Bendamustine is a highly effective chemotherapeutic agent that achieves better treatment results in certain types of cancer compared with conventional therapies (CHOP regimens). At the same time, it is associated with significantly fewer side effects than these. Most patients rate the hair loss, which occurs only rarely, as particularly positive.
What is bendamustine
Bendamustine is a highly effective chemotherapeutic agent that produces better treatment results in certain types of cancer compared with conventional therapies (CHOP regimens). Bendamustine (molecular formula: C16H21Cl2N3O2) exists as bendamustine hydrochloride in cancer drugs. Chemically, it belongs to the group of bifunctional alkylanzien and to the subgroup of nitrogen-lost derivatives. Compared with these, however, it causes far fewer side effects. Bendamustine is a cytostatic drug that deactivates tumor cells by alkylation. It inhibits tumor growth equally efficiently in hematologic 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 1960s in the GDR and first described scientifically in 1963. The physicians called it IMET3393. It was available as a drug at the end of the 1960s (trade name: Cytostasan). It was approved in the Federal Republic of Germany in 1993. The drug, which is effective within a few minutes, fights cancer cells much more efficiently than other members of its active substance group. It not only deactivates them, but also triggers their suicide program (apoptosis). In combination therapy with rituximab, even tumor cells that are resistant to alkylating agents and refractorily reactive are contained. The exact dosage of the drug is determined according to the clinical picture, degree of pretreatment and the size of the patient’s body surface. Bendamustine is available as a monopreparation under the trade names Levact and Ribomustine.
Pharmacologic Action
Bendamustine is markedly fast-acting: within about 7 minutes, it spreads to all body tissues regardless of the patient’s tumor stage or age. However, spread throughout the body does not occur uniformly. In the liver, it is immediately converted into the cytotoxic hydroxy derivative. Bendamustine has antineoplastic and anticytocidal effects. The active substance is metabolized in the liver. This produces the active metabolites M3 and M4, which, however, show much lower efficacy compared with the parent substance: M3 occurs in blood plasma at a concentration of about 1:10 compared with bendamustide, M4 at a ratio of 1:100. Bendamustide destroys the DNA of tumor cells by alkylation. It alters the DNA double strand by stimulating cross-linking of DNA and functional proteins. This results in double helix strand breaks and also chromosome strand breaks that cannot 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/proliferate and eventually dies. The repair of damaged tumor DNA is severely inhibited, especially in breast cancer. Bendamustine binds more than 90% to plasma proteins (albumin) after intravenous administration and is nevertheless excreted from the body within an average of 40 minutes. Nearly 95% of it is excreted through the urinary tract. Only about one-tenth of the administered drug is not metabolized by the body. They can be detected in the urine.
Medical use and application
Bendamustine is administered parenterally only. The dose selected, taking into account individual factors (age, type of cancer, tumor stage, prior treatment, body surface area), ranges from 50 to 150 mg/m² KOF. The drug 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 KOF), it can also be administered for up to 5 consecutive days. Advantageously, there is no cross-resistance to other cytostatic drugs with the use of bendamustine. The drug 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 has also been shown to be effective in the treatment of breast cancer – for which it was approved in the GDR – and small-cell bronchial carcinoma. For example, survival in indolent non-Hodgkin’s lymphoma and mantle cell lymphoma in later stages of cancer with combination therapy of bendamustine and rituximab compared with standard treatment (CHOP regimen) is approximately 70 to 31 months progression-free. 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 and side effects
Common side effects include leukocyte deficiency, anemia(anemia), myelosuppression, loss of appetite, nausea, hypersensitivity reactions, impaired sense of taste, dry mouth, colicky abdominal pain, heat sensations, redness of the face, mucosal irritation, diarrhea, constipation, and infection. In rarer cases, skin disorders, allergic reactions, and phlebitis at the injection site may occur. Hair loss (alopecia) is very rare and never affects the entire scalp. Nausea is also less common with treatment with bendamustine than with other cytostatic drugs. Nausea occurs with a time delay in about one-third of patients and is treated with a nausea-inhibiting agent (5HT3 antagonist). The tumor-inhibiting drug should not be used in cases of impaired kidney function, severe liver damage, altered blood count, jaundice, previous major surgery, yellow fever vaccination, infections, pregnancy and lactation (in animal studies, damage to the embryo occurred). Whether bendamustine crosses the placental barrier 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, and male patients should continue to use contraception for as long as 6 months after the last infusion.
