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SIR-Spheres + fluorouracil is a combination therapy consisting of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres (marketed as SIR-Spheres) and systemic chemotherapy with the antimetabolite drug fluorouracil (5-FU). The mechanism of action involves two modalities: 1. **SIR-Spheres** deliver targeted internal radiotherapy directly to liver tumors via hepatic arterial infusion, emitting beta radiation that induces localized tumor cell death while sparing surrounding healthy tissue. 2. **Fluorouracil** is a pyrimidine analog that inhibits thymidylate synthase, disrupting DNA synthesis and leading to cytotoxicity in rapidly dividing cancer cells. This combination has been studied primarily for the treatment of unresectable or metastatic colorectal cancer with liver-dominant disease, aiming to improve local tumor control and progression-free survival compared to chemotherapy alone[3][4][6]. Clinical trials have shown increased response rates and time to progression when adding SIR-Spheres to standard systemic chemotherapy regimens such as FOLFOX or leucovorin/fluorouracil[4][6]. However, this approach may be associated with higher rates of certain adverse events including hematologic toxicity and hepatic complications[4][5].
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