Hedy Lee Kindler, MD

Malignant mesothelioma is a devastating disease with an onset 20to 60 years after exposure to asbestos. Although most cytotoxic agentshave been evaluated for the treatment of mesothelioma, few single agentshave consistently yielded response rates above 20%. Antimetabolitesare the most active drugs against mesothelioma, and of these, theantifolate group is the most widely studied and effective. Pemetrexed(Alimta), a new antifolate, may be more active because of its differentmechanism of action. Several clinical trials have evaluated pemetrexedalone and in combination with a platinum agent for patients with malignantmesothelioma. A pivotal phase III trial has demonstrated thatcombination chemotherapy with pemetrexed and cisplatin improvessurvival, response rate, pulmonary function, and quality of life comparedwith single-agent cisplatin. Additional trials are evaluatingpemetrexed in the neoadjuvant setting and in combination with othercytotoxic and targeted agents.