5-fluorouracil + amifostine + folinic acid

This is a combination regimen consisting of three agents: - **5-fluorouracil (5-FU):** A pyrimidine analog and antimetabolite chemotherapy drug that inhibits thymidylate synthase, leading to impaired DNA synthesis and cell death, particularly in rapidly dividing cancer cells. - **Folinic acid (leucovorin/calcium folinate):** Not a chemotherapy agent itself, but enhances the cytotoxic effect of 5-FU by stabilizing the binding of 5-FU’s active metabolite to thymidylate synthase, thereby increasing inhibition of DNA synthesis. Folinic acid also serves as a "rescue" agent in other regimens involving antifolates. - **Amifostine:** A cytoprotective adjuvant that acts as a prodrug converted in tissues to an active thiol metabolite. This metabolite scavenges free radicals and provides selective protection for normal tissues against the toxic effects of chemotherapy and radiation. This combination has been studied primarily for metastatic colorectal carcinoma. The addition of amifostine aims to reduce gastrointestinal toxicity (notably mucositis) associated with high-dose 5-FU/folinic acid regimens without compromising anti-tumor efficacy[1]. The regimen is administered intravenously.