Raltitrexed is a
cytotoxic agent, rationally designed to inhibit a specific molecular target,
thymidylate synthase. In contrast to other agents,
raltitrexed inhibits
thymidylate synthase directly and specifically in a mixed, noncompetitive manner, which may lead to an improved toxicity profile. After promising Phase II trials exploring the activity of
raltitrexed either as a single agent or in combination with a
platinum agent, a Phase III randomized study demonstrated that the combination of
raltitrexed and
cisplatin improves overall survival in
malignant pleural mesothelioma (MPM) and is superior compared with
cisplatin alone, without harmful effect on health-related quality of life. Moreover, the cost-effectiveness analysis found
raltitrexed plus
cisplatin to be cost effective compared with
cisplatin and compared with active supportive care. Based on these results,
raltitrexed is registered for the treatment of MPM in several European countries. MPM is hard to treat and has a poor prognosis. New treatment options, such as a combination of
cisplatin and
raltitrexed, which improve patient outcomes with no detrimental effect on quality of life, are a welcome addition to our therapeutic portfolio.