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Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkin's lymphoma.^[2]^[3] It is given by injection into a vein.^[2]

Common side effects include low blood cell counts, fever, nausea, diarrhea, loss of appetite, cough, and rash. Other severe side effects include allergic reactions and increased risk of infection. Use in pregnancy is known to harm the baby. Bendamustine is in the alkylating agents family of medication. It works by interfering with the function of DNA and RNA.^[2]

Bendamustine was approved for medical use in the United States in 2008.^[2] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.^[4] The cost in the United Kingdom for the NHS is about 275.81 pounds per 100 mg vial.^[3] It was originally made from nitrogen mustard.^[2]

Medical uses

Bendamustine has been used both as sole therapy and in combination with other agents including etoposide, fludarabine, mitoxantrone, methotrexate, prednisone, rituximab, vincristine and ⁹⁰Y-ibritumomab tiuxetan.^{[citation needed]}

Lymphomas

One combination for stage III/IV relapsed or refractory indolent lymphomas and mantle cell lymphoma (MCL), with or without prior rituximab-containing chemoimmunotherapy treatment, is bendamustine with mitoxantrone and rituximab.^[5] In Germany in 2012 it has become the first line treatment of choice for indolent lymphoma.^[6] after Trial results released in June 2012 showed that it more than doubled disease progression-free survival when given along with rituximab. The combination also left patients with fewer side effects than the older R-CHOP treatment.^[7]

Adverse effects

Common adverse reactions are typical for the class of nitrogen mustards, and include nausea, fatigue, vomiting, diarrhea, fever, constipation, loss of appetite, cough, headache, unintentional weight loss, difficulty breathing, rashes, and stomatitis, as well as immunosuppression, anemia, and low platelet counts. Notably, this drug has a low incidence of hair loss (alopecia) unlike most other chemotherapy drugs.^[8]

Warning

Bendamustine solution is not compatible with Closed System Transfer Devices (CSTD) Situation:

FDA issued a warning on March 11, 2015 not to use bendamustine solution with CSTDs, adapters and syringes which contain either polycarbonate or acrylonitrile-butadiene-styrene (ABS) due to the incompatibility with N,N-dimethylacetamide (DMA).

Background:

PhaSealR & SpirosR CSTDs contain either polycarbonate or ABS can dissolve when coming into contact with bendamustine (which contains DMA).

Assessment:

This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in health care professionals preparing and administering this product and the risk of small blood vessel blockage in patients.

Recommendations:

Immediately, stop using all PhaSealR &/or SpirosR products including adapters when preparing & administering bendamustine.
Only use polypropylene syringes with bendamustine. These syringes are translucent in appearance.
Continue to use all universal PPE & safety precautions for hazardous drugs when preparing & administering bendamustine.

Pharmacology

Bendamustine is a white, water-soluble microcrystalline powder with amphoteric properties. It acts as an alkylating agent causing intra-strand and inter-strand cross-links between DNA bases.

After intravenous infusion it is extensively metabolised in the liver by cytochrome p450. More than 95% of the drug is bound to protein - primarily albumin. Only free bendamustine is active. Elimination is biphasic with a half-life of 6–10 minutes and a terminal half-life of approximately 30 minutes. It is eliminated primarily through the kidneys.

History

Bendamustine was first synthesized in 1963 by Ozegowski and Krebs in East Germany (the former German Democratic Republic). Until 1990 it was available only in East Germany. East German investigators found that it was useful for treating chronic lymphocytic leukemia, Hodgkin’s disease, non-Hodgkin’s lymphoma, multiple myeloma and lung cancer.

Bendamustine received its first marketing approval in Germany, where it is marketed under the tradename Ribomustin, by Astellas Pharma GmbH's licensee, Mundipharma International Corporation Limited. It is indicated as a single-agent or in combination with other anti-cancer agents for indolent non-Hodgkin's lymphoma, multiple myeloma, and chronic lymphocytic leukemia. SymBio Pharmaceuticals Ltd. holds exclusive rights to develop and market bendamustine HCl in Japan and selected Asia Pacific Rim countries.

In March 2008, Cephalon received approval from the United States Food and Drug Administration to market bendamustine in the US, where it is sold under the tradename Treanda, for treatment of chronic lymphocytic leukemia.^[9]

In October 2008, the FDA granted further approval to market Treanda for the treatment of indolent B-cell non-Hodgkin's lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.^[10]

Research

It is also being studied for the treatment of sarcoma.^[11] It is also being investigated in phase II trials for the non-cancer treatment of AL amyloidosis.

