cetuximab + leucovorin + fluorouracil + irinotecan

Cetuximab + leucovorin + fluorouracil + irinotecan is a combination chemoimmunotherapy regimen consisting of the anti-EGFR monoclonal antibody cetuximab (Erbitux) and the FOLFIRI chemotherapy regimen (irinotecan, fluorouracil, and leucovorin). This combination is primarily indicated as a first-line treatment for patients with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type metastatic colorectal cancer (mCRC). Cetuximab binds to the extracellular domain of EGFR, inhibiting ligand binding and downstream MAPK and PI3K/Akt signaling pathways to suppress tumor cell growth and survival. Irinotecan is a small-molecule prodrug that is metabolized to SN-38, a potent inhibitor of DNA topoisomerase I, which prevents DNA replication and induces double-strand DNA breaks. Fluorouracil (5-FU) is an antimetabolite that is converted intracellularly to fluorodeoxyuridine monophosphate (FdUMP), which inhibits thymidylate synthase to disrupt pyrimidine synthesis. Leucovorin (folinic acid) acts as a biochemical modulator that stabilizes the covalent ternary complex between FdUMP and thymidylate synthase, thereby enhancing the cytotoxic efficacy of fluorouracil. The efficacy of this combination was demonstrated in the landmark Phase III CRYSTAL trial, which showed significant improvements in overall survival, progression-free survival, and objective response rates in patients with RAS wild-type tumors.

Other names

Erbitux + FOLFIRIFOLFIRI + cetuximabFOLFIRI-cetuximabcetuximab + FOLFIRIcetuximab + leucovorin + fluorouracil + irinotecancetuximab, leucovorin, fluorouracil, and irinotecanmFOLFIRI + cetuximabmodified FOLFIRI + cetuximab