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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/05 11:17:30」(JST)

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Fludarabine or fludarabine phosphate (Fludara) is a chemotherapy drug used in the treatment of hematological malignancies (cancers of blood cells such as leukemias and lymphomas). It is a purine analog, which interferes with DNA synthesis.

Indications[edit]

Fludarabine is highly effective in the treatment of chronic lymphocytic leukemia, producing higher response rates than alkylating agents such as chlorambucil alone.^[1] Fludarabine is used in various combinations with cyclophosphamide, mitoxantrone, dexamethasone and rituximab in the treatment of indolent non-Hodgkins lymphomas. As part of the FLAG regimen, fludarabine is used together with cytarabine and granulocyte colony-stimulating factor in the treatment of acute myeloid leukaemia. Because of its immunosuppressive effects, fludarabine is also used in some conditioning regimens prior to allogeneic stem cell transplant.

Pharmacology[edit]

Fludarabine is a purine analog, and can be given both orally and intravenously. Fludarabine inhibits DNA synthesis by interfering with ribonucleotide reductase and DNA polymerase. It is active against both dividing and resting cells. Being phosphorylated, fludarabine is ionized at physiologic pH and is effectually trapped in blood. This provides some level of specificity for blood cells, both cancerous and healthy.

Side effects[edit]

Fludarabine is associated with profound lymphopenia, and as a consequence, increases the risk of opportunistic infections significantly. Patients who have been treated with fludarabine will usually be asked to take co-trimoxazole or to use monthly nebulised pentamidine to prevent Pneumocystis jiroveci pneumonia. The profound lymphopenia caused by fludarabine renders patients susceptible to transfusion-associated graft versus host disease, a fatal complication of blood transfusion. For this reason, all patients who have ever received fludarabine should only be given irradiated blood components.

Fludarabine causes anemia, thrombocytopenia and neutropenia, requiring regular blood count monitoring. Some patients require blood and platelet transfusion, or G-CSF injections to boost neutrophil counts.

Fludarabine is associated with the development of severe autoimmune hemolytic anemia in a proportion of patients.^[2]

Difficulties are often encountered when harvesting peripheral blood stem cells from patients previously treated with fludarabine.^[3]

History[edit]

Fludarabine was produced by John Montgomery and Kathleen Hewson of the Southern Research Institute in 1968.^[4] Their previous work involved 2-fluoroadenosine, which was unsafe for use in humans; the change to this arabinose analogue was inspired by the success of vidarabine.^[4]

References[edit]

^ Rai KR et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000;343:1750-7. doi:10.1056/NEJM200012143432402 PMID 11114313
^ Gonzalez H et al. Severe autoimmune hemolytic anemia in eight patients treated with fludarabine. Hematol Cell Ther. 1998;40:113-8. PMID 9698219
^ Tournilhac O et al. Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood 2004;103:363-5. PMID 12969985
^ ^a ^b Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 258. ISBN 0-471-89979-8.

External links[edit]

Fludara webpage

UpToDate Contents

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1. 症候性または進行した慢性リンパ性白血病に対する初期治療の選択 selection of initial therapy for symptomatic or advanced chronic lymphocytic leukemia
2. リンパ腫の治療プロトコル treatment protocols for lymphoma
3. 血液悪性腫瘍を有する成人における侵襲性真菌感染症予防 prophylaxis of invasive fungal infections in adults with hematologic malignancies
4. 進行期（III/IV）濾胞性リンパ腫の初期治療 initial treatment of advanced stage iii iv follicular lymphoma
5. 再発性または難治性のマントル細胞リンパ腫の治療 treatment of relapsed or refractory mantle cell lymphoma

English Journal

Conditioning with treosulfan and fludarabine for patients with refractory or relapsed non-Hodgkin lymphoma.

Schmitt M1, Trenschel R2, Sayer HG3, Schneider C4, Glass A5, Hilgendorf I4, Treschl A3, Junghanss C4, Borchert K4, Koenigsmann M6, Casper J7, Beelen DW2, Freund M4, Kahl C8.
Molecular and clinical oncology.Mol Clin Oncol.2014 Sep;2(5):773-782. Epub 2014 Jun 2.
The treatment of refractory or relapsed non-Hodgkin lymphoma (NHL) remains challenging. In this retrospective study, 88 patients with refractory or relapsed NHL received treosulfan and fludarabine as a reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT).
PMID 25054045

Phase I study of the safety and pharmacokinetics of plerixafor in children undergoing a second allogeneic hematopoietic stem cell transplantation for relapsed or refractory leukemia.