References

^ Dubbelman AC, Rosing H, Darwish M, D'Andrea D, Bond M, Hellriegel E, Robertson P, Beijnen JH, Schellens JH (March 2013). "Pharmacokinetics and excretion of 14C-bendamustine in patients with relapsed or refractory malignancy". Drugs R D. 13: 17–28. doi:10.1007/s40268-012-0001-5. PMC 3627029. PMID 23322528.
^ ^a ^b ^c ^d ^e "Bendamustine Hydrochloride". The American Society of Health-System Pharmacists. Retrieved 8 December 2016.
^ ^a ^b British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 579. ISBN 9780857111562.
^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016.
^ Weide R, Hess G, Köppler H, et al. (2007). "High anti–lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A muticenter phase II study of the German Low Grade Lymphoma Study Group (GLSG)". Leuk. Lymphoma. 48 (7): 1299–1306. doi:10.1080/10428190701361828. PMID 17613757.
^ New Combo Replaces CHOP for Lymphoma. Dec 2012
^ "'Rediscovered' Lymphoma Drug Helps Double Survival: Study". June 3, 2012.
^ Tageja N, Nagi J (Aug 2010). "Bendamustine: something old, something new". Cancer Chemotherapy and Pharmacology. 66 (3): 413–23. doi:10.1007/s00280-010-1317-x.
^ "Cephalon press release - Cephalon Receives FDA Approval for TREANDA, a Novel Chemotherapy for Chronic Lymphocytic Leukemia". Retrieved 2008-03-23.
^ "Cephalon press release -Cephalon Receives FDA Approval for TREANDA to Treat Patients with Relapsed Indolent Non-Hodgkin's Lymphoma". Retrieved 2008-11-03.
^ Bagchi S (August 2007). "Bendamustine for advanced sarcoma". Lancet Oncol. 8 (8): 674. doi:10.1016/S1470-2045(07)70225-5. PMID 17726779.

External links

Manufacturer's website (US)

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. マントル細胞リンパ腫の初期治療 initial treatment of mantle cell lymphoma
3. 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
4. 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
5. 再発性または難治性の慢性リンパ性白血病の治療 treatment of relapsed or refractory chronic lymphocytic leukemia

English Journal

New patterns of relapse in multiple myeloma: a case of "light chain escape" in which FLC predicted relapse earlier than urine and serum immunofixation.

Caldini A, Nozzoli C, Terreni A, Staderini M, Berardi M, Biagioli T, Brogi M, Bosi A.
Clinical chemistry and laboratory medicine.Clin Chem Lab Med.2016 Jun 1;54(6):991-5. doi: 10.1515/cclm-2015-0689.
Multiple myeloma (MM) is characterized, in about 80% of cases, by the production of monoclonal intact immunoglobulin and more than 95% of them have elevated concentrations of involved (i.e. of the same class of intact immunoglobulin) free light chain (FLC). The introduction of novel therapeutic stra
PMID 26581069

Is There a Best Initial Treatment for a New Patient With Low Grade Follicular Lymphoma.

Jacobson CA1, Freedman AS2.
Current hematologic malignancy reports.Curr Hematol Malig Rep.2016 Jun;11(3):218-23. doi: 10.1007/s11899-016-0321-6.
The treatment landscape for newly diagnosed follicular lymphoma (FL) has dramatically changed over the past decade, first with the advent of rituximab and then with the activity of old and new drugs, like bendamustine and lenalidomide, in this disease. The efficacy and tolerability of rituximab has
PMID 26995595

Combination of bendamustine and rituximab as front-line therapy for patients with chronic lymphocytic leukaemia: multicenter, retrospective clinical practice experience with 279 cases outside of controlled clinical trials.

Gentile M1, Zirlik K2, Ciolli S3, Mauro FR4, Di Renzo N5, Mastrullo L5, Angrilli F6, Molica S7, Tripepi G8, Giordano A9, Di Raimondo F10, Selleri C11, Coscia M12, Musso M13, Orsucci L14, Mannina D15, Rago A16, Giannotta A17, Ferrara F18, Herishanu Y19, Shvidel L20, Tadmor T21, Scortechini I22, Ilariucci F23, Murru R24, Guarini A25, Musuraca G26, Mineo G27, Vincelli I28, Arcari A29, Tarantini G30, Caparrotti G31, Chiarenza A10, Levato L6, Villa MR32, De Paolis MR5, Zinzani PL33, Polliack A34, Morabito F35.
European journal of cancer (Oxford, England : 1990).Eur J Cancer.2016 Jun;60:154-65. doi: 10.1016/j.ejca.2016.03.069. Epub 2016 Apr 27.
Recently, encouraging results in terms of safety and efficacy have been obtained using bendamustine-rituximab (BR) in untreated chronic lymphocytic leukaemia (CLL) patients enrolled in a phase II study. Here, we report a retrospective international multicenter study of CLL patients treated with BR a
PMID 27127905

Japanese Journal

マクログロブリン血症および類縁疾患の治療 : IWWM-7コンセンサス

旭真来,伊藤薫樹
血液内科 = Hematology 70(6), 774-780, 2015-06
NAID 40020529918

本邦において推奨されるベンダムスチン投与法と支持療法

大間知謙
血液内科 70(1), 77-81, 2015-01
NAID 40020341673

Magnifying Endoscopic Observation of Duodenal Involvement of Follicular Lymphoma before and after Chemotherapy

