The treatment of diffuse malignant pleural mesothelioma (MPM) is currently less than satisfactory. Survival statistics are best for the epithelial subtype and for tumors that can be completely removed by surgery. Radiotherapy provides no survival benefit and is used only to palliate symptoms or to prevent growth along needle tracks and incisions. The response to chemotherapeutic agents is poor, and to date there is no standard cytotoxic treatment. Antimetabolites may have some activity, and one trial of high-dose methotrexate has suggested a moderate response rate. There is also no evidence that any chemotherapy regimen given as a part of multimodality treatment, including radiotherapy and surgery, can improve survival. Recently, a renewed interest in MPM led to clinical trials with promising preliminary results for several agents alone or in combination, including gemcitabine, raltitrexed, vinorelbine, and pemetrexed. Pemetrexed, a folate-based inhibitor of thymidylate synthase and other enzymes, is currently under investigation in multiple malignancies. A phase I study of pemetrexed in combination with cisplatin showed a remarkable response rate of approximately 50% in patients with the epithelial subtype of MPM. This led to a large international study of the combination of pemetrexed plus cisplatin.
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