Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant epithelial ovarian and primary peritoneal cancers

Gynecol Oncol. 2006 Apr;101(1):126-31. doi: 10.1016/j.ygyno.2005.09.041. Epub 2005 Nov 3.

Abstract

Objectives: To evaluate the efficacy and tolerability of imatinib mesylate (Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) in patients with recurrent ovarian and primary peritoneal cancer.

Methods: This was an open-label, single-institution phase II trial. Patients were eligible if they had measurable platinum/taxane-resistant disease, received 2-4 prior treatment regimens, and over-expressed at least one imatinib target (c-Kit, PDGFR-beta, or c-Abl) by immunohistochemistry. Imatinib was administered orally at 600 mg daily for 6 weeks (one course) and was repeated in the absence of measurable progression.

Results: Sixteen enrolled patients were evaluable for toxicity and 12 for response. The median number of prior treatments was 4. A total of 29 courses were initiated. No complete or partial responses were documented during a median follow-up of 6.6 months. However, 4 (33%) of the 12 evaluable patients had stable disease lasting 3.8, 6.4, 7.5, and 8+ months. Expression of PDGFR-beta and c-Abl was seen in 15 (94%) and c-Kit in 8 (50%) patients' tumors. There was no relationship between best response (stable disease) and target expression. Adverse events were uncommon, with fatigue and nausea/vomiting being reported in 34% and 31% of cycles, respectively. Two patients underwent dose reduction for rash and edema (n = 1) and grade 3 neutropenia (n = 1). No grade 4 toxicity was observed.

Conclusion: Imatinib mesylate was well tolerated but did not produce clinical responses in patients with previously treated metastatic ovarian and primary peritoneal carcinoma.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Drug Resistance, Neoplasm
  • Fallopian Tube Neoplasms / drug therapy
  • Female
  • Humans
  • Imatinib Mesylate
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Organoplatinum Compounds / pharmacology
  • Ovarian Neoplasms / drug therapy*
  • Peritoneal Neoplasms / drug therapy*
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Taxoids / pharmacology

Substances

  • Antineoplastic Agents
  • Benzamides
  • Organoplatinum Compounds
  • Piperazines
  • Pyrimidines
  • Taxoids
  • Imatinib Mesylate