出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/06/25 12:07:27」(JST)[Wiki en表示]
|Systematic (IUPAC) name|
|Pregnancy cat.||D (US)|
|Legal status||℞-only (US)|
|Routes||Intravenous, subcutaneous, oral|
|Mol. mass||285.687 g/mol|
| Y (what is this?)
Cladribine (trade names Litak and Movectro) is a drug used to treat hairy cell leukemia (HCL, leukemic reticuloendotheliosis) and multiple sclerosis. Its chemical name is 2-chlorodeoxyadenosine (2CDA).
As a purine analog, it is a synthetic anti-cancer agent that also suppresses the immune system. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. It is easily destroyed by normal cells except for blood cells, with the result that it produces relatively few side effects and results in very little non-target cell loss.
Cladribine (as injections) is indicated [approved] for the treatment of symptomatic hairy cell leukemia.
It is under investigation for other B cell leukemias and lymphomas, such as mantle cell lymphoma, and for use in the treatment of multiple sclerosis.
According to the Histiocytosis Association of America, cladribine is used to treat histiocytosis.
In January 2010, a large clinical trial involving more than 1000 patients documented significant reduction in relapse rates in multiple sclerosis patients with use of oral cladribine and thus making its use as the first oral medication in multiple sclerosis patients, most likely in year .
Russia was the first country to approve it for treating multiple sclerosis on July 12, 2010. In the European Union, the European Medicines Agency's CHMP did not approve cladribine in the first application, as did the U.S. Food and Drug Administration (FDA). As of March 2, 2011, the FDA has rejected oral cladribine for multiple sclerosis, "acknowledging sufficient data on the drug’s efficacy in multiple sclerosis but requiring more data on safety and risk-benefit " 
June 2011 : Merck has decided to withdraw all marketing applications for cladribine tablets, and to stop selling it in Russia and Australia which had approved it.
Routes of administration
For hairy cell leukemia, cladribine can be given by i.v. infusion or subcutaneous (s.c.) injection.
For outpatient i.v. infusions, the delivery time (not including time to place the i.v. line) may range from one to four hours; two hours is most common. Continuous i.v. infusion may be chosen; this approach drips in the cladribine slowly, 24 hours a day using a portable pump and a central venous catheter or a PICC line. By contrast, s.c. injections take less than ten seconds per day.
The same total doses are given by both routes. Intravenous and s.c. routes have the same overall outcomes, and the s.c. route may be reduce the infections and other risks associated with venipuncture.
An oral tablet form of cladribine has been successfully tested in patients with relapsing multiple sclerosis.
Using either i.v. or s.c. routes of administration, cladribine can be administered on a daily or a weekly schedule. Daily schedules involve one s.c. injection or one i.v. infusion per day for five to seven consecutive days. Weekly schedules involve one injection or infusion each week, for five or six weeks. One cycle is normally sufficient to produce a complete response, but in the event of a partial response, cycles may safely be repeated one to three months after the end of the first cycle.
Actual doses are calculated according to the surface area of the patient's skin instead of by weight, and divided by the number of planned treatments.
All schedules produce the same benefits and disadvantages. Five-day and seven-day daily schedules give the same total amount of drug and have the same outcomes, including remissions and adverse effects. Daily and weekly schedules give the same total amount of drug and have the same outcomes, including similar proportions of complete responses and similar proportions of patients hospitalized for fevers and opportunistic infections.
Existing studies estimate that from 18% to 42% of patients will experience a fever after cladribine infusion. This is usually a transient fever which can be treated with acetaminophen (paracetamol). These fevers, which resolve in less than 48 hours, have no evidence of being related to infection.
However, some patients have fevers that last longer and may be caused by an infection. Very few infections have actually been documented, but they do happen, and these infections are largely responsible for the 3% mortality rate associated with cladribine therapy in HCL. Factors that increased the likelihood of a neutropenic fever (with or without concomitant infection) include: anemia, hypocholesterolemia, a high proportion of hairy cells in the bone marrow with a low proportion of myelopoietic cells, low albumin, and high C-reactive protein. These are all signs of an advanced case of HCL.
In patients with hairy cell leukemia, there is no benefit to using hormones such as filgrastim or Granulocyte macrophage colony-stimulating factor to raise white blood cell counts prophylactically. The use of these expensive drugs does not reduce the number of patients who experience fevers, the number of days that the fevers last, or the number of patients admitted to the hospital for antibiotic treatments. Therefore routine adjunctive use (that is, use when there are no signs of infection) is not recommended.
In addition to fevers, cladribine increases the risk of herpes virus infections, particularly shingles.
Some patients develop a rash after treatment. Nearly all patients who develop a rash are taking other drugs, notably allopurinol or a sulfa drug, which are known to cause rashes, and the rash is likely due to these drugs rather than to cladribine itself.
