Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial

Lancet Oncol. 2013 Sep;14(10):1020-6. doi: 10.1016/S1470-2045(13)70363-2. Epub 2013 Aug 13.

Abstract

Background: The primary analysis of the JGOG 3016 trial showed that a dose-dense paclitaxel and carboplatin regimen significantly improves progression-free and overall survival compared with the conventional regimen as first-line chemotherapy for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. We report the long-term follow-up results for survival.

Methods: This randomised controlled trial was done at 85 centres in Japan. Patients with stage II-IV ovarian cancer were randomly assigned to receive conventional treatment (carboplatin area under the curve [AUC] 6 mg/mL per min and paclitaxel 180 mg/m(2) on day 1) or dose-dense treatment (carboplatin AUC 6 mg/mL per min on day 1 and paclitaxel 80 mg/m(2) on days 1, 8, and 15). The treatments were repeated every 3 weeks for six cycles; responding patients had three additional cycles. The randomisation was done centrally by telephone or fax, stratified by residual disease, stage, and histological type. The primary endpoint was progression-free survival; overall survival was a secondary endpoint. Long-term information on adverse events was not collected. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00226915.

Findings: 637 patients were enrolled, of whom 631 were analysed (312 assigned to the dose-dense regimen, 319 to the conventional regimen). Median follow-up was 76·8 months (IQR 68·9-85·6). Median progression-free survival was significantly longer in the dose-dense treatment group than in the conventional treatment group (28·2 months [95% CI 22·3-33·8] vs 17·5 months [15·7-21·7]; hazard ratio [HR] 0·76, 95% CI 0·62-0·91; p=0·0037). Median overall survival was 100·5 months (95% CI 65·2-∞) in the dose-dense treatment group and 62·2 months (52·1-82·6) in the conventional treatment group (HR 0·79, 95% CI 0·63-0·99; p=0·039).

Interpretation: Dose-dense treatment offers better survival than conventional treatment and is a potential new standard of care for first-line chemotherapy for patients with advanced epithelial ovarian cancer.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Ovarian Epithelial
  • Disease-Free Survival
  • Fallopian Tube Neoplasms / drug therapy*
  • Fallopian Tube Neoplasms / mortality
  • Fallopian Tube Neoplasms / pathology
  • Female
  • Humans
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Paclitaxel / administration & dosage
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / mortality
  • Peritoneal Neoplasms / pathology
  • Proportional Hazards Models

Substances

  • Carboplatin
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT00226915