Active Ingredients

Bendamustine – Effect, Application & Risks

Bendamustine

Bendamustine is a highly effective chemotherapeutic agent that achieves better treatment outcomes in certain types of cancer compared to conventional therapies (CHOP regimen) . At the same time, it is associated with significantly fewer side effects than these. Most of those affected rate the rarely occurring hair loss as positive.

What is bendamustine

Bendamustine (molecular formula: C16H21Cl2N3O2) is present as bendamustine hydrochloride in cancer drugs. Chemically, it belongs to the group of bifunctional alkylating agents and to the subgroup of nitrogen mustard derivatives. However, compared to these, it causes far fewer side effects.

Bendamustine is a cytostatic that deactivates tumor cells by means of alkylation . It inhibits tumor growth equally efficiently in hematological and solid tumors. Bendamustine is used either as a mono preparation or together with the monoclonal antibody rituximab .

The active ingredient was developed in the GDR in the 1960s and scientifically described for the first time in 1963. The medics dubbed it IMET3393. It was available as a drug in the late 1960s (trade name: Cytostasan®). It was approved in Germany in 1993.

The drug, which takes effect within a few minutes, fights cancer cells much more efficiently than other members of its active ingredient group. Not only does it disable them, but it also triggers their suicide program ( apoptosis ). In combination therapy with rituximab, even tumor cells that are resistant to and refractory to alkylating agents are contained.

The exact dosage of the agent depends on the clinical picture, the degree of previous treatment and the size of the patient’s body surface. Bendamustine is available as a mono preparation under the trade names Levact® and Ribomustine®.

Pharmacological action

Bendamustine works extremely quickly: It is distributed in all body tissues within about 7 minutes, regardless of the tumor stage and age of the patient. However, the spread in the body does not happen uniformly everywhere. In the liver it is immediately converted into the cytotoxic hydroxy derivative. Bendamustine has an antineoplastic and anticytocidal effect. The active ingredient is metabolized in the liver . This produces the active metabolites M3 and M4, which, however – compared to the parent substance – show a significantly lower effectiveness: M3 occurs in the blood plasma in a concentration of about 1:10 compared to bendamustine, M4 in a ratio of 1:100.Bendamustide destroys the DNA of tumor cells by alkylation. It changes the DNA double strand by stimulating the cross-linking of DNA and functional proteins. This results in double helix strand breaks and chromosomal strand breaks that can no longer be repaired. The cancer cell mutates and its functionality is disrupted. The damaged genetic information can no longer be read and transcribed. As a result, the degenerated cell can no longer divide/multiply and eventually dies. The repair of damaged tumor DNA is severely inhibited , especially in breast cancer .

After intravenous administration, bendamustine is more than 90% bound to plasma proteins (albumin) and is nevertheless excreted from the body within an average of 40 minutes. Almost 95% of it is eliminated via the urinary tract . Only about a tenth of the administered active ingredient is not metabolized by the body. They can be detected in the urine .

Medical Application & Use

Bendamustine is administered parenterally only. The selected dose is between 50 and 150 mg/m² body surface area, taking into account individual factors (age, type of cancer, tumor stage, previous treatment, size of the body surface). The remedy is usually applied as a short-term infusion (30 to 60 minutes) on two consecutive days. Chemotherapy is repeated every 4 weeks. At lower doses (50 to 60 mg/m² BSA) it can also be administered on up to 5 consecutive days.

It is advantageous that taking bendamustine does not lead to cross-resistance to other cytostatics. The agent is approved for the treatment of Hodgkin’s disease , multiple myeloma , mantle cell lymphoma, indolent non-Hodgkin’s lymphoma and chronic lymphocytic leukemia (CLL).

However, bendamustine is also proven to be effective in the treatment of breast cancer – it was approved for this in the GDR – and in small cell bronchial carcinoma . For example, the survival time in indolent non-Hodgkin’s lymphoma and mantle cell lymphoma in later cancer stages with the combination therapy of bendamustine and rituximab compared with the standard treatment (CHOP regimen) progression-free is about 70 to 31 months. When CHOP was administered, tumor growth progressed, albeit inhibited.

Bendamustine is not effective in melanoma , germ cell tumors , soft tissue sarcoma, liver carcinoma , bile duct carcinoma and squamous cell carcinoma of the head and neck.

Risks & side effects

Common side effects include leukocyte deficiency, anemia (low blood count), myelosuppression , loss of appetite , nausea , hypersensitivity reactions, impaired sense of taste, dry mouth , colicky abdominal pain , flushing , facial redness , irritation of the mucous membranes , diarrhea , constipation and infection . In rarer cases, it can cause skin disorders , allergic reactions and phlebitisarrive at the injection site.Hair loss (alopecia) is very rare and never affects the entire scalp. Nausea is also less common during treatment with bendamustine than with other cytostatics. The nausea occurs with a delay in about a third of the patients and is treated with an anti-nausea agent (5HT3 antagonist).

The tumor-inhibiting drug should not be used in the case of impaired kidney function, severe liver damage, altered blood count , jaundice , previous serious operations, yellow fever vaccination, infections, pregnancy and lactation (animal experiments damaged the embryo). Whether bendamustine crosses the placenta or passes into breast milk has not yet been determined in humans.

Patients of sexually active age should use effective contraception during their chemotherapy with bendamustine, male patients even up to 6 months after the last infusion .

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.