Phase I-II study of amrubicin and cisplatin in previously untreated patients with extensive-stage small-cell lung cancer

Abstract

Background: Amrubicin, a totally synthetic 9-amino-anthracycline, demonstrated excellent single-agent activity for extensive-stage small-cell lung cancer (ED-SCLC). The aims of this trial were to determine the maximum-tolerated doses (MTD) of combination therapy with amrubicin and cisplatin, and to assess the efficacy and safety at their recommended doses (RD). Patients and methods: Eligibility criteria were patients having histologically or cytologically proven measurable ED-SCLC, no previous systemic therapy, an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Amrubicin was administered on days 1-3 and cisplatin on day 1, every 3 weeks. Results: Four patients were enrolled at dose level 1 (amrubicin 40 mg/m2/day and cisplatin 60 mg/m2) and three patients at level 2 (amrubicin 45 mg/m2/day and cisplatin 60 mg/m2). Consequently, the MTD and RD were determined to be at level 2 and level 1, respectively. The response rate at the RD was 87.8% (36/41). The median survival time (MST) was 13.6 months and the 1-year survival rate was 56.1%. Grade 3/4 neutropenia and leukopenia occurred in 95.1% and 65.9% of patients, respectively. Conclusions: The combination of amrubicin and cisplatin has demonstrated an impressive response rate and MST in patients with previously untreated ED-SCLC. © 2005 European Society for Medical Oncology.