A randomized phase III study of single-agent amrubicin vs. carboplatin/etoposide in elderly patients with extensive-disease small-cell lung cancer

Clin Lung Cancer. 2014 Mar;15(2):96-102. doi: 10.1016/j.cllc.2013.11.006. Epub 2013 Nov 14.

Abstract

Introduction: The efficacy and safety of amrubicin, a third-generation synthetic anthracycline, were evaluated by comparison with carboplatin/etoposide combination therapy in elderly Japanese patients with extensive-disease small-cell lung cancer (ED-SCLC).

Patients and methods: Eligibility included histologically or cytologically proven SCLC, no previous systemic chemotherapy, performance status of 0 to 2, and age ≥ 70 years. Patients received amrubicin (70-74 years old, 40-45 mg/m(2); ≥ 75 years old, 40 mg/m(2)) intravenously on days 1 to 3 every 3 weeks for 4 to 6 cycles or carboplatin (area under the curve of 5 intravenously on day 1) and etoposide (80 mg/m(2) intravenously on days 1 to 3) every 3 weeks for 4 to 6 cycles.

Results: The target number of patients was 130 with 65 in each arm. However, the study was terminated early owing to 3 treatment-related deaths in the amrubicin arm, and only 62 patients (median age, 76 years; range, 70-88 years) were enrolled. The characteristics of the patients in the amrubicin and carboplatin/etoposide arms did not differ significantly. Overall survival, time to progression, and objective response rate were 10.9 vs. 11.3 months (P = .7353), 4.7 vs. 4.4 months, and 74.2% (23 of 31) vs. 60.0% (18 of 30), respectively, and quality of life showed no significant difference between the 2 arms. Higher incidences of febrile neutropenia and interstitial lung disease of grade 3 or worse occurred with amrubicin (34.4% vs. 3.3% and 12.5% vs. 0%, respectively).

Conclusion: These results indicate that amrubicin monotherapy at 40 to 45 mg/m(2) is toxic and intolerable in elderly Japanese patients with ED-SCLC.

Keywords: Chemotherapy; Interstitial lung disease; Pulmonary disease; Pulmonary toxicity; Treatment-related death.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anthracyclines / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary
  • Carboplatin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Neoplasm Staging
  • Prognosis
  • Quality of Life
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology
  • Survival Rate

Substances

  • Anthracyclines
  • Etoposide
  • amrubicin
  • Carboplatin