glufosfamide + gemcitabine

A combination of **glufosfamide** (a glycosidic conjugate of β-D-glucose and isophosphoramide mustard, an active alkylating moiety of ifosfamide) and **gemcitabine** (a deoxycytidine analog), both used for their cytotoxic effects against rapidly dividing cells. Glufosfamide targets tumor cells by exploiting the upregulated glucose uptake mechanism in certain cancers, where it is transported into the cell and hydrolyzed to release the DNA-alkylating isophosphoramide mustard. Gemcitabine is phosphorylated intracellularly and its active triphosphate metabolite incorporates into DNA, causing chain termination and apoptosis. This combination has been studied in advanced pancreatic adenocarcinoma, with evidence of synergistic activity due to enhanced DNA damage (from glufosfamide) and impaired DNA repair and synthesis (from gemcitabine). Principal toxicities include hematologic suppression and renal toxicity[1][2][3][5][6].