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FOLFSIM is an investigational combination chemotherapy regimen consisting of Simmtecan, 5-fluorouracil (5-FU), and L-leucovorin (l-LV). Simmtecan is a novel derivative of irinotecan developed by the Shanghai Institute of Materia Medica, acting as a topoisomerase I inhibitor to prevent DNA religation and cause double-strand breaks. 5-fluorouracil is an antimetabolite that inhibits thymidylate synthase, thereby disrupting DNA synthesis, while L-leucovorin is a folate analog that enhances the binding of 5-FU to thymidylate synthase, increasing its cytotoxic effect. This regimen is primarily being investigated by Peking University for the treatment of advanced or metastatic neuroendocrine carcinoma, often in combination with the PD-1 checkpoint inhibitor toripalimab.
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