Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: final report of a phase II trial.

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/m(2) on days 1 and 8, and pemetrexed 500 mg/m(2) 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 B(12), 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.