Phase I study of combination chemotherapy with amrubicin and paclitaxel in relapsed small cell lung cancer

Abstract

18206 Background: Amrubicin (AMR) and paclitaxel (PTX) are promising agents for advanced non-small cell and small cell lung cancer (SC). However, the combination of these drugs for relapsed SC has never been reported. The aim of this study was to determine the maximum tolerated dose (MTD) of AMR and PTX, thus to investigate the recommended dose (RD) of this combination chemotherapy for relapsed SC patients. Methods: Relapsed SC patients after 1 or 2 regimens with age younger than 70 and good performance status (PS) were eligible. The treatment consisted of AMR (escalating from 30 to 40 mg/m2 by 5 mg/m2 increment) as a one- shot iv on days 1 through 3, and PTX (escalating from 70 to 90 mg/m2 by 10 mg/m2 increment) as a 60-minute infusion on days 4 and 11, repeated every 21 days. The dose-limiting toxicities (DLTs) were defined as grade 3/4 non-hematological toxicities, grade 4 thrombocytopenia, and grade 4 leukocytopenia / neutropenia for 4 days or more. Results: Nine relapsed SC patients were enrolled. All of them were sensitive-relapsed cases with mean age of 60.1 and PS of 0 - 1, and received one or more cycles of chemotherapy (mean: 2.7 cycles). Six patients were treated at level 1 (AMR 30mg/m2, PTX 70 mg/m2) with two of them on DLT of grade 4 neutropenia for 4 days or more. Three patients were treated at level 2 (AMR 35 mg/m2, PTX 70 mg/m2) with all of them on DLTs; grade 4 neutropenia for 4 days or more, grade 3 febrile neutropenia, and grade 3 pneumonia. Overall response rate was 63%. Conclusion: The MTD was identified to be level 2, and the RD for this regimen with AMR and PTX was considered to be 30 mg/m2 and 70 mg/m2, respectively. Treatment was well tolerated and the preliminary activity observed warrants further investigation. A phase II study is currently under investigation for relapsed and refractory SC patients. No significant financial relationships to disclose.