Iwamuro Masaya,Okada Hiroyuki,Takata Katsuyoshi,Fujii Nobuharu,Kawano Seiji,Kawahara Yoshiro,Yoshino Tadashi,Yamamoto Kazuhide
Internal Medicine 54(14), 1741-1745, 2015
… Chemotherapy with bendamustine and rituximab was administered, and complete remission was confirmed by CT scanning and positron emission tomography scanning. …
NAID 130005088253

Related Pictures

Bendamustine, Thalidomide and Dex: Viable Salvage Option for Double-Relapsed Bendamustine in B-Cell Malignancies: The New 46-Year-Old Kid on the Block | Clinical Bendamustine anti-cancer drug - Stock Image C011/5418 - Science Photo Library TREANDA (Cephalon, Incorporated): FDA Package Insert, Page 8 BENDAMUSTINE ACCORD - PRODUKTY INIEKCYJNE – produkty farmaceutyczne firmy Accord MODERN TIME HELPLINES PHARMA - Exporter, Distributor & Supplier, Delhi, India A Pastor's Cancer Diary: July 13, 2010 – Bendamustine Rising Bendamustine Injection, Exporter,Supplier,Wholesaler, Price India | 3S Corporation

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「ベンダムスチン」

Bendamustine
Clinical data
Trade names	Treanda, Treakisym, Ribomustin, Levact, others
AHFS/Drugs.com	Monograph
MedlinePlus	a608034
License data	US FDA: Treanda;
Pregnancy; category	US: D (Evidence of risk); ;
Routes of; administration	intravenous infusion
ATC code	L01AA09 (WHO);
Legal status
Legal status	US: ℞-only;
Pharmacokinetic data
Bioavailability	NA (intravenous only)
Protein binding	94–96%
Metabolism	Hydrolyzed to inactive metabolites. Two minor metabolites (M3 and M4) formed by CYP1A2
Biological half-life	40 min (bendamustine), 3 h (M3), 30 min (M4)
Excretion	~50% urinary, ~25% fecal
Identifiers
	IUPAC name 4-[5-[Bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoic acid;
Synonyms	SDX-105
CAS Number	16506-27-7 ;
PubChem CID	65628;
IUPHAR/BPS	7478;
ChemSpider	59069 ;
UNII	9266D9P3PQ;
ChEMBL	CHEMBL487253 ;
ECHA InfoCard	100.205.789
Chemical and physical data
Formula	C16H21Cl2N3O2
Molar mass	358.262 g/mol
3D model (Jmol)	Interactive image;
	SMILES ClCCN(c2ccc1c(nc(n1C)CCCC(=O)O)c2)CCCl ;
	InChI InChI=1S/C16H21Cl2N3O2/c1-20-14-6-5-12(21(9-7-17)10-8-18)11-13(14)19-15(20)3-2-4-16(22)23/h5-6,11H,2-4,7-10H2,1H3,(H,22,23) ; Key:YTKUWDBFDASYHO-UHFFFAOYSA-N ;
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　　[★]

英: bendamustine
商: トレアキシン
関: アルキル化剤

[1] Dubbelman AC, Rosing H, Darwish M, D'Andrea D, Bond M, Hellriegel E, Robertson P, Beijnen JH, Schellens JH (March 2013). "Pharmacokinetics and excretion of 14C-bendamustine in patients with relapsed or refractory malignancy". Drugs R D. 13: 17–28. doi:10.1007/s40268-012-0001-5. PMC 3627029. PMID 23322528.

[AHFS2016-2] "Bendamustine Hydrochloride". The American Society of Health-System Pharmacists. Retrieved 8 December 2016.

[BNF69-3] British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 579. ISBN 9780857111562.

[WHO19th-4] "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016.

[Weide2007-5] Weide R, Hess G, Köppler H, et al. (2007). "High anti–lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A muticenter phase II study of the German Low Grade Lymphoma Study Group (GLSG)". Leuk. Lymphoma. 48 (7): 1299–1306. doi:10.1080/10428190701361828. PMID 17613757.

[6] New Combo Replaces CHOP for Lymphoma. Dec 2012

[7] "'Rediscovered' Lymphoma Drug Helps Double Survival: Study". June 3, 2012.

[8] Tageja N, Nagi J (Aug 2010). "Bendamustine: something old, something new". Cancer Chemotherapy and Pharmacology. 66 (3): 413–23. doi:10.1007/s00280-010-1317-x.

[9] "Cephalon press release - Cephalon Receives FDA Approval for TREANDA, a Novel Chemotherapy for Chronic Lymphocytic Leukemia". Retrieved 2008-03-23.

[10] "Cephalon press release -Cephalon Receives FDA Approval for TREANDA to Treat Patients with Relapsed Indolent Non-Hodgkin's Lymphoma". Retrieved 2008-11-03.

[11] Bagchi S (August 2007). "Bendamustine for advanced sarcoma". Lancet Oncol. 8 (8): 674. doi:10.1016/S1470-2045(07)70225-5. PMID 17726779.

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