Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group

J Clin Oncol. 2008 Jul 1;26(19):3176-82. doi: 10.1200/JCO.2007.15.1258.

Abstract

Purpose: The management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine.

Patients and methods: Women with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m(2)/d, topotecan 1.0 mg/m(2) plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m(2)/d plus gemcitabine 800 mg/m(2) on day 1 and 600 mg/m(2) on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire).

Results: The trial enrolled 502 patients with a mean age of 60.5 years (+/- 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia.

Conclusion: Nonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chi-Square Distribution
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Etoposide / administration & dosage
  • Female
  • Gemcitabine
  • Germany
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Ovarian Neoplasms / drug therapy*
  • Proportional Hazards Models
  • Quality of Life
  • Survival Rate
  • Topotecan / administration & dosage*
  • Treatment Outcome

Substances

  • Deoxycytidine
  • Etoposide
  • Topotecan
  • Gemcitabine