Bendamustine: A Novel Cytotoxic Agent for Hematologic Malignancies

Abstract

A significant need exists for effective and well-tolerated treatments for patients with hematologic malignancies. Bendamustine hydrochloride is a novel cytotoxic agent that possesses alkylator and purine-like structural groups, which may confer a unique mechanism of action. Bendamustine recently was approved by the U. S. Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL) and currently is being used in clinical trials for a number of hematologic and solid tumors. Bendamustine has demonstrated promising clinical activity in patients with hematologic malignancies and has manageable toxicities when administered as monotherapy or in combination with other agents. In clinical trials, nausea, fatigue, vomiting, fever, diarrhea, constipation, and headache were the most commonly reported nonhematologic side effects. Reversible myelosuppression also was reported. Nurses need to understand the efficacy and safety profiles of bendamustine to educate patients and their families about its use and expected side effects. Knowledge of specific measures for preventing and managing associated side effects and dose modifications is integral to the provision of optimal care.

The first-in-class alkylating deacetylase inhibitor molecule tinostamustine shows antitumor effects and is synergistic with radiotherapy in preclinical models of glioblastoma

“…Bendamustine (BDM) is an alkylating chemotherapeutic agent displaying a unique pattern of cytotoxicity compared with TMZ [ 9 ]. This is a bifunctional mechlorethamine derivative with properties similar to those seen with cyclophosphamide, chlorambucil, and melphalan, containing a purine-like benzimidazole ring similar to cladribine.…”

“…Moreover, BDM can induce cell death through both apoptotic and non-apoptotic pathways, thereby retaining activity even in cells without a functional apoptotic pathway. BDN appears to have only a partial cross resistance to other alkylating agents [ 9 – 11 ] and was used as a salvage therapy monotherapy for recurrent GBM [ 12 ]. Histone deacetylases (HDAC) are frequently overexpressed in tumors including GBMs [ 13 ] and control the gene expression, cell proliferation, and drug resistance of tumor cells [ 14 ].…”

Management of Cytotoxic Extravasation - ASORS Expert Opinion for Diagnosis, Prevention and Treatment

“…Tolerability can be augmented by higher dilution or prolonged infusion time [30]. In the case of bendamustine, an incidence of 35% has been reported for phlebitis, which is thought to be caused by low pH values due to low dilution [31]. Inflammation and pain following intravenous administration of busulfan have also been attributed to its low pH value of 3.4-3.9.…”

A Canadian Perspective on the Safe Administration of Bendamustine and the Prevention and Management of Adverse Events

“…The most common hematologic toxicities with bendamustine in cll and inhl are neutropenia, thrombocytopenia, and anemia (Table iv) 19 . In addition, the frequency of neutropenia tends to increase after cycle 3 and is generally higher in patients more than 65 years of age.…”

“…Although irrs can occur during any treatment cycle, they are more frequent after cycle 2. They can be effectively managed by prophylactic treatment, careful monitoring of symptoms, and patient education 18,19 . Because bendamustine is administered over a 2-day period, management with acetaminophen and diphenhydramine before each day's infusion is recommended (Table iii).…”