Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity.
Clofarabine is a second generation of purine nucleoside analogues designed to combine the most favorable pharmacokinetic properties of fludarabine and cladribine. Clofarabine acts by inhibiting DNA polymerases and ribonucleotide reductase as well as by inducing apoptosis in cycling and non-cycling cells. Phase I/II clinical studies revealed its efficacy in hematological malignancies, and in 2004 clofarabine was approved by the United States Food and Drug Administration for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia after at least two prior chemotherapy regimens. The mechanism of action, pharmacology and clinical activity of clofarabine is the subject of this review.
Lech-Maranda
Ewa
E
Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Pabianicka 62 str, 93-513 Lodz, Poland.
Korycka
Anna
A
Robak
Tadeusz
T
D000227:Adenine Nucleotides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000077866:Clofarabine; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D009705:Nucleosides / Q000737:chemistry*
D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D009705:Nucleosides; D000077866:Clofarabine