Treating refractory leukemias in childhood, role of clofarabine.

Article Details

Citation

Harned TM, Gaynon PS

Treating refractory leukemias in childhood, role of clofarabine.

Ther Clin Risk Manag. 2008 Apr;4(2):327-36.

PubMed ID
18728851 [ View in PubMed
]
Abstract

Approximately 4000 children and adolescents under the age of 20 years develop acute leukemia per year in the US. Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Despite impressive improvements in outcome, relapsed ALL is the fourth most common pediatric malignancy. Therapy for relapsed ALL remains unsatisfactory, and the majority of relapse patients still succumb to leukemia. Between one-third and one-half of patients with acute myelogenous leukemia (AML) relapse, and no standard therapy is recognized for patients with relapsed and/or refractory AML. Novel therapeutic agents are needed to improve the cure rate for relapsed ALL and AML. Clofarabine is a next-generation nucleoside analog, designed to incorporate the best features and improve the therapeutic index of cladribine and fludarabine. Clofarabine inhibits both DNA polymerase and ribonucleotide reductase, leading to impaired DNA synthesis and repair, and directly induces apoptosis. Phase I and II single-agent trials in children have shown that clofarabine is safe and active in both myeloid and lymphoid relapsed/refractory acute leukemias. Clofarabine has been approved by the FDA for pediatric patients with relapsed/refractory ALL after at least 2 prior therapeutic attempts. Rational combinations of clofarabine with other active agents in refractory leukemias are currently under investigation.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
ClofarabineDNANucleotideHumans
Yes
Other/unknown
Details
ClofarabineDNA polymerase alpha catalytic subunitProteinHumans
Yes
Inhibitor
Details
ClofarabineRibonucleoside-diphosphate reductase large subunitProteinHumans
Yes
Inhibitor
Details