Emerging insights into the biology and therapy of malignant mesothelioma

Malignant mesothelioma is an aggressive malignancy that may be caused by environmental carcinogens (asbestos and erionite), viruses (SV40), and genetic predisposition. Pleural malignant mesotheliomas are far more common than the peritoneal variants. Diagnosis relies on radiographic studies as well as histology and molecular biologic analyses. The prognostic scoring systems of the Cancer and Leukemia Group B and the European Organization for Research and Treatment of Cancer are the most useful of those currently available. These systems rate performance status, age, histology, and hematologic parameters as the best prognostic factors for mesothelioma. Most patients with mesothelioma are not candidates for surgical or radiotherapy treatment, and cytotoxic agents are the only options. Historically, no classes or combinations of agents consistently yielded response rates over 20%. Recently, pemetrexed has been evaluated in phase I, II, and III clinical trials with promising results. The phase II trial showed an overall response rate of 14.1% with a 1-year survival rate of 47.8%. A phase III trial of cisplatin versus cisplatin and pemetrexed closed in February 2002 and a final analysis was presented in May 2002. Novel targeted agents are also being tested in clinical trials among mesothelioma patients and include drugs inhibiting the vascular endothelial growth factor and its receptor, the epidermal growth factor receptor, and platelet-derived growth factor receptor.