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

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.

• Authors: Ursula A Matulonis, Neil S Horowitz, Susana M Campos, Hang Lee, Julie Lee, Carolyn N Krasner, Suzanne Berlin, Maria R Roche, Linda R Duska, Lauren Pereira, Deborah Kendall, Richard T Penson
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 35 Pg. 5761-6 (Dec 10 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 19001330 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamates
• Pemetrexed
• Guanine
• Carboplatin

Topics

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