Multicenter randomized open-label phase III study comparing efficacy, safety, and tolerability of conventional carboplatin plus etoposide versus dose-intensified carboplatin plus etoposide plus lenograstim in small-cell lung cancer in "extensive disease" stage

Am J Clin Oncol. 2009 Feb;32(1):61-4. doi: 10.1097/COC.0b013e31817be954.

Abstract

Background: The combination of carboplatin and etoposide (CE) is one of the most effective regimens in the treatment of small-cell lung cancer (SCLC). The aim of this study was to investigate whether dose-intensified CE with the supplementation of granulocyte-colony-stimulating factor (G-CSF) is more effective than conventional CE in terms of survival with acceptable toxicity.

Methods: In a 2-arm multicentric prospective open label study, adult patients with SCLC in "extensive disease" stage were randomized either to conventional CE (carboplatin AUC 5 on day 1 IV and etoposide 140 mg/m IV on days 1-3, q28 days) or to dose-intensified therapy (carboplatin AUC 5 on day 1 IV and etoposide 190 mg/m days 1-3 IV with lenograstim 263 microg subcutaneously on days 4-13, q21 days). Primary end point was overall survival; secondary endpoints were toxicity, quality of life, and disease-free survival.

Results: Seventy-nine patients were included. Thirty-seven received conventional CE and 42 received the dose-intensified regimen. Median survival in the conventional group and the dose-intensified group were 11.2 months [confidence interval (CI) 9.1-15.2] and 11.7 months (CI 8.8-14.7), respectively. Progression-free survival was 6.7 (CI 5.8-7.5) and 7.4 months (CI 6.2-9.0), respectively. There was no statistically significant difference between these groups. Grade 3/4 neutropenia occurred in 69.4% in the conventional arm versus 37.5% in the dose-intensified group (P = 0.009).

Conclusion: Dose-intense CE with GM-CSF support can be administered safely but does not prolong overall or progression-free survival compared with standard therapy.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Drug Therapy, Combination
  • Etoposide / administration & dosage
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Lenograstim
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Quality of Life
  • Recombinant Proteins / therapeutic use
  • Safety
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / pathology
  • Survival Rate
  • Treatment Outcome
  • Young Adult

Substances

  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Etoposide
  • Lenograstim
  • Carboplatin