Journal of Clinical Oncology. 2008 Jul 20;26(21):3567-72. [Link]
Simon GR, Verschraegen CF, JÃ¤nne PA, Langer CJ, Dowlati A, Gadgeel SM, Kelly K, Kalemkerian GP, Traynor AM, Peng G, Gill J, Obasaju CK, Kindler HL.
Thoracic Oncology Program and Experimental Therapeutics Program, H. Lee Moffitt Cancer Center and Research Institute, MRC-4W, 12902 Magnolia Drive, Tampa, FL 33612-9497, USA. email@example.com
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-naÃ¯ve 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.