Long-term results of a randomised phase III trial of weekly versus three-weekly paclitaxel/platinum induction therapy followed by standard or extended three-weekly paclitaxel/platinum in European patients with advanced epithelial ovarian cancer

Eur J Cancer. 2014 Oct;50(15):2592-601. doi: 10.1016/j.ejca.2014.07.015. Epub 2014 Aug 2.

Abstract

Background: Weekly paclitaxel/carboplatin might improve survival in platinum-resistant epithelial ovarian cancer (EOC). We compared efficacy of first-line weekly to three-weekly paclitaxel/cis- or carboplatin (PCw and PC3w) induction therapy, followed by either three or six PC3w cycles.

Patients and methods: In this multicentre, randomised phase III trial with 2×2 design, patients with FIGO stage IIb-IV EOC were randomised to six cycles PCw (paclitaxel 90mg/m(2), cisplatin 70mg/m(2) or carboplatin AUC 4) or three cycles PC3w (paclitaxel 175mg/m(2), cisplatin 75mg/m(2) or carboplatin AUC 6), followed by either three or six cycles PC3w. Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints were response rate (RR) and toxicity.

Results: Of 267 eligible patients, 133 received PCw and 134 PC3w. The first 105 patients received cisplatin, after protocol amendment the subsequent 162 patients received carboplatin. Weekly cisplatin was less well tolerated than weekly carboplatin. All PC3w cycles were well tolerated. At the end of all treatments, RR was 90.8% with no differences between the treatment arms. After a follow-up of median 10.3years (range 7.1-14.8), median PFS was 18.5 (95% confidence interval (CI) 15.9-21.0) months for PCw and 16.4 (95% CI 13.5-19.2) months for PC3w (p=0.78). Median OS was 44.8 (95% CI 33.1-56.5) months for PCw and 41.1 (95% CI 34.4-47.7) months for PC3w (p=0.98).

Conclusions: There was no benefit in terms of OS, PFS or RR for a weekly regimen nor for extended chemotherapy as first-line treatment for EOC in European patients.

Keywords: Carboplatin; Cisplatin; Dose-dense; Epithelial ovarian cancer; First-line; Paclitaxel; Weekly.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Disease-Free Survival
  • Drug Administration Schedule
  • Europe
  • Fatigue / chemically induced
  • Female
  • Follow-Up Studies
  • Humans
  • Induction Chemotherapy
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / pathology
  • Neutropenia / chemically induced
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Time Factors
  • Treatment Outcome
  • Vomiting / chemically induced
  • Young Adult

Substances

  • Carboplatin
  • Paclitaxel
  • Cisplatin