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| Treatment | Mechanism |
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| Drugs used in conventional chemotherapy treatments |
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| 5-fluorouracil (5FU) | Inhibition of nucleotide biosynthesis. Prodrug. Entering the cell through uracil transport system. Intracellular transformation into FdUMP, FdUTP, and FUTP. |
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Capecitabine
(Xeloda) | Metabolic precursor of 5FU. Requiring the activity of carboxylesterase, cytidine deaminase, and uridine phosphorylase. |
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Methotrexate
(MTX) | Blocking nucleotide biosynthesis as it is a potent competitive inhibitor of dihydrofolate reductase, an enzyme that participates in the tetrahydrofolate synthesis (required for de novo biosynthesis of purine and pyrimidine bases). |
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Leucovorin
(Wellcovorin) | Calcium folinate. Enhancing 5FU activity. It is a 5-formyl derivative of tetrahydrofolic acid and is readily converted to other reduced folic acid derivatives (e.g., tetrahydrofolate). It does not require dihydrofolate reductase activation and may activate this enzyme and is used in rescue therapies after methotrexate treatment. |
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Oxaliplatin
(Eloxatin) | Platinum containing compound that form inter- and intrastrand crosslinks in DNA, blocking replication and transcription.
Approved by the FDA in 2002. |
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Cisplatin
(Platinol, CDDP) | Platinum containing compound that form inter- and intrastrand crosslinks in DNA, blocking replication and transcription. |
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Irinotecan (CPT-11)
(Camptosar) | Camptothecin derived prodrug. Irinotecan is activated by hydrolysis to SN-38, an inhibitor of topoisomerase I and, thus, blocks replication and transcription. |
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Regorafenib
(Stivarga) | Multikinase inhibitor which targets angiogenic, stromal, and oncogenic receptor tyrosine kinase (RTKs).
Approved by the FDA in 2012. |
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| Combined chemotherapy regimens |
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| FOLFOX | Leucovorin (folinic acid) + 5FU + oxaliplatin (stages III & IV).
Approved by the FDA in 2002 for refractory tumors and in 2004 for first-line treatments of metastatic colorectal cancer. |
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| CapOX (XELOX) | Capecitabine + oxaliplatin (stages III & IV). |
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| FOLFIRI (IFL) | Leucovorin (folinic acid) + 5FU + irinotecan (stage IV). |
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| FOLFIRINOX | Leucovorin (Folinic acid) + 5FU + irinotecan + oxaliplatin (stage IV). |
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| FL | 5FU + leucovorin (folinic acid).
Approved by the FDA in 1991 for first-line treatment of metastatic colorectal cancer. |
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| Monoclonal antibodies for targeted therapy of metastatic CRC |
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Cetuximab
(Erbitux) | Cetuximab is a recombinant, human-mouse chimeric IgG1 monoclonal antibody that binds specifically to the extracellular domain of the human epidermal growth factor receptor (EGFR) on both normal and tumor cells and competitively inhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforming growth factor α.
Approved by the FDA in 2004 for use, in combination with irinotecan, for the treatment of EGFR-expressing, metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy. In 2012, approved for use in combination with FOLFIRI for first-line treatment of patients with wild-type K-ras. |
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Panitumumab
(Vectibix) | Human mAb against EGFR (similar to cetuximab).
Approved by the FDA in 2006 for the treatment of patients with EGFR-expressing, metastatic colorectal cancer with disease progression. on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. |
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Bevacizumab
(Avastin) | Bevacizumab is a recombinant humanized monoclonal antibody that binds to human vascular endothelial growth factor (VEGF), thereby preventing the interaction of VEGF with its receptors on the surface of endothelial cells.
Approved by the FDA in 2013 for use in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for the treatment of patients with metastatic colorectal cancer. |
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Ziv-aflibercept
(Zaltrap) | Recombinant fusion protein consisting of VEGF-binding portions from the extracellular domains of human VEGFR1 and 2, that are fused to the Fc portion of the human IgG1 immunoglobulin. It binds and inhibits VEGF-A, VEGF-B, and placental growth factor. It blocks angiogenesis and decreases vascular permeability.
Approved by the FDA in 2012 for use in combination with FOLFIRI for the treatment of patients with metastatic colorectal cancer that is resistant to or has progressed following treatment with an oxaliplatin-containing regimen. |
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Ramucirumab
(Cyramza) | Human mAb against VEGFR2. Inhibits angiogenesis by blocking the interaction between VEGF and VEGFR2.
Approved by the FDA in 2015 for use in combination with FOLFIRI for the treatment of patients with metastatic colorectal cancer whose disease has progressed on a first-line regimen containing bevacizumab, oxaliplatin, and a fluoropyrimidine. |
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