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This is a **combination regimen** consisting of three small molecule drugs: capecitabine, celecoxib, and methotrexate. It is used as an oral, metronomic chemotherapy protocol—typically involving continuous, low-dose administration of each component. The main indications are for cancers that are recurrent, metastatic, or refractory to platinum-based therapy, notably in head and neck squamous cell carcinoma (HNSCC). - **Capecitabine** is an oral prodrug of 5-fluorouracil that interferes with DNA synthesis in tumor cells by inhibiting thymidylate synthase. - **Celecoxib** is a selective cyclooxygenase-2 (COX-2) inhibitor with antineoplastic and antiangiogenic properties. - **Methotrexate** is a folate antagonist that inhibits dihydrofolate reductase, blocking DNA synthesis and cellular replication. Together, these agents are believed to exert synergistic anti-tumor and antiangiogenic effects, aiming to overcome resistance and minimize toxicity compared to conventional dosing schedules. Recent clinical studies have shown that this regimen can achieve disease control and is generally well tolerated, with manageable side effects such as mild fatigue, mucositis, and anemia. The schedule is considered especially suitable for settings where conventional chemotherapy is not feasible due to cost or toxicity[5].
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