Phase II study of carboplatin and pemetrexed for the treatment of platinum-sensitive recurrent ovarian cancer

J Clin Oncol. 2008 Dec 10;26(35):5761-6. doi: 10.1200/JCO.2008.17.0282. Epub 2008 Nov 10.

Abstract

Purpose: More efficacious, less toxic combinations are needed to treat platinum-sensitive recurrent epithelial ovarian cancer (EOC). Pemetrexed is a multitargeted antifolate with manageable toxicity and has been combined with carboplatin to treat other cancers.

Patients and methods: This is a phase II study of carboplatin area under the curve 5 with pemetrexed 500 mg/m(2) administered intravenously on day 1 every 21 days for six cycles or for up to eight cycles if clinical benefit occurred. Eligible patients had platinum-sensitive recurrent EOC, peritoneal serous cancer, or fallopian tube cancer. The primary objective was to determine response rate defined by Response Evaluation Criteria in Solid Tumors; other end points included toxicities, progression-free survival (PFS), and overall survival (OS).

Results: Forty-five patients were accrued; 44 patients received treatment. Overall response rate was 51.1%; there were no complete responses (0%), 23 confirmed partial responses (51.1%), two unconfirmed partial responses (4.4%), 14 patients with stable disease (31.1%), and two patients with progressive disease after two cycles (4.4%). Grade 3 and 4 hematologic toxicities included neutropenia (41%), thrombocytopenia (23%), and anemia (9%); there were no episodes of febrile neutropenia. Grade 3 and 4 nonhematologic toxicities included fatigue (11%), nausea (5%), vomiting (5%), diarrhea (5%), syncope (5%), and pulmonary embolism (5%). Median PFS time was 7.57 months (95% CI, 6.44 to 10.18 months), mean OS time was 20.3 months, and median OS has not yet been reached with a mean follow-up time of 15.3 months.

Conclusion: Carboplatin/pemetrexed is a well-tolerated regimen with activity in platinum-sensitive recurrent EOC; further testing of this regimen in platinum-sensitive EOC patients is warranted.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Boston
  • Carboplatin / administration & dosage
  • Disease-Free Survival
  • Drug Administration Schedule
  • Fallopian Tube Neoplasms / drug therapy*
  • Fallopian Tube Neoplasms / mortality
  • Fallopian Tube Neoplasms / pathology
  • Female
  • Glutamates / administration & dosage
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • Humans
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Pemetrexed
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / mortality
  • Peritoneal Neoplasms / pathology
  • Time Factors
  • Treatment Outcome

Substances

  • Glutamates
  • Pemetrexed
  • Guanine
  • Carboplatin