A phase I trial of oxaliplatin and topotecan in recurrent ovarian carcinoma

Gynecol Oncol. 2007 Feb;104(2):422-7. doi: 10.1016/j.ygyno.2006.08.011. Epub 2006 Sep 22.


Objective: Oxaliplatin and topotecan have demonstrated activity as single agents against recurrent platinum-sensitive and -resistant ovarian cancer, as well as synergy in vitro. This was a dose-finding study of combination therapy with weekly topotecan and alternating-week oxaliplatin in patients with recurrent epithelial ovarian cancer.

Methods: Eligible patients had a diagnosis of recurrent ovarian or primary peritoneal carcinoma, a performance status of 0-2, and normal bone marrow, renal, and hepatic function. On days 1 and 15 of a 28-day cycle, patients received a fixed dose of oxaliplatin (85 mg/m2) via intravenous infusion. On days 1, 8, and 15, patients received an escalating dose of intravenous topotecan (2.0-4.0 mg/m2). Five dose levels were planned with a minimum cohort of 3 patients at each level.

Results: Thirteen patients were enrolled and received a total of 50 cycles of chemotherapy. The maximum tolerated dose was 85 mg/m2 of oxaliplatin and 3.0 mg/m2 of topotecan, and grade 3 neutropenia was the dose-limiting toxicity. Four of nine (44%) evaluable patients had stable disease or a partial response to the drug combination as assessed by cancer antigen-125 levels.

Conclusions: A 28-day schedule of oxaliplatin and topotecan is safe and well tolerated. Because of the in vitro synergy observed between topoisomerase I inhibitors and platinum derivatives and the tolerability reported in the current study, this regimen warrants further investigation.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Synergism
  • Female
  • Humans
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Oxaliplatin
  • Topotecan / administration & dosage
  • Topotecan / adverse effects


  • Organoplatinum Compounds
  • Oxaliplatin
  • Topotecan