Multi-institutional phase I/II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung carcinoma

Purpose: To determine the feasibility of adding paclitaxel to standard cisp latin/etoposide (EP) and thoracic radiotherapy. Patients and Methods: Thirty-one patients were enrolled onto this study. Du ring the phase I section of this study, the dose of paclitaxel was escalate d in groups of three or more patients. Cycles were repeated every 21 days. For cycles 1 and 2, paclitaxel was administered according to the dose-escal ation schema at doses of 100, 135, or 170 mg/m(2) intravenously over 3 hour s on day I. Once the maximum-tolerated dose (MTD) of paclitaxel (for cycles 1 and 2, concurrent with radiation) was determined, that dose was used in all subsequent patients entered onto the phase II section of this study, fo r cycles 3 and 4, the paclitaxel dose was fixed at 170 mg/m(2) in all patie nts. On day 2, cisplatin 60 mg/m(2) was administered for all cycles. On day s 1, 2, and 3, etoposide 60 mg/m(2)/d (cycles 1 and 2) or 80 mg/m(2)/d (cyc les 3 and 4) wets administered. Chest radiation was given at 9 Gy/wk in fiv e fractions for 5 weeks beginning on day 1 of cycle 1. Granulocyte colony-s timulating factors were used during cycles 3 and 4 only. Results: Twenty-eight patients were assessable. The MTD of paclitaxel war 1 35 mg/m(2), with the dose-limiting toxicity being grade 4 neutropenia. Cycl es 1 and 2 were associated with grade 4 neutropenia in 32% of courses, with fever occurring in 7% of courses and grade 2/3 esophagitis in 13%. Cycles 3 and 4 were complicated by grade 4 neutropenia in 20% of courses, with fev er occurring in 6% of courses and grade 2/3 esophagitis in 16%. The overall response rate war 96% (complete responses, 39%; partial responses, 57%). A fter a median follow-up period of 23 months (range, 9 to 40 months), the me dian survival time was 22.3 months (95% confidence interval, 15.1 to 34.3 m onths). Conclusion: The MTD of paclitaxel with radiation and EP treatment is 135 mg /m(2) given over 3 hours. In this schedule of administration, a high respon se rate and acceptable toxicity can be anticipated. J Clin Oncol 18:1102-11 09. (C) 2000 by American Society of Clinical Oncology.