A Phase I Study of Topotecan Plus Carboplatin for Relapsed SCLC: WJTOG Trial

Introduction: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 colony-stimulating 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.