TY - JOUR
T1 - Clofarabine
T2 - Past, present, and future
AU - Kantarjian, Hagop M.
AU - Jeha, Sima
AU - Gandhi, Varsha
AU - Wess, Michael
AU - Faderl, Stefan
N1 - Funding Information:
This work was supported in part by grant CA57629 from the National Cancer Institute, Department of Health and Human Services.
PY - 2007/10
Y1 - 2007/10
N2 - Clofarabine is a second generation purine nucleoside analogue designed to overcome the limitations and to incorporate the best qualities of both cladribine and fludarabine. Clofarabine is thought to work via three mechanisms: inhibition of ribonucleotide reductase; incorporation into DNA; and induction of apoptosis. Given these mechanisms of action, clofarabine would be predicted to act synergistically with other chemotherapeutic agents such as other purine nucleoside analogues and DNA damaging or cross linking agents such as anthracyclines and platinum-based compounds. Intravenous clofarabine showed significant efficacy in pediatric leukemias (specifically, acute lymphoblastic leukemia (ALL)) and, in 2004, it was approved by the United States Food and Drug Administration (FDA) for the treatment of pediatric relapsed/ refractory ALL after at least two prior regimens. In adults, clofarabine has shown significant efficacy in hematologic malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) alone and in combinations. Ongoing and future studies will examine the use of clofarabine in elderly patients with AML for whom standard regimens are too toxic, and in MDS with intravenous and oral forms of the drug.
AB - Clofarabine is a second generation purine nucleoside analogue designed to overcome the limitations and to incorporate the best qualities of both cladribine and fludarabine. Clofarabine is thought to work via three mechanisms: inhibition of ribonucleotide reductase; incorporation into DNA; and induction of apoptosis. Given these mechanisms of action, clofarabine would be predicted to act synergistically with other chemotherapeutic agents such as other purine nucleoside analogues and DNA damaging or cross linking agents such as anthracyclines and platinum-based compounds. Intravenous clofarabine showed significant efficacy in pediatric leukemias (specifically, acute lymphoblastic leukemia (ALL)) and, in 2004, it was approved by the United States Food and Drug Administration (FDA) for the treatment of pediatric relapsed/ refractory ALL after at least two prior regimens. In adults, clofarabine has shown significant efficacy in hematologic malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) alone and in combinations. Ongoing and future studies will examine the use of clofarabine in elderly patients with AML for whom standard regimens are too toxic, and in MDS with intravenous and oral forms of the drug.
KW - Acute lymphoblastic leukemia
KW - Clofarabine
KW - Purine nucleoside analogue
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U2 - 10.1080/10428190701545644
DO - 10.1080/10428190701545644
M3 - Review article
C2 - 17852710
AN - SCOPUS:35148887258
SN - 1042-8194
VL - 48
SP - 1922
EP - 1930
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 10
ER -