title: Raltitrexed in mesothelioma.
abstract: 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.
authors: Ghent University Hospital, Department of Respiratory Medicine/Thoracic Oncology, De Pintelaan 185, 9000 Ghent, Belgium.
authors: Veerle F
authors: VF
authors: Surmont
authors: Jan P
authors: JP
authors: van Meerbeeck
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy* / Q000378:metabolism; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D013876:Thiophenes; D013940:Thymidylate Synthase; C068874:raltitrexed; D002945:Cisplatin