Table 1.

Mechanisms of action, metabolism, and excretion of drugs used in patients with gastrointestinal cancers.

Drugs	Indication	Mechanism of action	Metabolism	Renal excretion	Biliary excretion	Dose reduction
5-Fluorouracil	Colorectal cancer, gastric cancer	Antimetabolite, thymidylate synthase blocking	Thymidylate synthase, thymidylate phosphorylase, dihydropyrimidine dehydrogenase	Inactive metabolites in urine	Inactive metabolites in bile	Enzymatic catabolism by DPD in the liver (>90%); Biluribin > 5 mg/dL: omit use
Oxaliplatin	Colorectal cancer	Alkylator of DNA	–	50%	–	Reduce dose for renal dysfunction
Cisplatin	Anal cancer	Alkylator of DNA	–	90%	<10%	Creatinine clearance 10–50 mL/min: 25% reduction
Irinotecan	Colorectal cancer, gastric cancer	Topoisomerase I inhibition	Carboxylesterase, CYP3A4, UGT1A1, topoisomerase I	>25%	>50% hepatic metabolism and biliary excretion	Metabolized in the liver. Consider in the presence of hepatic dysfunction
Gemcitabine	Pancreatic carcinoma	Metabolized intracellularly to the active diphosphate and triphosphate	Cytidine deaminase, deoxycytidylate deaminase	Nearly entirely excreted in urine	–	Metabolized in the liver. Consider in the presence of hepatic dysfunction
Bevacizumab	Colorectal cancer	Monoclonal antibody for VEGF-A		–	–	–
Cetuximab	Colorectal cancer	Monoclonal antibody to EGFR		–	–	No adjustment needed for renal or hepatic impairment
Panitumumab	Colorectal cancer	Monoclonal antibody to EGFR
Erlotinib	Pancreas cancer	Inhibits intracellular phosphorylation of EGFR tyrosine kinase		8% renal elimination	Hepatic metabolism through CYP 3A4; 83% hepatic elimination	Consider in severe liver impairment

Abbreviations: VEGF = vascular endothelial growth factor; EGFR = epidermal growth factor receptor