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 performedto determine the safety of the combination in patients with advanced lungcancer who had received no prior chemotherapy, and to identify a dose forphase II testing.Patients and methods: Patients with locally advanced or metastaticnon-small-cell lung cancer (NSCLC) or extensive small-cell lung cancer (SCLC),who had received no prior chemotherapy were treated with intravenouspaclitaxel given as a three hour infusion (starting dose 100mg/m²) and oral etoposide, 100 mg daily for five days. Twoschedules 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 hadSCLC. All patients were evaluable for toxicity. The maximum tolerated dose waspaclitaxel 200 mg/m² on day 1, in combination with oraletoposide 100 mg daily on days 1 to 5 (schedule A). The dose limitingtoxicities were mucositis, myalgia, diarrhoea, and paraesthesiae. Usingschedule B, myelosuppression, with febrile neutropenia was dose limiting ata paclitaxel dose of 160 mg/m². Amongst the 45 patients withNSCLC there were three complete and eight partial responses (24%;95% CI 13%–40%), while there was one completeresponse in the four patients with SCLC.Conclusion: Paclitaxel 200 mg/m² on day 1, with oraletoposide 100 mg daily on days 1 to 5 can be administered safely, and is therecommended dose for phase II studies.