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Pharmacology of anti-cancer drugs 

Pharmacology of anti-cancer drugs
Chapter:
Pharmacology of anti-cancer drugs
Author(s):

Luis Daverede

DOI:
10.1093/med/9780199590209.003.0005
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date: 10 August 2020

Fluorouracil (5FU) is an anti-metabolite that was rationally synthesised in the 1960s. The reduction of the pyrimidine ring by dihydropyrimidine dehydrogenase, widely expressed in tissues through out the body, is the rate limiting step dehydrogenase (DPD). Five percent of patients are DPD deficient and experience disproportionate toxicity

Capecitabine, tegafur and S-1 are oral prodrugs which are metabolised to 5FU and other metabolites. The first 2 have at least equal efficacy but better toxicity profiles than bolus 5FU regimens

Oxaliplatin is a member of the platinum family, that although has no recognised single agent activity has synergy with fluoropyrimidines against colorectal cancer. Cumulative neurotoxicity is the dose limiting toxicity

Irinotecan is a topoisomerase I inhibitor with both single agent activity and synergy with fluoropyrimidines against colorectal cancer. Aggressive early use of loperamide is important to prevent profuse diarrhoea

Bevacizumab, cetuximab and panitunumab are monoclonal antibodies, the former targets the vascular endothelial growth factor (VEGF) and is only active in combination with chemotherapy, the latter 2 target epidermal growth factor receptor (EGFR) and have single agent activity and at least an additive effect with chemotherapy against colorectal cancer.

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