Combination of weekly topotecan and gemcitabine as a salvage treatment in patients with recurrent ovarian cancer: a phase I study

Minerva Ginecol. 2019 Jun;71(3):182-190. doi: 10.23736/S0026-4784.19.04249-7. Epub 2019 Feb 6.

Abstract

Background: Evaluation of safety of the weekly intravenous gemcitabine/topotecan combination as salvage treatment in patients with recurrent epithelial ovarian cancer.

Methods: Twenty-four women with histologically-proven relapsed ovarian cancer (ROC) were enrolled in the study. Topotecan (1.75 mg/m2 IV) along with escalated doses of gemcitabine (starting dose 700 mg/m2 with increments of 100 mg/m2) were administered on days 1, 8, and 15 every 28 days. The maximum tolerated dose (MTD) and the dose-limiting toxicity of the combination were evaluated at the first cycle.

Results: Twenty-four ROC patients were enrolled in six dose-levels. Most patients had high-grade serous metastatic ovarian cancer (41.7%) and performance status score of 0-1 (95.8%). For 12 patients (50%) treatment was 2nd line and for 12 >2nd line. Eighty-eight cycles were administered with a median of three cycles per patient. The MTD was not reached and grade 3-4 (3.4% and 2.3% of cycles, respectively) neutropenia and grade 4 (3.4% of cycles) thrombocytopenia were the main adverse events. There was no case of febrile neutropenia. Non-hematologic toxicity was mild with grade 2 fatigue being the most frequent complain. The recommended MTD doses of the combination were topotecan 1.75 mg/m2 and gemcitabine 1200 mg/m2 on days 1, 8, and 15 every 28 days. Two complete (8.3%) and three (12.5%) partial responses were achieved (ORR: 20.8%).

Conclusions: The weekly administration of gemcitabine/topotecan regimen in patients with pretreated metastatic ovarian cancer is an active chemotherapy combination, even in heavily pretreated patients, with a manageable toxicity profile which merits further investigation.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Gemcitabine
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Ovarian Neoplasms / drug therapy*
  • Salvage Therapy / methods
  • Topotecan / administration & dosage*

Substances

  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • Deoxycytidine
  • Topotecan
  • Gemcitabine