TY - JOUR
T1 - Targeting thymidylate synthase in colorectal cancer
T2 - Critical re-evaluation and emerging therapeutic role of raltitrexed
AU - Avallone, Antonio
AU - Gennaro, Elena Di
AU - Silvestro, Lucrezia
AU - Iaffaioli, Vincenzo Rosario
AU - Budillon, Alfredo
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - 5-fluorouracil
KW - Cardiotoxicity
KW - Colorectal cancer
KW - Fluoropyrimidines
KW - Folinic acid
KW - Raltitrexed
KW - Thymidylate synthase
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U2 - 10.1517/14740338.2014.845167
DO - 10.1517/14740338.2014.845167
M3 - Article
C2 - 24093908
AN - SCOPUS:84890534014
VL - 13
SP - 113
EP - 129
JO - Expert Opinion on Drug Safety
JF - Expert Opinion on Drug Safety
SN - 1474-0338
IS - 1
ER -