surufatinib + tegafur + gimeracil + oteracil + temozolomide

The combination of surufatinib, tegafur, gimeracil, oteracil, and temozolomide is an investigational oral combination regimen being evaluated for the treatment of advanced neuroendocrine tumors (NETs), particularly MGMT-low advanced pancreatic neuroendocrine tumors (pNETs). This regimen, also referred to as the SUSTEM regimen, combines the multi-targeted tyrosine kinase inhibitor surufatinib with the oral fluoropyrimidine S-1 (a fixed-dose combination of tegafur, gimeracil, and oteracil) and the alkylating agent temozolomide. Surufatinib selectively inhibits VEGFR-1, -2, and -3, FGFR-1, and CSF-1R, thereby blocking tumor angiogenesis and modulating tumor-associated macrophages to promote an immune response. S-1 delivers tegafur, a prodrug of 5-fluorouracil (5-FU) that inhibits thymidylate synthase, alongside gimeracil (a dihydropyrimidine dehydrogenase inhibitor that prevents 5-FU degradation) and oteracil (which reduces gastrointestinal toxicity). Temozolomide is a DNA alkylating agent that induces cell death, particularly in tumors with low levels of O6-methylguanine-DNA methyltransferase (MGMT). This combination is being studied in clinical trials to determine if the synergistic effects of anti-angiogenesis, macrophage modulation, and dual-agent chemotherapy can improve outcomes in patients with advanced neuroendocrine malignancies.

Other names

SUSTEM regimenSUSTEM-p regimensurufatinib + S-1 + TMZsurufatinib + S-1 + temozolomidesurufatinib + S-1/temozolomidesurufatinib + tegafur-gimeracil-oteracil + temozolomidesurufatinib + tegafur/gimeracil/oteracil + temozolomidesurufatinib + temozolomide + S-1