Colon Cancer Medication

Updated: Nov 15, 2023
  • Author: Tomislav Dragovich, MD, PhD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Medication Summary

The fluoropyrimidine 5-fluorouracil (5-FU) remains the backbone of chemotherapy regimens for colon cancer, both in the adjuvant and metastatic setting. In addition to 5-FU, oral fluoropyrimidines such as capecitabine (Xeloda) and, outside the United States, tegafur are used as monotherapy or in combination with oxaliplatin (Eloxatin). Some of the standard combination regimens employ prolonged continuous infusion of 5-FU (FOLFIRI, FOLFOX) [177] or capecitabine (CAPOX, XELOX, XELIRI). [178, 179] For unresectable or metastatic colon cancer, treatment increasingly includes biologic agents, typically as targeted therapy based on genetic analysis of the tumor.

See also Colon Cancer Treatment Protocols



Antineoplastic Agent, Antimetabolite (pyrimidine analog)

Class Summary

These agents inhibit cell growth and proliferation.


Fluoropyrimidine analog. Cell cycle-specific with activity in the S-phase as single agent and has for many years been combined with biochemical modulator leucovorin. It inhibits DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific. Classic antimetabolite anticancer drug with chemical structure similar to endogenous intermediates or building blocks of DNA or RNA synthesis. 5-FU inhibits tumor cell growth through at least 3 different mechanisms that ultimately disrupt DNA synthesis or cellular viability. These effects depend on intracellular conversion of 5-FU into 5-FdUMP, 5-FUTP, and 5-FdUTP. 5-FdUMP inhibits thymidylate synthase (key enzyme in DNA synthesis), which leads to accumulation of dUMP, which then gets misincorporated into the DNA in the form of 5-FdUTP resulting in inhibition of DNA synthesis and function with cytotoxic DNA strand breaks. 5-FUTP is incorporated into RNA and interferes with RNA processing.

Capecitabine (Xeloda)

Fluoropyrimidine carbamate prodrug from of 5-fluorouracil (5-FU). Capecitabine itself is inactive. Undergoes hydrolysis in liver and tissues to form the active moiety (fluorouracil), inhibiting thymidylate synthetase, which in turn blocks methylation of deoxyuridylic acid to thymidylic acid. This step interferes with DNA and to a lesser degree with RNA synthesis.


Antidote, Folic Acid Antagonist

Class Summary

These agents counteract the toxic effects of the chemotherapeutic drug.


Reduced form of folic acid that does not require enzymatic reduction reaction for activation. Allows for purine and pyrimidine synthesis, both of which are needed for normal erythropoiesis. Current standard therapy for colon cancer involves combination chemotherapy. Binds to and stabilizes ternary complex of FdUTP (intracellular active metabolite of fluoropyrimidines) and thymidylate synthetase (TS), augmenting cytotoxic effects of 5-fluorouracil. Used as an adjunct to fluorouracil.


Antineoplastic Agent, Miscellaneous

Class Summary

Irinotecan is a topoisomerase I inhibitor. Trifluridine is a thymidine-based nucleoside analog that is combined with the thymidine phosphorylase inhibitor, tipiracil.

Irinotecan (Camptosar)

Semisynthetic derivative of camptothecin, an alkaloid extract from the Camptotheca acuminate tree. Inactive in its parent form. Converted by the carboxylesterase enzyme to its active metabolite from, SN-38.

SN-38 binds to and stabilizes the topoisomerase I-DNA complex and prevents the relegation of DNA after it has been cleaved by topoisomerase I, inhibiting DNA replication. Current standard therapy for metastatic colon cancer involves combination of 5-FU/LV/CPT11 chemotherapy (see Standard Therapy).

Because of toxicity problems associated with Saltz regimen (5-FU/LV/CPT11), now standard first-line therapy for metastatic colon cancer, maximum of 400 mg/m2 of 5-FU and 100 mg/m2 of CPT11 can be used as starting dose.

Tipiracil/trifluridine (Lonsurf)

Trifluridine is a thymidine-based nucleoside analog that incorporates into DNA, interferes with DNA synthesis, and inhibits cell proliferation. Tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase. The combination product is indicated, as a single agent or in combination with bevacizumab, for metastatic colorectal cancer in patients previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.


Antineoplastic Agent, Alkylating Agent

Class Summary

Oxaliplatin is a platinum analog.


Third-generation platinum-based antineoplastic agent used in combination with an infusion of 5-fluorouracil (5-FU) and leucovorin for treatment of metastatic colorectal cancer in patients with recurrence or progression following initial treatment with irinotecan, 5-FU, and leucovorin. Also indicated for previously untreated advanced colorectal cancer in combination with 5-FU and leucovorin. Covalently binds to DNA with preferential binding to the N-7 position of guanine and adenine. DNA mismatch repair enzymes are unable to recognize oxaliplatin-DNA adducts in contrast with other platinum-DNA adducts as a result of their bulkier size. Forms interstrand and intrastrand Pt-DNA crosslinks that inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific with activity in all phases of the cell cycle.


Antineoplastic Agent, Monoclonal Antibody

Class Summary

These agents target factors responsible for deregulated cell proliferation.

Cetuximab (Erbitux)

Recombinant, human/mouse chimeric monoclonal antibody that specifically binds to the extracellular domain of human epidermal growth factor receptors (EGFR, HER1, c-ErbB-1). Cetuximab-bound EGF receptor inhibits activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased production of matrix metalloproteinase and vascular endothelial growth factor.

Indicated for treatment of KRAS mutation-negative (wild-type) EGFR-expressing, metastatic colorectal cancer for the following: 1) in combination with FOLFIRI for first-line treatment, 2) in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy, and 3) as a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan.

