IFOSFAMIDE PINS PACLITAXEL IN ADVANCED NON-SMALL-CELL LUNG-CANCER - APHASE-I STUDY

Background: Ifosfamide and paclitaxel are active drugs in the manageme nt of non-small-cell lung cancer. We have per formed a phase I study u sing a fixed dose of ifosfamide with escalating doses of paclitaxel, w ith G-CSF support, in an effort to determine the maximum tolerated dos e (MTD) of paclitaxel in this combination, and to describe the dose-li miting toxicities of the combination at the recommended phase II dose of paclitaxel. We also studied the feasibility of delivering the pacli taxel as a one-hour infusion at the recommended phase II dose. Patient s and methods: Thirty-one patients were treated, 25 with stage IV dise ase, and 6 with stage IIIB disease. Ifosfamide was administered at a d ose of 1.6 g/m(2) i.v. bolus daily x 3 days, with mesna uroprotection. Paclitaxel was administered as a 24-hour infusion at dose levels of 1 35, 170, 200, 250, and 300 mg/m(2); six patients were treated with a o ne-hour infusion, at a dose of 250 mg/m(2). G-CSF, 5 mu g/kg, was admi nistered subcutaneously on days 4 through 10, or until the absolute ne utrophil count exceeded 4000/mu l. Cycles were repeated every 21 days. Results: The dose-limiting toxicity was granulocytopenia, which incre ased with increasing dose levels of paclitaxel. The MTD was 300 mg/m(2 ) of paclitaxel, and the recommended phase II dose 250 mg/m(2) adminis tered as a 24-hour infusion. Other toxicities were generally mild, wit h only 5 patients demonstrating grade 3 neurotoxicity and 5 with grade 3 thrombocytopenia. Partial responses were seen in seven patients (23 %), all in the 18 patients who received dose levels of 250 mg/m(2) or higher. Conclusions: Ifosfamide plus paclitaxel is an active treatment regimen in advanced non-small-cell lung cancer, and compares favorabl y with the results of cisplatin-based chemotherapy. A phase II study i s in progress by the Cancer and Leukemia Group B, in an effort to bett er characterize the tolerance of the regimen, as well as its effect on tumor response and survival.