Cisplatin, etoposide, and paclitaxel in the treatment of patients with extensive small-cell lung carcinoma

Purpose: The combination of cisplatin, etoposide, and paclitaxel was studie d in patients with extensive small-cell lung cancer in a phase I component followed by a phase II trial to determine the maximum-tolerated dose (MTD), characterize toxicity, and estimate response and median survival rates. Patients and Methods: Forty-one patients were treated between October 1993 and April 1997. Doses for the initial cohort were cisplatin 75 mg/m(2) on d ay 1, etoposide 80 mg/m(2)/d on days 1 to 3, and paclitaxel 130 mg/m(2) on day 1 over 3 hours. Cycles were repeated every 3 weeks for up to six cycles . The MTD was reached in the first six patients. In these six patients and in the next 35 patients, who were entered onto the phase II trial, response and survival were estimated. Results: Al the initial dose level, one of six patients developed febrile n eutropenia, and five of six achieved targeted neutropenia (nadir absolute g ranulocyte count, 100 to 1,000/1 mu L) without any other dose-limiting toxi city, defining this level as the MTD. Grade 4 neutropenia was observed in 8 8 (47%) of 188 total courses administered at or less than the MTD. Neutrope nia wets associated with fever in only 17 (9%) of 188 courses, but two pati ents experienced neutropenic sepsis that was fatal. Nonhematologic toxicity greater than grade 2 was observed in 10 (5%) of 188 total courses, with fa tigue, peripheral neuropathy, and nausea/vomiting most common. The overall objective response rate was 90% of 38 assessable patients: six complete res ponses (16%) and 28 partial responses (74%). Median progression-free and ov erall survival durations were 31 and 47 weeks, respectively. Conclusion: The combination of cisplatin, etoposide, and paclitaxel produce d response and survival rates similar to those of other combinations and wa s well tolerated.