Bevacizumab (Avastin, Mvasi)

Murine derived monoclonal antibody that inhibits angiogenesis by targeting and inhibiting vascular endothelial growth factor (VEGF). Inhibiting new blood vessel formation denies blood, oxygen, and other nutrients needed for tumor growth. Bevacizumab is indicated in combination with a fluoropyrimidine-based chemotherapy as a first-line or second-line treatment for metastatic colorectal cancer. It is also indicated for second-line treatment in patients who have progressed on a first-line bevacizumab-containing regimen. For continuation therapy, use bevacizumab in combination with a fluoropyrimidine (eg, 5-FU, capecitabine) plus irinotecan or oxaliplatin-based chemotherapy. Mvasi has been FDA-approved as a biosimilar to Avastin but not as an interchangeable product.

Panitumumab (Vectibix)

Recombinant human IgG2 kappa monoclonal antibody that binds to human epidermal growth factor receptor (EGFR). Indicated for wild-type KRAS (exon 2 in codons 12 or 13) metastatic colororectal carcinoma, as determined by an FDA-approved test. Indicated as second-line, monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. Also indicated as first-line therapy in combination with FOLFOX.

Ipilimumab (Yervoy)

Recombinant human cytotoxic T-lymphocyte antigen 4 (CTLA-4) - blocking antibody. It is indicated in combination with nivolumab for adults with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) which progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.


Antineoplastics, Tyrosine Kinase Inhibitors

Class Summary

VEGF induces endothelial cell proliferation and blood vessel permeability. Inhibiting VEGF prevents tyrosine kinase stimulation. 

Ziv-aflibercept (Zaltrap)

Vascular endothelial growth factor (VEGF) inhibitor; prevents VEGF from stimulating cellular responses by binding to tyrosine kinase receptors (ie, the VEGF receptors). Indicated in combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) for metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin regimen.

Regorafenib (Stivarga)

Regorafenib is a tyrosine kinase inhibitor. It is indicated for metastatic colorectal cancer in patients who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF therapy (eg, bevacizumab, ziv-aflibercept); and, if KRAS wild type, an anti-EGFR therapy (eg, cetuximab, panitumumab).

Tucatinib (Tukysa)

Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro and in vivo, tucatinib inhibits the antitumor activity of HER2-expressing tumor cells and inhibits the growth of HER2-expressing tumors. The combination of tucatinib with trastuzumab showed an increase in antitumor activity  in vitro and in vivo. The FDA granted accelerated approval for tucatinib in combination with trastuzumab for adults with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed after treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy.


Antineoplastics, VEGF Inhibitor

Class Summary

Vascular endothelial growth factor (VEGF) receptor antagonists disrupt ligand-induced proliferation and migration of human endothelial cells. Angiogenesis requires the binding of signaling molecules (eg, VEGF) to receptors on the surface of normal endothelial cells. When VEGF and other endothelial growth factors bind to their receptors on endothelial cells, signals within these cells are initiated that promote the growth and survival of new blood vessels. When VEGF is bound, angiogenesis is inhibited.

Ramucirumab (Cyramza)

Ramucirumab specifically binds VEGF receptor 2 and blocks binding of VEGFR ligands, VEGF-A, VEGF-C, and VEGF-D. It is indicated for use in combination with FOLFIRI for the treatment of patients with metastatic colorectal cancer (mCRC) whose disease has progressed on a first-line bevacizumab-, oxaliplatin- and fluoropyrimidine-containing regimen.

Fruquintinib (Fruzaqla)

Fruquintinib is a selective and potent oral inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. It is indicated for metastatic colorectal cancer (mCRC) in adults who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.


PD-1/PD-L1 Inhibitors

Class Summary

Tumor cells may circumvent T-cell–mediated cytotoxicity by expressing PD-L1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells.

Pembrolizumab (Keytruda)

Monoclonal antibody to programmed cell death-1 protein (PD-1); blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation. It is indicated for unresectable or metastatic colon cancer that has tested positive for microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR), and has progressed following treatment with a fluoropyrimidine (eg, 5-FU, capecitabine), oxaliplatin, and irinotecan.

Nivolumab (Opdivo)

Nivolumab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits programmed cell death-1 (PD-1) activity by binding to the PD-1 receptor to block the ligands PD-L1 and PD-L2 from binding. The negative PD-1 receptor signaling that regulates T-cell activation and proliferation is therefore disrupted. This releases PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response. It is indicated for unresectable or metastatic colon cancer that has tested positive for microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR), and has progressed following treatment with a fluoropyrimidine (eg, 5-FU, capecitabine), oxaliplatin, and irinotecan in patients ≥ 12 years. Additionally, it is also indicated in combination with ipilimumab for adults.


Antineoplastics, Other

Class Summary

Larotrectinib selectively inhibits tropomyosin receptor kinases (TRKs). Entrectinib and its major metabolite TRKs, proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK). [180]  

Larotrectinib (Vitrakvi)

Highly selective inhibitor of tropomyosin receptor kinases (TRK), TRKA, TRKB, and TRKC. In tumor models, larotrectinib demonstrates antitumor activity in cells by activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK overexpression

Entrectinib (Rozlytrek)

Selectively inhibits TRKA, TRKB, and TRKC. Indicated for adults and children aged 12 years or older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation.


Antineoplastics, BRAF Kinase Inhibitor

Class Summary

This pathway regulates several key cellular activities, including proliferation, differentiation, survival, and angiogenesis; inappropriate activation of proteins in this pathway has been shown to occur in many cancers.

Encorafenib (Braftovi)

Encorafenib inhibits in vitro growth of tumor cell lines expressing BRAF V600 E, D, and K mutations. It is indicated in combination with cetuximab for metastatic colorectal cancer (CRC) in patients with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.