Anjana Elefante1, Myron S Czuczman. 1. Department of Pharmacy, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. angie.elefante@roswellpark.org
Abstract
PURPOSE: The pharmacology, efficacy, safety, and dosage and administration of bendamustine and its use in indolent non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are reviewed. SUMMARY: Bendamustine is an alkylating agent that has a unique, multifaceted mechanism of action. Compared with other alkylators, bendamustine produces more-extensive and long-lasting DNA damage. Bendamustine also inhibits cell-cycle checkpoints, leading to mitotic catastrophe and apoptosis. Bendamustine is approved for the treatment of CLL and for indolent B-cell NHL that has progressed during or within 6 months of treatment with rituximab or a rituximab-based regimen. In Phase II and III trials in patients with indolent NHL and CLL, bendamustine has demonstrated response rates of 67-84% as a single agent and median durations of response of 7-21 months. Additional clinical trials are examining bendamustine as a single agent and in combination therapy for the treatment of hematologic malignancies and solid tumors. Adverse events associated with bendamustine are typically mild to moderate and can usually be managed with supportive care. Myelosuppression is the most common grade 3 or 4 adverse event. Tumor lysis syndrome has been reported to occur in some patients, and preventive measures should be taken in at-risk patients. The dosage and administration differ for the treatment of NHL and CLL. CONCLUSION: Bendamustine is a well- tolerated and effective chemotherapeutic agent indicated for the treatment of rituximab-refractory, indolent NHL and CLL. It has demonstrated efficacy in patients whose disease is refractory to other therapies, including other alkylating agents.
PURPOSE: The pharmacology, efficacy, safety, and dosage and administration of bendamustine and its use in indolent non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are reviewed. SUMMARY:Bendamustine is an alkylating agent that has a unique, multifaceted mechanism of action. Compared with other alkylators, bendamustine produces more-extensive and long-lasting DNA damage. Bendamustine also inhibits cell-cycle checkpoints, leading to mitotic catastrophe and apoptosis. Bendamustine is approved for the treatment of CLL and for indolent B-cell NHL that has progressed during or within 6 months of treatment with rituximab or a rituximab-based regimen. In Phase II and III trials in patients with indolent NHL and CLL, bendamustine has demonstrated response rates of 67-84% as a single agent and median durations of response of 7-21 months. Additional clinical trials are examining bendamustine as a single agent and in combination therapy for the treatment of hematologic malignancies and solid tumors. Adverse events associated with bendamustine are typically mild to moderate and can usually be managed with supportive care. Myelosuppression is the most common grade 3 or 4 adverse event. Tumor lysis syndrome has been reported to occur in some patients, and preventive measures should be taken in at-risk patients. The dosage and administration differ for the treatment of NHL and CLL. CONCLUSION:Bendamustine is a well- tolerated and effective chemotherapeutic agent indicated for the treatment of rituximab-refractory, indolent NHL and CLL. It has demonstrated efficacy in patients whose disease is refractory to other therapies, including other alkylating agents.
Authors: Sean Warsch; Peter J Hosein; Michele I Morris; Uygar Teomete; Ronald Benveniste; Jennifer R Chapman; Izidore S Lossos Journal: Int J Hematol Date: 2012-06-09 Impact factor: 2.490