Molecular and Clinical Oncology. 2013 July.[Link]

Fujimori Y, Fukuoka K, Hirayama N, Kuribayashi K, Miyata S, Murakami A, Nakano T, Tabata C, Tamura K, Terada T, Yamada S.

Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan; Cancer Center, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Correspondence to: Dr Yoshihiro Fujimori, Cancer Center, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501


Malignant pleural mesothelioma (MPM) is an aggressive tumor of serosal surfaces with a poor prognosis. Methotrexate and gemcitabine have exhibited single-agent activity in MPM. We evaluated the feasibility of sequential administration of these agents in the treatment of MPM. A total of 21 patients with MPM received a 30-min infusion of 100 mg/m2 methotrexate and, 30 min later, a 30-min infusion of 800 mg/m2 gemcitabine. Twenty-four hours following the administration of methotrexate, leucovorin rescue therapy was initiated (10 mg/m2 leucovorin administered 4 times at 6-h intervals). These treatments were administered weekly, with 4 weekly administrations constituting a cycle of therapy. A total of 88 cycles were administered to the 21 patients, with each patient receiving 1–10 cycles (median, 4.2 cycles). Eight patients (38.1%) exhibited a partial response, 10 patients (47.6%) had stable disease and 3 patients (14.3%) had progressive disease. The median overall survival was 19.4 months (range, 02–41 months). One-year and 2-year survival rates were 61.9 and 38.1%, respectively. Hematological toxicity was considered acceptable, with grade 3–4 toxicities occurring in 3 (14.3%) patients. Non-hematologic toxicity was generally mild. There was no treatment-related mortality. Our results suggest that methotrexate and gemcitabine combination therapy is feasible and effective in the treatment of MPM. This regimen may offer an alternative to platinum-based chemotherapy and a prospective trial including a larger cohort of patients is recommended to confirm these results.