A phase I study of topotecan plus carboplatin for relapsed SCLC: WJTOG trial

Abstract

A phase I study on relapsed small cell lung cancer (SCLC) was conducted to establish the toxicity and maximum tolerated dose of carboplatin with topotecan, and to observe the antitumor activity. Methods: Thirty-two SCLC patients who had received one previous line of chemotherapy were enrolled. Topotecan was infused for 30 minutes on days 1 to 5, and carboplatin for 60 minutes after the topotecan infusion on day 5 every 3 weeks. Granulocyte colonystimulating factor prophylaxis was administered from day 8 to white blood cell or neutrophil recovery. Results: The most frequent toxicities were neutropenia and thrombocytopenia. Nonhematological toxicities were generally mild. Three of six patients experienced a dose-limiting toxicity, thrombocytopenia, at dose level 6: 0.85 mg/m2 topotecan with area under curve 5 carboplatin (maximum tolerated dose). Of 29 evaluable patients, 5 (17.2%) had partial responses. Of 21 patients who relapsed more than 90 days after completion of first-line chemotherapy, 5 (23.8%) had partial responses. Median overall survival time and 1-year survival rate were 11.3 months and 50.0%, respectively. Conclusions: The recommended dose for further studies is 0.75 mg/m2 of topotecan on days 1 to 5 with area under curve 5 of carboplatin on day 5 every 3 weeks. This combination is well tolerated, and is promising for sensitive relapsed SCLC. A comparative study against single-agent topotecan for sensitive relapsed SCLC is warranted. © 2009 by the International Association for the Study of Lung Cancer.