A single-arm confirmatory study of amrubicin therapy in patients with refractory small-cell lung cancer: Japan Clinical Oncology Group Study (JCOG0901)

Objectives: We conducted an open-label, multicenter, single-arm study to confirm the efficacy and safety of amrubicin (AMR), a topoisomerase II inhibitor, for treating refractory small-cell lung cancer (SCLC). Patients and methods: Patients with chemotherapy-refractory SCLC received 40 mg/m(2) AMR for 3 consecutive days, every 21 days. The primary endpoint was the overall response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: Between November 2009 and February 2011, 82 patients were enrolled. Each patient received a median of four treatment cycles (range, 1-22 cycles). ORR was 32.9% [P < 0.0001 by the exact binomial test for the null hypothesis that ORR <= 10%; 95% confidence interval (CI), 22.9-44.2%] The median PFS and OS periods were 3.5 months (95% CI, 3.0-4.3 months) and 8.9 months (95% CI, 7.6-11.3 months), respectively. Significant differences in ORR (21.4% v 45.0%; P=0.034), PFS (median, 2.9 v 5.1 months; P= 0.0009), and OS (median, 7.9 v 13.1 months; P= 0.0128) were observed between patients previously treated with etoposide and others. Neutropenia was the most common grade 3 or 4 adverse events (93.9%), and febrile neutropenia developed in 26.8% patients. No treatment-related death occurred. Conclusions: AMR monotherapy can be considered an effective and safe treatment option for refractory SCLC. Previous chemotherapy with etoposide may influence AMR efficacy. (C) 2014 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.