Cheson Bruce D, Leoni Lorenzo
Division of Hematology-Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC, USA.
Clin Adv Hematol Oncol. 2011 Aug;9(8 Suppl 19):1-11.
Bendamustine is a chemotherapeutic agent that displays a unique pattern of cytotoxicity compared with conventional alkylating agents. Bendamustine was originally synthesized in the former East German Democratic Republic in the 1960s. It was designed to have both alkylating and antimetabolite properties. The alkylating agent properties are similar to those seen with cyclophosphamide, chlorambucil, and melphalan, and the benzimidazole ring is similar to cladribine. Molecular analyses have revealed that bendamustine differs from other alkylating agents in its mechanism of action. Differences have been observed in regard to its effects on DNA repair and cell cycle progression. Moreover, bendamustine can induce cell death through both apoptotic and nonapoptotic pathways, thereby retaining activity even in cells without a functional apoptotic pathway. Bendamustine has demonstrated significant efficacy in patients with indolent lymphomas and chronic lymphocytic leukemia (CLL), including in patients with disease refractory to conventional alkylating agents and rituximab. The toxicity profile of bendamustine is also superior to that of conventional alkylating agents. Combination therapy with bendamustine and rituximab has demonstrated superior efficacy to a standard rituximab-containing chemotherapy regimen in patients with previously untreated indolent B-cell non-Hodgkin lymphoma, and it is currently being compared against the standard first-line regimen in CLL: fludarabine, cyclophosphamide, and rituximab. Ongoing and planned studies are evaluating new strategies in which bendamustine is being combined with existing agents and with novel therapies to optimize use in different clinical settings.
苯达莫司汀是一种化疗药物，与传统烷化剂相比，它具有独特的细胞毒性模式。苯达莫司汀最初于20世纪60年代在前东德民主共和国合成。它被设计成具有烷化和抗代谢特性。其烷化剂特性类似于环磷酰胺、苯丁酸氮芥和美法仑，而苯并咪唑环类似于克拉屈滨。分子分析表明，苯达莫司汀在作用机制上与其他烷化剂不同。在其对DNA修复和细胞周期进程的影响方面已观察到差异。此外，苯达莫司汀可通过凋亡和非凋亡途径诱导细胞死亡，从而即使在没有功能性凋亡途径的细胞中也能保持活性。苯达莫司汀已在惰性淋巴瘤和慢性淋巴细胞白血病（CLL）患者中显示出显著疗效，包括对传统烷化剂和利妥昔单抗耐药的患者。苯达莫司汀的毒性特征也优于传统烷化剂。在既往未治疗的惰性B细胞非霍奇金淋巴瘤患者中，苯达莫司汀与利妥昔单抗联合治疗已显示出优于含利妥昔单抗的标准化疗方案的疗效，目前正在与CLL的标准一线方案：氟达拉滨、环磷酰胺和利妥昔单抗进行比较。正在进行和计划中的研究正在评估新策略，即将苯达莫司汀与现有药物和新疗法联合使用，以优化在不同临床环境中的应用。
