Phase I-II study of amrubicin and cisplatin in previously untreated patients with extensive stage small cell lung cancer (ED-SCLC) (final report)

Abstract

7206 Background: Amrubicin (AMR), a totally synthetic 9-amino-anthracycline, demonstrated excellent single agent activity for ED-SCLC (Yana et al., Proc. ASCO, 1998, abstr.#1734). The aim of this trial was to determine the maximum-tolerated doses (MTDs) of combination therapy of AMR with cisplatin (CDDP), in order to assess the efficacy for ED-SCLC, pharmacokinetics and safety at their recommended doses (RDs). Methods: Eligibility criteria was defined as patients having histologically or cytologically proven measurable ED-SCLC, no previous systemic therapy, an ECOG PS of 0–2, and adequate organ function. AMR was administered iv once a day from day 1 to day 3, as was CDDP on day 1. Treatment was repeated every 3 weeks. Results: Four patients were enrolled at the dose level 1 (AMR 40 mg/m2/day and CDDP 60 mg/m2) and 3 patients at level 2 (AMR 45 mg/m2/day and CDDP 60 mg/m2), respectively. Consequently, the MTDs and RDs were determined to be level 2 and level 1, respectively (Negoro et al., Proc. ASCO, 2003, abstr. #2608). Combination of CDDP did not alter the pharmacokinetics of AMR. 41 patients at RDs have been assessed for efficacy, and 36 patients achieved a response of more than the PR. The response rate was 87.8%. Median survival time (MST) was 14.1 months and one-year survival rate was 64.2% on December of 2003 (interim data). Major toxicity was hematological in nature and a grade 3/4 neutropenia and leukopenia occurred in 95.1% and 65.9%, respectively. Conclusion: The combination of AMR and CDDP has demonstrated an impressively high response rate of 87.8% and MST of 14.1 months in patients with previously untreated ED-SCLC. The most common adverse events observed were grade 3/4 neutoropenia and leukopenia. Results from the phase I-II trial are encouraging. We are presently preparing a phase III clinical trial to compare combination therapy of irinotecan with CDDP. No significant financial relationships to disclose.