Chemotherapy and targeted therapies for unresectable malignant mesothelioma.

The global burden of mesothelioma is expected to increase in the coming decades. As a result the development of more effective therapies with an emphasis on personalized treatments based on validated prognostic and predictive biomarkers is an essential requirement. Progress has been made in the last decade with the development of newer generation anti-folates leading to the current standard of care of pemetrexed and cisplatin in patients with unresectable disease. However, the median overall survival of patients with this combination treatment is only 12 months. There is no consensus regarding second line therapy for patients who have progressed or not responded to pemetrexed based therapies although gemcitabine in combination with a platinum compound or single agent vinorelbine is a reasonable option. The development of effective targeted agents that are active in mesothelioma has to date been disappointing. Strategies involving the addition of bevacizumab to pemetrexed and cisplatin in the frontline setting, the histone deacetylase inhibitor vorinostat as second line therapy and studies evaluating the utility of maintenance therapy in mesothelioma are all ongoing and appear promising. In addition clinical trials investigating immunotherapy and gene therapy in combination with chemotherapy could potentially improve the prognosis of patients with mesothelioma.