Srinivasan A1, Panetta JC2, Cross SJ2, Pillai A3, Triplett BM3, Shook DR3, Dallas MH3, Hartford C4, Sunkara A5, Kang G5, Jacobsen J6, Choi J7, Leung W3.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.Biol Blood Marrow Transplant.2014 Aug;20(8):1224-8. doi: 10.1016/j.bbmt.2014.04.020. Epub 2014 Apr 23.
The safety, pharmacokinetics, and biological effect of plerixafor in children as part of a conditioning regimen for chemo-sensitization in allogeneic hematopoietic stem cell transplantation (HSCT) have not been studied. This is a phase I study of plerixafor designed to evaluate its tolerability at d
PMID 24769325

Increasing chimerism after allogeneic stem cell transplantation is associated with longer survival time.

Tang X1, Alatrash G2, Ning J3, Jakher H4, Stafford P4, Zope M4, Shpall EJ4, Jones RB4, Champlin RE4, Thall PF3, Andersson BS4.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.Biol Blood Marrow Transplant.2014 Aug;20(8):1139-44. doi: 10.1016/j.bbmt.2014.04.003. Epub 2014 Apr 13.
Donor chimerism after allogeneic stem cell transplantation (allo-SCT) is commonly used to predict overall survival (OS) and disease-free survival (DFS). Because chimerism is observed at 1 or more times after allo-SCT and not at baseline, if chimerism is in fact associated with OS or DFS, then the oc
PMID 24727332

Japanese Journal

臨床研究高齢者骨髄性造血器腫瘍に対するフルダラビン/メルファラン/全身放射線照射を前処置とした同種造血幹細胞移植

中邑伸幸,森毅彦,加藤淳 [他]
臨床血液 53(3), 318-322, 2012-03
NAID 40019251114

慢性リンパ性白血病に対するfludarabine+cyclophosphamide±rituximabの第？相試験 (特集血液腫瘍に対する重要な臨床試験の意義と診療・研究へのインパクト)

高松泰,鈴宮淳司
血液内科 64(1), 43-52, 2012-01
NAID 40019197332

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★リンクテーブル★

リンク元	「フルダラビン」
拡張検索	「fludarabine phosphate」

「フルダラビン」

Fludarabine
Systematic (IUPAC) name
	[(2R,3R,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl]methoxyphosphonic acid
Clinical data
Trade names	Fludara
AHFS/Drugs.com	monograph
MedlinePlus	a692003
Pregnancy cat.	D
Legal status	Prescription Only (S4) (AU) POM (UK)
Routes	Intravenous, oral
Pharmacokinetic data
Bioavailability	55%
Protein binding	19 to 29%
Half-life	20 hours
Excretion	Renal
Identifiers
CAS number	75607-67-9
ATC code	L01BB05
PubChem	CID 657237
DrugBank	DB01073
ChemSpider	571392
UNII	P2K93U8740
KEGG	D01907
ChEBI	CHEBI:63599
ChEMBL	CHEMBL1568
Chemical data
Formula	C10H13FN5O7P
Mol. mass	365.212 g/mol
	SMILES Fc1nc(c2ncn(c2n1)[C@@H]3O[C@@H]([C@@H](O)[C@@H]3O)CO)N;
	InChI InChI=1S/C10H12FN5O4/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(19)5(18)3(1-17)20-9/h2-3,5-6,9,17-19H,1H2,(H2,12,14,15)/t3-,5-,6+,9-/m1/s1 ; Key:HBUBKKRHXORPQB-FJFJXFQQSA-N ;
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　　[★]

英: fludarabine
化: リン酸フルダラビン, fludarabine phosphate
商: フルダラ, Fludara
関: 抗悪性腫瘍薬

抗悪性腫瘍薬
低悪性度B細胞性非ホジキンリンパ腫、マントル細胞リンパ腫など

「fludarabine phosphate」

　　[★] フルダラビン、リン酸フルダラビン

[Rai-1] Rai KR et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000;343:1750-7. doi:10.1056/NEJM200012143432402 PMID 11114313

[Gonzalez-2] Gonzalez H et al. Severe autoimmune hemolytic anemia in eight patients treated with fludarabine. Hematol Cell Ther. 1998;40:113-8. PMID 9698219

[Tournilhac-3] Tournilhac O et al. Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood 2004;103:363-5. PMID 12969985

[Sneader-4] Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 258. ISBN 0-471-89979-8.

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fludarabine