Phase I study of paclitaxel and oral etoposide in previously untreated non-small-cell and extensive small-cell lung cancer.

PURPOSE This phase I study of paclitaxel and oral etoposide was performed to determine the safety of the combination in patients with advanced lung cancer who had received no prior chemotherapy, and to identify a dose for phase II testing. PATIENTS AND METHODS Patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) or extensive small-cell lung cancer (SCLC), who had received no prior chemotherapy were treated with intravenous paclitaxel given as a three hour infusion (starting dose 100 mg/m2) and oral etoposide, 100 mg daily for five days. Two schedules of administration were used with the paclitaxel given on day 1 (schedule A) or day 5 (schedule B) of a 21 day cycle. RESULTS Forty-nine patients were entered on the study, four of whom had SCLC. All patients were evaluable for toxicity. The maximum tolerated dose was paclitaxel 200 mg/m2 on day 1, in combination with oral etoposide 100 mg daily on days 1 to 5 (schedule A). The dose limiting toxicities were mucositis, myalgia, diarrhoea, and paraesthesiae. Using schedule B, myelosuppression, with febrile neutropenia was dose limiting at a paclitaxel dose of 160 mg/m2. Amongst the 45 patients with NSCLC there were three complete and eight partial responses (24%; 95% CI 13% 40%), while there was one complete response in the four patients with SCLC. CONCLUSION Paclitaxel 200 mg/m2 on day 1, with oral etoposide 100 mg daily on days 1 to 5 can be administered safely, and is the recommended dose for phase II studies.