Phase I/II study of amrubicin and nedaplatin in patients with untreated, advanced, non-small cell lung cancer

A phase I/II study of combination chemotherapy with amrubicin and nedaplatin for patients with untreated, advanced, non-small cell lung cancer (NSCLC) was conducted. Amrubicin was given on days 1-3, with nedaplatin given on day 1. The treatment was repeated every 3 weeks. In the phase I trial, the initial amrubicin dose of 25 mg/m(2) was escalated in 5-mg/m(2) increments until the maximum tolerated dose was reached, with the dose of nedaplatin fixed at 100 mg/m(2). In the phase II trial, the primary endpoint was the overall response rate (ORR), assuming 20% for a standard therapy and 40% for a target therapy (α = 0.05 and β = 0.20), and the estimated required total number of patients was 35. In the phase I study, nedaplatin 100 mg/m(2) and amrubicin 25 mg/m(2) was recommended. In the phase II study, 17 out of 35 patients achieved a partial response, and the ORR was 48.6%. Grade 3/4 neutropenia, grade 3 anemia and grade 3/4 thrombocytopenia occurred in 62.9, 11.4 and 11.4% of cycles, respectively. Febrile neutropenia occurred in 5 cycles (3.9%) and all cases were manageable. The recommended dose of this combination is well tolerated and effective in patients with advanced NSCLC.