Gastrointestinal Medical Oncology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - IRCCS , Via M. Semmola - 80131 Napoli , Italy +39 081 5903629 ; +39 081 5903813 ;
Expert Opin Drug Saf. 2014 Jan;13(1):113-29. doi: 10.1517/14740338.2014.845167. Epub 2013 Oct 5.
5-fluorouracil continues to be the cornerstone of treatment for colorectal cancer. Although fluoropyrimidines are generally considered as well-tolerated drugs, severe toxicities can be a major clinical problem, and the recommended prolonged infusion of 5-fluorouracil provokes discomfort in patients. Raltitrexed (Tomudex), a quinazoline analogue of folinic acid, is a selective and direct thymidylate synthase (TS) inhibitor with a convenient 3-weekly schedule of administration.
In this review, through critical insight into the mechanism of action and main clinical experiences, the authors suggest the necessity to reconsider raltitrexed as a valuable anticancer drug and as a suitable option for colorectal cancer. The authors highlight its emerging therapeutic role in clinical practice for patients with fluoropyrimidine-induced cardiotoxicity or a significant history of cardiac disease.
This review discusses if TS could still be a relevant target for colorectal cancer in the era of molecular therapy and if raltitrexed should still be considered a drug with a life-threatening toxicity. Furthermore, this review discusses the principal combination clinical experiences of raltitrexed and its emerging therapeutic role in clinical practice as a suitable option for colorectal cancer patients with fluoropyrimidine-induced cardiotoxicity or a significant history of cardiac disease.
5-氟尿嘧啶仍然是治疗结直肠癌的基石。虽然氟嘧啶类药物通常被认为是耐受性良好的药物，但严重的毒性可能是一个主要的临床问题，而推荐的 5-氟尿嘧啶延长输注会引起患者不适。雷替曲塞（Tomudex）是一种叶酸类似物喹唑啉，是一种选择性和直接的胸苷酸合成酶（TS）抑制剂，每周给药 3 次，使用方便。
在这篇综述中，通过对作用机制和主要临床经验的深入分析，作者提出有必要重新考虑雷替曲塞作为一种有价值的抗癌药物，以及作为结直肠癌的一种合适选择。作者强调了它在氟嘧啶引起的心脏毒性或有明显心脏病史的患者的临床实践中的新兴治疗作用。
这篇综述讨论了在分子治疗时代，TS 是否仍然是结直肠癌的一个相关靶点，以及雷替曲塞是否仍应被视为一种具有致命毒性的药物。此外，这篇综述还讨论了雷替曲塞的主要联合临床经验及其在临床实践中的新兴治疗作用，作为氟嘧啶引起的心脏毒性或有明显心脏病史的结直肠癌患者的合适选择。
