Randomized phase II trial comparing amrubicin with re-challenge of platinum doublet in patients with sensitive-relapsed small-cell lung cancer: North Japan Lung Cancer Study Group trial 0702

Lung Cancer. 2015 Jul;89(1):61-5. doi: 10.1016/j.lungcan.2015.04.012. Epub 2015 May 4.

Abstract

Purpose: Amrubicin and re-challenge of platinum doublet are both effective treatments for sensitive-relapsed small-cell lung cancer (SCLC). However, no comparative study of these treatments has been reported. This randomized study was conducted to select the most suitable regimen for future evaluation.

Patients and methods: SCLC patients who had relapsed more than 90 days after their first-line platinum-doublet regimen were randomized to receive amrubicin (40mg/m(2), days 1-3) or re-challenge with platinum doublet. Primary endpoint was objective response rate (ORR), with secondary endpoints of progression-free survival (PFS), overall survival and toxicity profiles. We assumed that an ORR of 50% indicates potential usefulness, while that of 30% would constitute the lower limit of interest (alpha 0.1; beta 0.1). Initial estimated accrual was 28 patients to each arm.

Results: From February 2008 to June 2013, 60 patients were enrolled and 57 patients (27 amrubicin and 30 re-challenge) were found to be evaluable for efficacy and safety. The ORR and PFS were 67% (90% confidence interval, 52-82) and 5.4 months in the amrubicin group, and 43% (90% confidence interval, 28-58) and 5.1 months in the re-challenge group, respectively. Although grade 3 febrile neutropenia was observed in 19% of patients in the amrubicin group, these episodes were transient and manageable. Non-hematological toxicities were generally moderate and no treatment-related death was observed in either group.

Conclusion: Only amrubicin met the primary endpoint. Moreover, amrubicin demonstrated superior efficacy over re-challenge of platinum with acceptable levels of toxicity. Further evaluation of amrubicin for sensitive-relapsed SCLC is warranted.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anthracyclines / adverse effects
  • Anthracyclines / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Carboplatin / administration & dosage
  • Chemotherapy-Induced Febrile Neutropenia / etiology
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Irinotecan
  • Japan
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Retreatment
  • Small Cell Lung Carcinoma / drug therapy*
  • Survival Rate

Substances

  • Anthracyclines
  • Antineoplastic Agents
  • Etoposide
  • Irinotecan
  • amrubicin
  • Carboplatin
  • Cisplatin
  • Camptothecin