Phase I/II trial of etoposide and carboplatin in extensive small-cell lung cancer. A report from the Cancer and Leukemia Group B.

Previously untreated extensive small-cell lung cancer (SCLC) patients with performance status 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and carboplatin doses of 50, 100, or 125 mg/m2/day on days 1-3 in a Phase I format. Among the ten eligible patients treated with 125 mg/m2/day of carboplatin, grade 3 or 4 infection occurred in six patients, grade 4 thrombocytopenia in four patients, and there was one death with myelosuppression. Thus, this dose was considered the maximum tolerated dose (MTD), and a Phase II trial was then conducted utilizing this treatment program. In the Phase II trials, 81% of the 48 eligible patients had grade 3 or 4 leukopenia, 76% had grade 3 or 4 thrombocytopenia, and 55% had grade 3 or 4 anemia. There were three (6%) toxic deaths from myelosuppression. The objective response rate was 63% (17% complete responders) with a median response duration of 6.2 months for complete responders and 6.4 months for partial responders. Median survival was 12 months. The MTD defined by this Phase I trial represents a 67-100% increase in etoposide and a 25% increase in carboplatin compared to prior studies. Cancer and Leukemia Group B (CALGB) plans to study further dose intensification of this regimen with colony-stimulating factors.