Phase I Study of Fludarabine and Paclitaxel for the Treatment of Low-Grade Non-Hodgkin's Lymphoma

We conducted a phase I clinical trial of a new combination of fludarabine and paclitaxel in which 19 patients with histologically confirmed recurrent low-grade non-Hodgkin's lymphoma (NHL) were treated at five dose levels. Fludarabine was administered intravenously by bolus for 5 days and paclitaxel was given by intravenous (IV) continuous infusion for 96 or 72 hours starting day 1. Courses were repeated every 4 weeks. Patients whose disease responded received a maximum of six courses. All 19 patients received at least one course and could be evaluated for toxic effects, and 18 patients could be evaluated for response. The maximum tolerated dose (MTD) was 20 mg/m2/day IV bolus for 5 days of fludarabine plus 60 mg/m2/day IV of paclitaxel given as a continuous infusion over 72 hours. The limiting toxic effect was neutropenic fever, which was observed in five of the seven patients treated at the highest dose level. Grade 3 non-hematologic toxic effects of stomatitis (14%), neuropathy (14%), and hypotension (...