Abstract
7340 Background: Combination chemotherapy of topotecan and amrubicin for ED or relapsed SCLC has not been fully evaluated. To determine the maximum-tolerated dose (MTD), a Phase I study in patients with ED or relapsed SCLC was conducted. Methods: Both relapsed patients with prior chemotherapy and chemo-naïve ED patients were enrolled in this study. Topotecan was administered through days 1 to 5, whereas amrubicin was administered on days 3 to 5. Courses were repeated every 3 weeks. The starting doses of topotecan and amrubicin were 0.75 and 30 mg/m2/day, respectively. Blood samples were obtained during the second and third days of the first cycle. Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (Ver2.0). Results: Patients with ED or relapsed SCLC (n = 9) were enrolled between April and November 2003, including 3 sensitive-relapsed cases. A total of 24 courses were assessable for safety. The principle toxicity was myelosuppression. In the first course of dose level 3, DLT was observed in all 3 patients (persistence of grade 4 neutropenia in 1 patient, grade 3 thrombocytopenia with platelet transfusion in 1 patient, plus persistence of grade 4 neutropenia and leukopenia and grade 3 febrile neutropenia in 1 patient). Thus, MTDs of topotecan and amrubicin were determined to be 0.75 and 40 mg/m2, respectively. Objective response was obtained in 7 patients (78%), including 4 relapsed patients. Cmax and AUC of amrubicinol were correlated to duration of grade 4 neutropenia (Spearman’s test, p=0.0239 and 0.0211). Additionally, the mean Cmax of topotecan on day 2 in 7 responders was significantly higher than that in 2 non-responders (22.9±3.6 and 10.9±0.4, respectively, Mann-Whitney U test, p=0.0404). Conclusions: This combination was well tolerated and produced a promising antitumor effect for ED or relapsed SCLC. Several pharmacokinetic factors may be predictive of toxicity and response. No significant financial relationships to disclose.
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