Role of fludarabine in hematological malignancies.
Fludarabine is a prodrug that is converted to the free nucleoside 9-beta-D-arabinosyl-2-fluoroadenine (F-ara-A), which enters cells and accumulates mainly as the 5'-triphosphate, F-ara-ATP. F-ara-ATP has multiple mechanisms of action, which are mostly directed toward DNA. Collectively, these actions affect DNA synthesis, which is the major mechanism of F-ara-A-induced cytotoxicity. Secondarily, incorporation into RNA and inhibition of transcription has been shown in cell lines. As a single agent, fludarabine has been effective for indolent leukemia. Biochemical modulation strategies resulted in enhanced accumulation of cytarabine triphosphate and led to the use of fludarabine for the treatment of acute leukemia. The combination of fludarabine with DNA-damaging agents to inhibit DNA repair processes has been highly effective for indolent leukemia and lymphomas. Other strategies have incorporated fludarabine into preparative regimens for nonmyeloablative stem-cell transplantation.
Montillo
Marco
M
Department of Oncology/Haematology, Division of Haematology, Niguarda Ca'[Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy. marco.montillo@ospedaleniguarda.it
Ricci
Francesca
F
Tedeschi
Alessandra
A
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D011355:Prodrugs / Q000493:pharmacokinetics / Q000627:therapeutic use; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000970:Antineoplastic Agents; D011355:Prodrugs; D014740:Vidarabine; C024352:fludarabine