Treatment with Bendamustine
Patients with CLL do not always need treatment. CLL is usually diagnosed in older patients (median age 64 years). In some patients, perhaps a third, CLL never really progresses. These patients live for many years and die from another cause. In another group of patients the disease starts of slowly and then worsens, necessitating treatment. In the last group, CLL is immediately aggressive and treatment must be started as soon as the diagnosis is made.
There are staging systems to help decide whether or not a patient needs treatment. For the study that led to FDA approval of bendamustine, only CLL patients who definitely needed treatment were included. The patients had symptoms including, for example, not enough red blood cells, weight loss of 10% or more, severe night sweats, fever 100.5 or higher, bulky lymphadenopathy (large lymph nodes) or progressive disease.
The patients were treated with either chlorambucil, a well-known alkylating agent, or bendamustine. 59% of the patients taking bendamustine responded to the treatment, versus 26% of the patients taking chlorambucil. 8% of those taking bendamustine had complete disappearance of the cancer versus less than 1% of those taking chlorambucil.
However, 89% of the patients taking bendamustine suffered serious side effects, whereas those taking chlorambucil had 79%. More than 15% suffered from fever, neutropenia (low neutrophil count), thromobocytopenia (low platelet count), leucopenia (low white blood cells), nausea, vomiting, and anemia. More patients treated with bendamustine needed blood transfusions. Patients on bendamustine dropped out of the study most frequently because of hypersensitivity (allergy) or high fever. There was no significant difference in the number of deaths in the two groups.
For non-Hodgkin's lymphoma (NHL), bendamustine is also administered by injection. Cephalon reports that the drug stopped progression of this slow-growing cancer for a median on 9.3 months in a clinical trial.
The FDA approved bendamustine only for CLL and indolent non-Hodgkin's lymphoma at this time. It is manufactured in the Netherlands for Cephalon, Inc. It has not been proven to be better first-line treatment for CLL relative to any treatment except chlorambucil. The ongoing studies ongoing in Europe and the United States may clarify how bendamustine might be used to treat other malignancies.
Physicians prescribing the drug must follow the proper protocols. The recommended dose of bendamustine is 100 mg/meter squared, given intravenously on day one and day two of a 28 day cycle, for a total of up to 6 cycles. Bendamustine comes as a single-use vial containing 100 mg of the drug as a lyophilized powder. It must first be mixed with 20 milliliters of Sterile Water. It is now at a concentration of 5mg/mL. The amount determined for treatment must then be mixed with 5000 mL of 0.9% Sodium Chloride Injection (normal saline) and then given to the patient intravenously over a 30 minute period. If during any of the preparation, particulate matter is observed, the product cannot be used. Once mixed it can be stored for 24 in a refrigerator or up to 3 hours at room temperature and in light.
Bendamustine comes with warnings about serious adverse reaction. It may cause myelosuppression, in which not enough blood cells are made. These may necessitate stopping the drug, and monitoring the blood cells. Treatment may be tried again if the blood cells recover. Signs of infection and fever need immediate aggressive treatment. Allergy to the drug can be mild or severe, including anaphylactic reactions. The drug should not be used if there has been a severe reaction. For milder reactions, patients can be pretreated with antihistamines, steroids, and antipyretics before the next dose. Tumor lysis syndrome, in which the large amount of dying tumor cells flood the body and kidneys can occur. This can cause kidney failure and death. Using allopurinol for patients at risk for the syndrome is recommended. Severe skin reactions can occur. Bendamustine should never be used during pregnancy.
The treatment protocol for bendamustine tells doctors when to withhold the medication and how to handle the adverse reactions. There are also instructions for how to modify doses in patients with poor liver or kidney function.
As a bifunctional mechlorethamine derivative, bendamustine was created explicitly to combine alkylating properties of mechlorethamine and the purine antimetabolite properties of benzimidazole.