The potential role of pemetrexed in gastrointestinal cancer

In 2004, the new-generation multitargeted antifolate pemetrexed was approved by the US Food and Drug Administration for the treatment of malignant pleural mesothelioma and as second-line monochemotherapy for advanced non-small cell lung cancer. However, pemetrexed as a single agent showed activity in preclinical and clinical studies, as well as in many other neoplasms such as gastrointestinal tumors, breast, head and neck, bladder and cervix cancer. Its tolerability profile is very favorable since the introduction of oral folic acid and vitamin B(12) supplementation in December 1999, and therefore, the maximum tolerated dose as single agent is probably higher than the dose actually utilized in clinical practice. Gastrointestinal tumors are the most common malignancies in the world, accounting for more than 25% of all cancers. In phase II studies exploring this multitargeted antifolate in advanced gastrointestinal tumors, pemetrexed showed an interesting degree of clinical activity, encouraging further trials evaluating the synergism with other drugs such as oxaliplatin, irinotecan and gemcitabine.