Some HCL patients will require blood transfusions of platelets or packed red blood cells.
Patients are expected to experience a decline in blood cell counts during treatment. Several weeks after successful treatment, cell counts will begin to rebound, with platelet and neutrophil counts recovering before red blood cells and T cells. T4 cell counts may never reach pre-disease levels. Patients are usually advised to avoid sick people and large crowds of people as well as to wash their hands and keep their hands away from their eyes, nose, and mouth until their neutrophil counts have recovered.
Many patients experience fatigue, even in the absence of anemia, but since fatigue is a common feature of the disease, this may be caused by the disease instead of by the drug.
This drug does not cause hair loss, vomiting, or other side effects that are commonly associated with "old style" alkylating chemotherapy drugs. However, peripheral neuropathy has been reported occasionally after repeated doses of cladribine in the treatment of hairy cell leukemia. Overdose may cause kidney damage.
According to the drug's FDA-approved prescribing information, the median time to normalization of blood counts in patients with hairy cell leukemia is: two weeks for platelets, five weeks for absolute neutrophil counts, eight weeks for hemoglobin, and nine weeks for a patient to have all three parameters normalized. Weeks are counted from the first day of treatment, and all patients were on a seven-day daily treatment schedule for these studies.
Cladribine was designed by Dennis A. Carson as an anti-lymphocyte compound. It was first synthesized at Brigham Young University.
In 2008, Ernest Beutler won the Wallace H. Coulter Award for Lifetime Achievement in Hematology from the Coulter Foundation and the American Society of Hematology in part because of the clinical trials he ran, which established cladribine as the most effective treatment for hairy cell leukemia (HCL).
- Else M, Dearden CE, Matutes E, et al. (March 2009). "Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis". Br. J. Haematol. 145 (6): 733–40. DOI:10.1111/j.1365-2141.2009.07668.x. PMID 19344416.
- Mantle Cell Lymphoma initiative
- Histiocytosis Association of America
- Giovannoni G, et al., NEJM 2010
- Hirschler, Ben (July 12, 2010). "UPDATE 1-Russia okays Merck KGaA's multiple sclerosis pill". Reuters. http://www.reuters.com/article/idCNLDE66B0GB20100712?rpc=44.
- "Oral Multiple Sclerosis Therapies Spark Excitement, Concern" Internal Medicine News, April, 2011. 
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- Multiple Sclerosis: The Big Questions- The MS Forum Workshop.
- Goodin D.SourceDouglas S Goodin MS Center at the University of California San Francisco 350 Parnassus Avenue Suite #908 San Francisco CA 94117 USA Tel: (415) 514-2464 Fax: (415) 514-2470 E-mail: firstname.lastname@example.org.
- International MS journal / MS Forum.Int MS J.2011 Sep;17(3):100-7.
- The American Academy of Neurology (AAN) Annual Meeting was held in Toronto, Canada from 10-17 April, 2010. As usual, multiple sclerosis (MS) featured prominently with about 450 poster and platform presentations on various aspects. Highlights were presentations on the controversial theory of venous o
- PMID 21689494
- Seventy-nine-year-old man with Langerhans cell histiocytosis treated with cladribine.
- Black A, Bershow A, Allen PS, Crowson AN.SourceCollege of Medicine, University of Oklahoma, Oklahoma City, Oklahoma.
- Journal of the American Academy of Dermatology.J Am Acad Dermatol.2011 Sep;65(3):681-3.
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- Cladribine Enhances Apoptotic Cell Death in Lung Carcinoma Cells Over-Expressing DNase γ
- Hayakawa Akemi,Suzuki Haruhiko,Kamei Yuzuru,Tanuma Sei-ichi,Magae Junji
- Biological & Pharmaceutical Bulletin 34(7), 1001-1004, 2011
- … We compared the cytotoxic effects of chemotherapeutic agents including cisplatin, 5-fluorouracil, vinorelbine and cladribine, on a human lung cancer cell line, A549, and its derivative transfected with the DNase γ gene. … We observed selective cytotoxicity of cladribine on the DNase γ-expressing sub-cell line of A549. … Cladribine induces selective apoptosis in DNase γ-expressing A549 cells, which depends on activation of caspases. …
- NAID 130000738087
- 多発性硬化症の治療--再発抑制薬の現状と新薬治療の展望 (AYUMI 多発性硬化症と視神経脊髄炎)
- 斎田 孝彦
- 医学のあゆみ 237(4), 303-306, 2011-04-23
- NAID 40018813865
- Cladribine (trade names Litak and Movectro) is a drug used to treat hairy cell leukemia (HCL, leukemic reticuloendotheliosis) and multiple sclerosis. Its chemical name is 2-chlorodeoxyadenosine (2CDA). As a purine analog, it is a synthetic ...