title: Methotrexate and gemcitabine combination chemotherapy for the treatment of malignant pleural mesothelioma.
abstract: 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/m2methotrexate and, 30 min later, a 30-min infusion of 800 mg/m2gemcitabine. Twenty-four hours following the administration of methotrexate, leucovorin rescue therapy was initiated (10 mg/m2leucovorin 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.
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan ;
authors.forename: Kozo
authors.initials: K
authors.lastname: Kuribayashi
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan ;
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyata
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan ;
authors.forename: Kazuya
authors.initials: K
authors.lastname: Fukuoka
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan ;
authors.forename: Aki
authors.initials: A
authors.lastname: Murakami
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan ;
authors.forename: Syusai
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan ;
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan ;
authors.forename: Noriko
authors.initials: N
authors.lastname: Hirayama
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan ;
authors.forename: Takayuki
authors.initials: T
authors.lastname: Terada
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan ;
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tabata
authors.affiliation: Cancer Center, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimori
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nishinomiya, Hyogo 663-8501, Japan ; ; Cancer Center, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
keywords: chemotherapy; gemcitabine; malignant mesothelioma; methotrexate