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Pemetrexed Plus Gemcitabine As First-Line Chemotherapy for Patients With Peritoneal Mesothelioma: Final Report of a Phase II Trial

George R. Simon, Claire F. Verschraegen, Pasi A. Jänne, Corey J. Langer, Afshin Dowlati, Shirish M. Gadgeel, Karen Kelly, Gregory P. Kalemkerian, Anne M. Traynor, Guangbin Peng, John Gill, Coleman K. Obasaju, Hedy L. Kindler

From the H. Lee Moffitt Cancer Center, Tampa, FL; University of New Mexico, Albuquerque, NM; Dana-Farber Cancer Institute, Boston, MA; Fox Chase Cancer Center, Philadelphia, PA; Case Western Reserve University, Cleveland, OH; Wayne State University, Detroit, MI; University of Kansas Cancer Center, Kansas City, KS; University of Michigan Health System, Ann Arbor, MI; University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, WI; Eli Lilly & Co, Indianapolis, IN; and the University of Chicago, Chicago, IL

Corresponding author: George R. Simon, MD, Thoracic Oncology Program and Experimental Therapeutics Program, H. Lee Moffitt Cancer Center and Research Institute, MRC-4W, 12902 Magnolia Drive, Tampa, FL 33612-9497; e-mail: george.simon{at}moffitt.org

Purpose Pemetrexed in combination with cisplatin is approved for the treatment of pleural mesothelioma and is active in malignant peritoneal mesothelioma (MPeM). Pemetrexed and gemcitabine are synergistic in preclinical models, but the activity of this combination in MPeM is unknown. This clinical study assessed safety and efficacy of pemetrexed plus gemcitabine in chemotherapy-naïve patients with MPeM.

Patients and Methods Treatment consisted of gemcitabine 1,250 mg/m² on days 1 and 8, and pemetrexed 500 mg/m² on day 8, administered immediately before gemcitabine. Treatment was repeated every 21 days for six cycles or until disease progression. All patients received folic acid, vitamin B₁₂, and dexamethasone supplementation. End points included tumor response, toxicity, time to disease progression (TTPD), and overall survival (OS). Disease control rate (DCR) was also calculated.

Results Twenty patients were enrolled between December 2002 and May 2004. The confirmed response rate was 15% (95% CI, 3.2% to 37.9%), with three patients experiencing a partial response. The DCR was 50% (95% CI, 27.2% to 72.8%). The most common grade 3 to 4 nonhematologic toxicities included fatigue (20%), constipation (10%), vomiting (10%), and dehydration (10%). Hematologic toxicities included grade 3 to 4 neutropenia (60%) and febrile neutropenia (10%). One patient death was attributed to treatment. Median TTPD and OS times were 10.4 months and 26.8 months, respectively.

Conclusion The combination of pemetrexed plus gemcitabine was active in patients with MPeM with a notably high incidence of neutropenia. Median TTPD and OS seem promising. This regimen may provide an alternative to standard therapies, especially for patients who cannot tolerate a platinum-based regimen.

Supported by a grant from Eli Lilly & Co, Indianapolis, IN.

Presented at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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