Bendamustine, sold under the brand name Treanda among others, is a

chemotherapy medication Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothera ...

used in the treatment of chronic lymphocytic leukemia (CLL),

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, an ...

, and

non-Hodgkin's lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of hematological malignancy, blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include lymphadenopathy, enlarged lymph nodes, fever ...

. It is given by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutri ...

. Common side effects include low blood cell counts, fever, nausea,

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...

, loss of appetite, cough, and rash. Other severe side effects include

allergic reactions Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

and increased risk of infection. Use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

is known to harm the baby. Bendamustine is in the

alkylating agent Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...

s family of medication. It works by interfering with the function of DNA and

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

. Bendamustine was approved for medical use in the United States in 2008. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. The cost in the United Kingdom for the

NHS The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...

is about 275.81 pounds per 100 mg vial. It was originally made from nitrogen mustard.

Medical uses

Bendamustine has been used both as sole therapy and in combination with other agents including

etoposide Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is ...

fludarabine Fludarabine is a purine analogue and antineoplastic agent. It is generally used as its 5-O-phosphorylated form known as fludarabine phosphate, sold under the brand name Fludara among others. It is a chemotherapy medication used in the treatmen ...

, mitoxantrone,

methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...

prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...

rituximab Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in non-geriatric pa ...

vincristine Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...

and ⁹⁰Y-

ibritumomab tiuxetan Ibritumomab tiuxetan (pronounced ), sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for non-Hodgkin's lymphoma. The drug uses the monoclonal mouse IgG1 antibody ibritumomab in conjunction with the chelator ...

Lymphomas

One combination for stage III/IV relapsed or refractory indolent

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

s and

mantle cell lymphoma Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the United States with mantle cell lymphoma. It is named for the mantle zone of the lymph n ...

(MCL), with or without prior rituximab-containing chemoimmunotherapy treatment, is bendamustine with mitoxantrone and rituximab. In Germany in 2012 it has become the first line treatment of choice for indolent lymphoma. After trial results released in June 2012 showed that it more than doubled disease

progression-free survival Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is p ...

when given along with

. The combination also left patients with fewer side effects than the older R-CHOP treatment.

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 Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration. In its widest meaning, stomatitis can have a multitude of different cau ...

, as well as immunosuppression, anemia, and low platelet counts. Notably, this drug has a low incidence of hair loss (

alopecia Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scar ...

) unlike most other chemotherapy drugs.

Warning

Bendamustine solution is not compatible with Closed System Transfer Devices (CSTD) Situation: *Most CSTD vendors have adapted their system to become compatible. * 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 In chemistry, an amphoteric compound () is a molecule or ion that can react both as an acid and as a base. What exactly this can mean depends on which definitions of acids and bases are being used. One type of amphoteric species are amphiproti ...

properties. It acts as an

causing intra-strand and inter-strand cross-links between DNA bases. After intravenous infusion it is extensively metabolised in the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

cytochrome p450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

. More than 95% of the drug is bound to protein – primarily

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

. 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

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

History

Bendamustine was first made in 1963 by Ozegowski and Krebs in

East Germany East Germany, officially the German Democratic Republic (GDR; german: Deutsche Demokratische Republik, , DDR, ), was a country that existed from its creation on 7 October 1949 until its dissolution on 3 October 1990. In these years the state ...

(the former German Democratic Republic). Until 1990 it was available only in East Germany. East German researchers found that it was useful for treating chronic lymphocytic leukemia, Hodgkin's disease,

and

lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...

. 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

, 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 The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

to market bendamustine in the US, where it is sold under the tradename Treanda, for treatment of chronic lymphocytic leukemia. 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.

Research

It is also being studied for the treatment of

sarcoma A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal (connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarcom ...

. It is also being investigated in phase II trials for the non-cancer treatment of

AL amyloidosis Amyloid light-chain (AL) amyloidosis, also known as primary amyloidosis, is the most common form of systemic amyloidosis in the US. The disease is caused when a person's antibody-producing cells do not function properly and produce abnormal protein ...

References

External links

* {{portal bar, Medicine Benzimidazoles Organochlorides Nitrogen mustards Chloroethyl compounds World Health Organization essential medicines Wikipedia medicine articles ready to translate Science and technology in East Germany