Response to topotecan of symptomatic brain metastases of small-cell lung cancer also after whole-brain irradiation. a multicentre phase II study

Abstract

The purpose of this multicentre phase II study was to evaluate the efficacy and toxicity of topotecan in pretreated patients with small-cell lung cancer (SCLC) who relapsed with symptomatic brain metastases. 30 patients with a median age of 62 years were entered into the study. 22 patients received the initially planned dose of 1.5 mg/m(2) topotecan as a 30-min intravenous (i.v.) infusion for 5 consecutive days every 3 weeks. Due to the observed thrombocytopenia, the dose was reduced to 1.25 mg/m(2) in the last 8 patients. All 30 patients were pretreated with chemotherapy: 14 with one and 16 with at least two protocols. 8 patients had prior whole-brain iradiation (WBI): 7 in the prophylactic and 1 in the palliative setting. Concomitant systemic metastases were recorded in 24 patients at the time of brain relapse. Cerebral metastases responded in 33% of patients (10/30; three complete responses (CR) and seven partial responses (PR)). Noteworthy is the fact that response was achieved in 4 of 8 patients pretreated by WBI (3 in prophylactic and 1 in palliative setting). The systemic response rate was 29% (7/24). Median time to progression was 3.1 months (range 0.25-14.2+ months), median survival from the beginning of this study was 3.6 months (range 0.25-14.2+ months). Therapy was generally well tolerated, with myelotoxicity being the most common adverse event. Grade 3 leucocytopenia according to the Common Toxicity Criteria (CTC) occurred in 28% (23/83) of the courses and grade 4 in 22% (18/83). Grade 3 thrombocytopenia was observed in 17% of the courses (14/83) and grade 4 in 11% (9/83). 17% of patients (5/30) had a documented grade 3 infection. These results using topotecan are promising in heavily pretreated patients with SCLC brain metastases and merit further evaluation.