A dose escalating study of topotecan preceding cisplatin in previously untreated patients with small-cell lung cancer

Background: The aim was to define the MTD of topotecan (TPT) given before c isplatin in patients with previously untreated SCLC. Patients and methods: Alternating cycles A and B to a total of 6 cycles wer e given. Cycle A: TPT days 1-5 and cisplatin (50 mg/m(2)) day 5. Cycle B co nsisted of teniposide, carboplatin, vincristine, and cisplatin. TPT was esc alated at doses 0.75, 1.0, 1.25, and 1.5 mg/m(2). DLT was defined for the f irst cycle as grade 4 neutropenia with fever or when lasting >7 days, or gr ade 4 thrombocytopenia. Results: Fifteen patients with limited disease and six patients with extens ive disease were included. No episodes of DLT were recorded in the first cy cles A and consequently 1.5 mg/m(2) was defined as MTD. At 1.5 mg/m(2) (11 patients, 30 cycles), four and three episodes of grade 4 thrombocytopenia a nd neutropenia lasting more than seven days occurred in subsequent cycles A . Thrombocytopenia and anaemia were cumulative as more cycles were administ rated. Non-hematological toxicity was mild. The response rate was 86% (95% confidence interval (95% CI): 64%-97%) with 33% (95% CI: 15%-57%) achieving CR. Conclusions: 1.5 mg/m(2) TPT can be delivered safely with 50 mg/m(2) cispla tin on day 5 in patients with previously untreated SCLC.