Abstract
Malignant pleural mesothelioma (MPM) is most often caused by environmental and occupational exposure to durable mineral fibres including asbestos and the zeolite erionite. In Turkey, MPM due to environmental exposure to erionite is a serious public health problem in rural parts of Anatolia where there is also some evidence of genetic predisposition in some families.Although much is already known of MPM aetiology, therapeutic efforts remain poor and neither chemotherapy nor surgery have been shown to prolong survival significantly. Radiation therapy assists in reducing tumour growth and temporarily relieving pain, but does not extend the overall survival time. Single agent chemotherapy has shown a response rate of 10–33% not improved by combination chemotherapy. New agents including the anti-metabolites gemcitabine and specifically antifolates such as pemetrexed and raltitrexed seem more promising with response rates up to 48%, when combined with platinum compounds. The best characterised new agent is pemetrexed (LY 231514, ALIMTA) which inhibits the multiple folate-dependent enzymes thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotideformyltransferase (GARFT). A phase I combination study showed a response in 45% of patients and a large randomised single blind Phase III study was initiated in 1999. The pemetrexed/cisplatin combination significantly improved median survival when compared with cisplatin alone (12.1 months vs. 9.3 months) and was also significantly better in other efficacy parameters such as response rate, time to progressive disease, lung function and subjective indicators of quality of life. This combination should now be considered standard front-line therapy for patients with MPM.
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