLT. Three patients entered dose level 3 (2.0 g/m2), without any grade IV toxicity. The first patient entered into dose level 4 (2.2 g/m2), had progressive disease within 21 days and was withdrawn and another three were entered and had no DLT during the first 21 days. Four (33%) of the patients had stable disease and 67% had progressive disease. CONCLUSION: The MTD of the ifosfamide gemcitabine combination was not reached in the present study, as no DLT was observed. This combination at the dose levels of this protocol has little or no activity in patients with advanced NSCLC.