Phase II trial of amrubicin and carboplatin in patients with sensitive or refractory relapsed small-cell lung cancer

Amrubicin is a novel, totally synthesized anthracycline derivative, and has antitumor activity against several human tumor xenografts. The combination of amrubicin with platinum derivative showed additive effect against a human small-cell lung cancer (SCLC) cell line. Until now, the combination of amrubicin plus carboplatin has not been studied in patients with previously treated SCLC. Therefore, we examined the safety and efficacy of the combination of amrubicin plus carboplatin in patients with sensitive or refractory relapsed SCLC. Patients with previously treated SCLC were eligible if they had a performance status of 2 or less, were 75 years or younger, and had adequate organ function. Twenty-five patients were enrolled (21 men and 4 women; median age, 65 years; age range 55-73 years). Patients received the combination of amrubicin (30 mg/m² on days 1-3) plus carboplatin (with a target area under the concentration-versus-time curve of 4 mg min/ml using the Calvert formula on day 1) every 3 weeks. The overall response rate was 36.0% (95% confidence interval CI], 18.0-57.5%). Response rates differed significantly between patients with sensitive relapse (58.3%; 95% CI, 27.7-84.8%) and those with refractory relapse (15.4%; 95% CI, 1.9-15.4%; p = 0.03). The median survival time (MST) from the start of this treatment was 7 months (range: 1-42 months); the MST of patients with sensitive relapse (10 months) was significantly longer than that of patients with refractory relapse (5 months: p = 0.004). The median progression-free survival (PFS) time was 3 months (range: 1-14 months): the median PFS time of patients with sensitive relapse (5 months) was significantly longer than that of patients with refractory relapse (2 months; p = 0.01). The most frequent grade 3-4 toxicity was myelosuppression, especially neutropenia, which developed in 88% of patients. Grade 3-4 thrombocytopenia developed in 44% of patients, and anemia developed in 56%. Nonhematologic toxicities were generally mild to moderately severe and temporary. None of the patients had cardiotoxicity. In conclusion, this therapy is effective and well tolerated for previously treated SCLC.