A phase I and pharmacological study of amrubicin and topotecan in patients of small-cell lung cancer with relapsed or extensive-disease small-cell lung cancer

Cisplatin-based chemotherapy is considered to be a standard treatment in patients with relapsed or extensive-disease (ED) small-cell. lung cancer (SCLC), the survival benefit remains modest. Relapsed or ED-SCLC patients were enrolled. Topotecan and amrubicin were administered on Days 1-5 and on Days 3-5, respectively. Nine patients received a total of 24 cycles. Since all. three patients experienced dose-limiting toxicity (grade 4 neutropenia lasting for more than 4 days, grade 3 febrile neutropenia, and grade 4 thrombocytopenia) at the third dose level (topotecan: 0.75 mg/m(2), amrubicin 40 mg/m(2)), the maximum tolerated dose was determined to be this dose level Objective response was observed in six patients (67%). The maximum concentration (C-max) and area under the plasma concentration-time curve (AUC) of amrubicin increased in a dose-dependent manner. Amrubicin did not influence the pharmacokinetics of topotecan. The Cm,, and AUC of amrubicin were correlated with the duration of grade 4 neutropenia. The mean C-max of topotecan on day 2 in responders (22.9 +/- 3.6) was significantly higher than that in non-responders (10.9 +/- 0.4). This phase I study showed the safety and activity of two-drug combination of amrubicin and topotecan in patients with relapsed or ED-SCLC. (C) 2006 Elsevier Ireland Ltd. All rights reserved.