Targeting thymidylate synthase in colorectal cancer: Critical re-evaluation and emerging therapeutic role of raltitrexed

Research output: Contribution to journalArticle

Abstract

Introduction: 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. Areas covered: 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. Expert opinion: 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.

Original languageEnglish
Pages (from-to)113-129
Number of pages17
JournalExpert Opinion on Drug Safety
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2014

Keywords

  • 5-fluorouracil
  • Cardiotoxicity
  • Colorectal cancer
  • Fluoropyrimidines
  • Folinic acid
  • Raltitrexed
  • Thymidylate synthase

ASJC Scopus subject areas

  • Pharmacology (medical)

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