A phase I trial of a 5-day schedule of intravenous topotecan and etoposidein previously untreated patients with small-cell lung cancer

A phase I dose-escalation study was undertaken to determine the maximum tol erated dose of the intravenous combination of topotecan and etoposide in pr eviously untreated patients with small-cell lung cancer. Nineteen patients were treated with 30-min infusions of topotecan (0.5 mg/m(2)/day for cohort 1; 0.75 mg/m(2)/day for cohort 2) followed by 1-hour infusions of a fixed daily dose of etoposide (60 mg/m(2)/day) for 5 consecutive days every 3 wee ks. Patient cohort 1 (n = 7) received a total of 41 courses of chemotherapy . Grade 4 neutropenia occurred after 17% of the courses of therapy, and the re was 1 episode of dose-limiting toxicity in this patient cohort. In patie nt cohort 2 (n = 12), a total of 64 courses of chemotherapy were administer ed. Grade 3 or 4 neutropenia occurred following 41 and 37% of the courses o f therapy, respectively. Grade 3 thrombocytopenia occurred following 19% of the courses of therapy, and there were 3 episodes of dose-limiting toxicit y in this patient cohort. There were no toxic deaths, and all non hematolog ic toxicity (except hair loss) was less than or equal to grade 2. No furthe r dose escalation was performed because of the degree of myelosuppression s een in patient cohort 2. All 19 patients were evaluable for response. Eight een (95%) patients responded (14 partial responses and 4 complete responses ) and the median survival was 10 months. This 5-day schedule of intravenous topotecan and etoposide administered sequentially on the same day is well tolerated, and the preliminary response rates were high in patients with pr eviously untreated small-cell lung cancer. Copyright (C) 2001 S. Karger AG, Basel.