Methotrexate and gemcitabine combination chemotherapy for the treatment of malignant pleural mesothelioma

Kuribayashi,Kozo; Miyata,Shigeru; Fukuoka,Kazuya; Murakami,Aki; Yamada,Syusai; Tamura,Kunihiro; Hirayama,Noriko; Terada,Takayuki; Tabata,Chiharu; Fujimori,Yoshihiro; Nakano,Takashi

doi:10.3892/mco.2013.118

Methotrexate and gemcitabine combination chemotherapy for the treatment of malignant pleural mesothelioma

Authors:
- Kozo Kuribayashi
- Shigeru Miyata
- Kazuya Fukuoka
- Aki Murakami
- Syusai Yamada
- Kunihiro Tamura
- Noriko Hirayama
- Takayuki Terada
- Chiharu Tabata
- Yoshihiro Fujimori
- Takashi Nakano
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Affiliations: Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, Cancer Center, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Published online on: May 10, 2013 https://doi.org/10.3892/mco.2013.118
Pages: 639-642

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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/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 mg̸m2 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.

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