fludarabine + gemcitabine

Fludarabine + gemcitabine is an investigational intravenous chemotherapy combination comprising two nucleoside analog antimetabolites used for hematologic malignancies, especially relapsed or refractory acute myeloid leukemia (AML) and evaluated preclinically in chronic lymphocytic leukemia (CLL). Both agents are deoxyadenosine or deoxycytidine analogs that undergo intracellular phosphorylation to active triphosphates, incorporate into DNA, and inhibit ribonucleotide reductase, leading to depletion of deoxynucleotide pools, impaired DNA synthesis, and apoptosis. In vitro studies show synergistic cytotoxicity in leukemic cells when low-dose gemcitabine is combined with fludarabine, likely because each drug’s active metabolite both inhibits ribonucleotide reductase and enhances the other’s incorporation into DNA, resulting in greater DNA chain termination, S-phase arrest, and apoptosis. Clinically, phase I regimens have used fludarabine given as short daily infusions over 5 days with prolonged fixed–dose-rate gemcitabine infusions to maximize intracellular active metabolite exposure while defining tolerability, with dose-limiting toxicities including stomatitis/esophagitis, myelosuppression, and infectious complications.

Other names

fludarabine and gemcitabinegemcitabine and fludarabine