Bendamustine

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Bendamustine
Bendamustine.png
Systematic (IUPAC) name
4-[5-[Bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoic acid
Clinical data
Trade names Treanda
AHFS/Drugs.com Consumer Drug Information
MedlinePlus a608034
Licence data US FDA:link
Pregnancy cat. D (US)
Legal status -only (US)
Routes Intravenous infusion
Pharmacokinetic data
Bioavailability NA (intravenous only)
Protein binding 94–96%
Metabolism Hydrolyzed to inactive metabolites. Two minor metabolites (M3 and M4) formed by CYP1A2
Half-life 40 min (bendamustine), 3 h (M3), 30 min (M4)
Excretion Mostly fecal
Identifiers
CAS number 16506-27-7 YesY
ATC code L01AA09
PubChem CID 65628
ChemSpider 59069 YesY
UNII 9266D9P3PQ YesY
ChEMBL CHEMBL487253 YesY
Chemical data
Formula C16H21Cl2N3O2 
Mol. mass 358.262 g/mol
 YesY (what is this?)  (verify)

Bendamustine (INN, trade names Treakisym, Ribomustin, Levact and Treanda; also known as SDX-105) is a nitrogen mustard used in the treatment of chronic lymphocytic leukemia[1] and lymphomas. It belongs to the family of drugs called alkylating agents. It is also being studied for the treatment of sarcoma.[2]

History[edit]

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.[3]

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.[4]

Pharmacology[edit]

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. This paragraph is inconsistent with sidebar for primary excretion pathway.

Chemotherapeutic uses[edit]

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[edit]

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[edit]

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]

References[edit]

  1. ^ Kath R, Blumenstengel K, Fricke HJ, Höffken K (January 2001). "Bendamustine monotherapy in advanced and refractory chronic lymphocytic leukemia". J. Cancer Res. Clin. Oncol. 127 (1): 48–54. doi:10.1007/s004320000180. PMID 11206271. 
  2. ^ Bagchi S (August 2007). "Bendamustine for advanced sarcoma". Lancet Oncol. 8 (8): 674. doi:10.1016/S1470-2045(07)70225-5. PMID 17726779. 
  3. ^ "Cephalon press release - Cephalon Receives FDA Approval for TREANDA, a Novel Chemotherapy for Chronic Lymphocytic Leukemia". Retrieved 2008-03-23. 
  4. ^ "Cephalon press release -Cephalon Receives FDA Approval for TREANDA to Treat Patients with Relapsed Indolent Non-Hodgkin's Lymphoma". Retrieved 2008-11-03. 
  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, Nishant; Nagi, Jasdeepa; "Bendamustine: something old, something new"; Cancer Chemotherapy and Pharmacology, 2010 Aug;66(3):413-23. doi: 10.1007/s00280-010-1317-x.

External links[edit]