Table 2: List of chemotherapeutic and biologic agents for patients with mCRC.

PharmacokineticsMetabolismComments

5-Fluorouracil (5-FU) [13] 16 minutes (range 8–20 minutes)
Excreted via lung (as CO2) and urine
Hepatic by dihydropyrimidine dehydrogenase (DPD) to active metabolites 5-fluoroxyuridine monophosphate (F-UMP) and 5-5-fluoro-2’-deoxyuridine-5’-O-monophosphate (F-dUMP)Limited data in patients with total bilirubin > 5, may be treated with weekly infusion without adjustment [4].

Oxaliplatin [14]Protein bound
0.43 to 16.8 hours (distribution) and 391 hours (terminal)
Urinary excretion
Nonenzymatic No apparent alteration in clearance or toxicity in patients with severe liver dysfunction [3, 15, 16].

Irinotecan [17]SN-38 protein bound
irinotecan 6–12 hours; SN-38 ~10–20 hours
Excreted via urine 11–20% and via biliary tract
Hydrolyzed in the liver to active metabolite SN-38 which is further metabolized by glucuronidation by UDP-glucuronosyltransferase 1-1 (also known as UGT1A1) In patients with varying degrees of liver dysfunction, severe side effects, poor tolerability, and overall worsening of PS were noted. [2, 18, 19]

TAS-102 [10, 20]; combination drug consisting of alpha,alpha,alpha-trifluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI)Readily absorbed
FTD 1.4 hours, TPI 1.7–2.1 hours
Limited urinary excretion FTD; TPI 29% excreted via urine
FTD undergoes hepatic metabolism, TPI minimal hepatic metabolismPhase-I studies in patients with hepatic impairment are ongoing.

Regorafenib [21] for the drug 28 hours (14 to 58 hours; some metabolites may take longer for excretion, 32 to 70 hours)Hepatic by CYP3A4 and UGT1A9Severe drug induced liver injury has been reported with the use of drug; its use in patients with liver dysfunction would generally be avoided and requires close monitoring of liver function tests.

Monoclonal antibodies [5] long: days to weeksNo liver metabolism/clearanceGenerally acceptable to use if there are no other contraindications.

Anti-VEGF antibodies (bevacizumab/aflibercept) and antiepidermal growth factor (EGFR) antibodies (panitumumab/cetuximab) [1].