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Information |
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Drug Groups
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approved; investigational |
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Description
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Clofarabine is a purine nucleoside antimetabolite that is being studied in the treatment of cancer. It is marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra.
Clofarabine is used in paediatrics to treat a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia (ALL), only after at least two other types of treatment have failed. It is not known if the drug extends life expectancy. Some investigations of effectiveness in cases of acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out. |
| Indication |
For the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphocytic (lymphoblastic) leukemia after at least two prior regimens. It is designated as an orphan drug by the FDA for this use. |
| Pharmacology |
Clofarabine is a purine nucleoside antimetabolite that differs from other puring nucleoside analogs by the presence of a chlorine in the purine ring and a flourine in the ribose moiety. Clofarabine seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by clofarabine, other effects also occur. Clofarabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer cells. |
| Toxicity |
There were no known overdoses of clofarabine. The highest daily dose administered to a human to date (on a mg/m2 basis) has been 70 mg/m2/day × 5 days (2 pediatric ALL patients). The toxicities included in these 2 patients included grade 4 hyperbilirubinemia, grade 2 and 3 vomiting, and grade 3 maculopapular rash. |
| Affected Organisms |
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Humans and other mammals |
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| Biotransformation |
Clofarabine is sequentially metabolized intracellularly to the 5’-monophosphate metabolite by deoxycytidine kinase and mono- and di-phosphokinases to the active 5’-triphosphate metabolite. Clofarabine has high affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine. |
| Half Life |
The terminal half-life is estimated to be 5.2 hours. |
| Protein Binding |
47% bound to plasma proteins, predominantly to albumin. |
| Elimination |
Based on 24-hour urine collections in the pediatric studies, 49 - 60% of the dose is excreted in the urine unchanged. |
| Distribution |
* 172 L/m2 |
| Clearance |
* 28.8 L/h/m2 [Pediatric patients (2 - 19 years old) with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) receiving 52 mg/m2 dose] |
| References |
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Pession A, Masetti R, Kleinschmidt K, Martoni A: Use of clofarabine for acute childhood leukemia. Biologics. 2010 Jun 24;4:111-8.
[Pubmed]
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Harned TM, Gaynon PS: Treating refractory leukemias in childhood, role of clofarabine. Ther Clin Risk Manag. 2008 Apr;4(2):327-36.
[Pubmed]
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Lech-Maranda E, Korycka A, Robak T: Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Mini Rev Med Chem. 2009 Jun;9(7):805-12.
[Pubmed]
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Larson ML, Venugopal P: Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009 Jun;10(8):1353-7.
[Pubmed]
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Zhenchuk A, Lotfi K, Juliusson G, Albertioni F: Mechanisms of anti-cancer action and pharmacology of clofarabine. Biochem Pharmacol. 2009 Dec 1;78(11):1351-9. Epub 2009 Jul 1.
[Pubmed]
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| External Links |
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