A phase I/II trial of combination paclitaxel and carboplatin in advanced or metastatic non-small cell lung cancer: preliminary results of an ongoing study.

Because of paclitaxel's (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) high single-agent activity in non-small cell lung cancer we developed a study to determine the maximum tolerated dose and a dose suitable for outpatient phase II/III trials of paclitaxel combined with a fixed dose of carboplatin (area under the concentration-time curve of 6, Calvert formula). From October 1993 to November 1994, 41 patients were entered into this trial, including six at dose level I (paclitaxel 150 mg/m2), six at dose level 2 (paclitaxel 175 mg/m2), II at dose level 3 (paclitaxel 200 mg/m2), 13 at dose level 4 (paclitaxel 225 mg/m2), and five at dose level 5 (paclitaxel 250 mg/m2). Patient characteristics included 27 men and 14 women with a median age of 64 years (age range, 46 to 81 years). The median Southwest Oncology Group performance status was I (range, 0 to 2). Nineteen patients had unresectable stage III and 22 had stage IV non-small cell lung cancer. Forty-one patients and 167 treatment courses were evaluable for toxicity. Hematologic toxicity was generally mild to moderate, not related to paclitaxel dose, and never dose limiting. Thrombocytopenia was remarkably mild, with only one episode of grade 3 toxicity (no grade 4). Arthralgias and cumulative sensory neuropathy were dose related and dose limiting. The maximum tolerated dose was defined at the 250 mg/m2 dose level with three of five patients achieving grade 3 (severe toxicity. The 225 mg/m2 dose level appears to be well tolerated, but accrual at this dose level is ongoing. This appears to be a highly active regimen, with objective responses in 20 (two complete responses and 18 partial responses) of 32 patients with objectively measurable disease for an overall response rate of 62.5%.