Role of fludarabine in hematological malignancies.

Abstract

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.

• Authors: Marco Montillo, Francesca Ricci, Alessandra Tedeschi
• Journal: Expert review of anticancer therapy (Expert Rev Anticancer Ther) Vol. 6 Issue 9 Pg. 1141-61 (Sep 2006) ISSN: 1744-8328 [Electronic] England
• PMID: 17020450 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Prodrugs
• Vidarabine
• fludarabine

Topics

• Animals
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Hematologic Neoplasms (blood, drug therapy)
• Humans
• Prodrugs (pharmacokinetics, therapeutic use)
• Vidarabine (analogs & derivatives, pharmacokinetics, therapeutic use)