5-fluorouracil + interferon alpha-2a

This is a combination therapy consisting of 5-fluorouracil (5-FU), an antimetabolite chemotherapeutic agent, and interferon alpha-2a (IFN-alpha-2a), a recombinant cytokine. The combination has been investigated primarily for the treatment of metastatic gastrointestinal cancers such as gastric carcinoma and colorectal cancer. **Mechanism of Action:** 5-fluorouracil acts mainly by inhibiting thymidylate synthase, leading to impaired DNA synthesis and cell death in rapidly dividing tumor cells[9]. Interferon alpha-2a binds to type I interferon receptors (IFNAR1/IFNAR2c) on target cells, activating the JAK/STAT pathway and upregulating immunomodulatory proteins[8]. When used together, IFN-alpha can enhance the cytotoxic effects of 5-FU by increasing intracellular levels of active metabolites like FdUMP and modulating enzymes involved in nucleotide metabolism[6][5]. The combination also induces cell cycle arrest, apoptosis via regulation of apoptosis-related proteins (e.g., Bcl-2 family), antiangiogenic effects through downregulation of VEGF pathways, and immunomodulation including increased MHC class I expression[6][8][9]. **Clinical Data:** Phase II trials have shown modest activity with significant toxicity in metastatic gastric carcinoma; response rates ranged from approximately 25% to over 40% depending on regimen intensity. Toxicities include granulocytopenia/neutropenia, mucositis, diarrhea, fatigue, skin rash; dose-limiting toxicities are common at higher doses[1][3].

Other names

5-FU + IFN-alpha-2afluorouracil + interferon alfa-2a5-fluorouracil and recombinant alpha-2a-interferon