Table 2.
List of chemotherapeutic and biologic agents for patients with mCRC.
| Pharmacokinetics | Metabolism | Comments | |
|---|---|---|---|
| 5-Fluorouracil (5-FU) [13] |
T
1/2 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 T 1/2 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 T 1/2 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 T 1/2 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 metabolism | Phase-I studies in patients with hepatic impairment are ongoing. |
|
| |||
| Regorafenib [21] | T 1/2 for the drug 28 hours (14 to 58 hours; some metabolites may take longer for excretion, 32 to 70 hours) | Hepatic by CYP3A4 and UGT1A9 | Severe 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] | T 1/2 long: days to weeks | No liver metabolism/clearance | Generally acceptable to use if there are no other contraindications. |
∗Anti-VEGF antibodies (bevacizumab/aflibercept) and antiepidermal growth factor (EGFR) antibodies (panitumumab/cetuximab) [1].