Phase I trial of gemcitabine, administered as a standard and constant dose-rate infusion, in combination with paclitaxel in patients with advanced solid tumors (LOA-2).

The major purposes of this study were to determine the maximally tolerated dose (MTD), dose-limiting toxicity (DLT), toxicity profile, and antitumor activity of gemcitabine and paclitaxel combination therapy when administered to patients with advanced solid tumors, using two infusion schedules of each agent. Paclitaxel was administered on day 1, followed by gemcitabine, and gemcitabine alone was administered on day 8, of each 21-day treatment course. In the initial phase of the trial, paclitaxel was administered during 3 hours and gemcitabine during 30 minutes (schedule A). After the MTD was determined on this schedule, patients were then treated with paclitaxel during 1 hour and gemcitabine at a fixed dose-rate of 10 mg/m 2 /min (schedule B). Forty-six patients were treated with 176 courses at 7 dose levels. The MTD for schedule A was 1,300 mg/m 2 and 200 mg/m 2 and for schedule B was 1,000 mg/m 2 and 200 mg/m 2 for gemcitabine and paclitaxel, respectively. The DLT for schedule A was neutropenia and for schedule B was neutropenia and thrombocytopenia. Nonhematologic toxicity was relatively mild. Gemcitabine and paclitaxel, using both schedules of administration in the current trial, is a promising chemotheraneutic regimen.