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 40mg/m² 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.