Preliminary results of a phase I study of weekly paclitaxel infusion in patients with non-small cell lung cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has a broad spectrum of activity, but the optimal schedule has not yet been determined. As a phase-specific agent, more frequent administration theoretically may be more effective. We have previously demonstrated that a weekly schedule of paclitaxel used as a radiation sensitizer is well tolerated by outpatients. We therefore conducted a phase I study of weekly paclitaxel in patients with chemotherapy-naive metastatic non-small cell lung cancer to determine the maximum tolerated dose of this alternative schedule. In all, 26 patients were entered into this study through six paclitaxel dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk) administered weekly for 6 of 8 weeks. All patients had a performance status of 0 through 2, with a median age of 65 years (age range, 37 to 80 years). Sites of disease included lung, bone, liver, soft tissue, and brain. Of the 26 entered, 24 patients completed the first 8-week cycle and are evaluable for toxicity. Dose-limiting toxicity, which consisted of neutropenia, occurred in four of six patients at 200 mg/m2/wk and in two of six at 175 mg/m2/wk. Only one evaluable patient required admission for febrile neutropenia. Other toxicities included rash, pulmonary infiltrate, myalgia, neuropathy, and alopecia. Nine (38%) of the 24 patients demonstrated objective responses. One patient with stable disease completed 48 weeks of therapy. Others remain in active treatment. We conclude that the maximum tolerated dose of paclitaxel administered for 6 consecutive weeks of an 8-week cycle is 175 mg/m2/wk and is limited principally by neutropenia. The response rate with this schedule is encouraging and merits further investigation.