Leonard John P, Furman Richard R, Coleman Morton
Division of Hematology and Medical Oncology, Center for Lymphoma and Myeloma, Weill Medical College of Cornell University and New York Presbyterian Hospital, NY 10021, USA.
Int J Cancer. 2006 Sep 1;119(5):971-9. doi: 10.1002/ijc.21805.
The incidence of non-Hodgkin's lymphoma (NHL) has markedly increased in the US and other westernized countries in recent years and presents a considerable clinical challenge. NHL is divided into subtypes that follow an aggressive or indolent course. Follicular lymphoma (FL), the most common indolent subtype, and mantle cell lymphoma (MCL), an aggressive subtype that accounts for approximately 5% of cases, are generally incurable. MCL has a relatively poor prognosis, with a median survival of 3-4 years. Despite improving response rates with new agents and regimens, the lack of demonstrated improvement in overall survival in many subtypes supports the development of novel approaches, such as proteasome inhibition. Bortezomib is the first proteasome inhibitor to be evaluated in human studies. It has already been approved as second-line treatment in multiple myeloma and is now under active investigation in NHL. The US FDA has granted bortezomib fast-track designation for relapsed and refractory MCL. In vitro and in vivo studies have demonstrated single-agent activity against various lymphoid tumors, and additive or synergistic effects in combination with other agents, including standard chemotherapy drugs employed in NHL. Phase 2 clinical trials indicate that bortezomib is well tolerated and active in several NHL subtypes, with response rates of 18-60% in FL and 39-56% in MCL. A number of combination trials are currently underway with a range of standard agents. Bortezomib has the potential to play a significant role throughout the NHL treatment algorithm in the future.
近年来，非霍奇金淋巴瘤（NHL）在美国和其他西方国家的发病率显著上升，这带来了相当大的临床挑战。NHL可分为侵袭性或惰性病程的亚型。滤泡性淋巴瘤（FL）是最常见的惰性亚型，而套细胞淋巴瘤（MCL）是一种侵袭性亚型，约占病例的5%，通常无法治愈。MCL的预后相对较差，中位生存期为3至4年。尽管新药物和治疗方案提高了缓解率，但许多亚型的总生存期缺乏明显改善，这支持了开发新方法，如蛋白酶体抑制。硼替佐米是第一种在人体研究中进行评估的蛋白酶体抑制剂。它已被批准作为多发性骨髓瘤的二线治疗药物，目前正在NHL中进行积极研究。美国食品药品监督管理局（FDA）已授予硼替佐米用于复发和难治性MCL的快速通道指定。体外和体内研究表明，硼替佐米对各种淋巴瘤具有单药活性，与其他药物（包括NHL中使用的标准化疗药物）联合使用时具有相加或协同作用。2期临床试验表明，硼替佐米耐受性良好，在几种NHL亚型中具有活性，FL的缓解率为18%至60%，MCL的缓解率为39%至56%。目前正在进行一系列与多种标准药物的联合试验。硼替佐米未来有可能在整个NHL治疗方案中发挥重要作用。
