Randomized phase II trial of weekly dose-intensive chemotherapy or amrubicin plus cisplatin chemotherapy following induction chemoradiotherapy for limited-disease small cell lung cancer (JCOG1011)

Lung Cancer. 2017 Jun:108:232-237. doi: 10.1016/j.lungcan.2017.04.002. Epub 2017 Apr 4.

Abstract

Objectives: The objective of this study was to select, for a phase III trial, the more promising of weekly-dose intensive chemotherapy or amrubicin+cisplatin chemotherapy as subsequent therapy after induction chemoradiotherapy for previously untreated limited-disease small cell lung cancer (LD-SCLC).

Materials and methods: Patients aged 20-70 years with untreated clinical stage II/III LD-SCLC were eligible. After one cycle of accelerated hyperfractionation thoracic radiotherapy with etoposide plus cisplatin, patients without progression were randomized to either 3 cycles of cisplatin 25mg/m2 (days 1, 8), doxorubicin 40mg/m2 (day 1), etoposide 80mg/m2 (days 1-3), and vincristine 1mg/m2 (day 8) every 2 weeks (CODE) or amrubicin 40mg/m2 (days 1-3) and cisplatin 60mg/m2 (day 1) every 3 weeks (AP). The primary endpoint was the one-year progression-free survival (PFS). The sample size was 72 to select the arm yielding a better one-year PFS (55% vs. 65%) with a probability of 80%.

Results: From March 2011 to February 2014, 85 patients were registered. After the induction chemoradiotherapy, 75 patients were randomized to CODE (n=39) or AP (n=36). The one-year PFS (95% confidence interval) was 41.0% (25.7-55.8) in the CODE group and 54.3% (36.6-69.0) in the AP group. Grade 4 neutropenia/grade 3 febrile neutropenia occurred in 47%/16% in the CODE group and 78%/42% in the AP group.

Conclusion: The one-year PFS was better in the AP group, but it did not reach the expected 55%. Therefore, neither regimen is suitable for a phase III trial.

Keywords: Cisplatin; Limited disease; Small cell lung cancer; Weekly chemotherapy; amrubicin.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemoradiotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Disease Management
  • Drug Administration Schedule
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Remission Induction
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology*
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Anthracyclines
  • amrubicin
  • Cisplatin