Pemetrexed in the treatment of malignant pleural mesotheliomaAuthor(s): Michael D Peake
Malignant pleural mesothelioma is a relatively uncommon cancer, but is increasing in frequency and will pose a major clinical challenge worldwide in the coming years. It has been considered a relatively chemoinsensitive tumor, and single-agent chemotherapy studies have been disappointing. However, pemetrexed, a pyrimidine-based multitargeted antifolate agent, has shown significant activity, and in the only Phase III study comparing two chemotherapy regimes (the EMPHACIS study), it has been demonstrated that the combination of pemetrexed and cisplatin with cisplatin alone led to an overall survival benefit of almost 3 months in the combination treatment arm, with parallel improvements in quality of life, symptom scores and pulmonary function. The combination of pemetrexed with cisplatin is the only regime licensed for use in malignant pleural mesothelioma in most parts of the world. Pretreatment with folic acid and vitamin B12 is required to minimize toxicity, but the regimen is generally well-tolerated in patients with a good performance status. It is now considered the ‘reference’ regime against which future chemotherapeutic approaches should be compared.