Hernandez-Ilizaliturri Francisco J, Gowda Aruna, Czuczman Myron S
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Clin Adv Hematol Oncol. 2004 Sep;2(9):606-18.
The design of innovative, more effective, and less toxic therapy of B-cell lymphoma is emerging in parallel to a better understanding of the mechanisms of action of target-specific agents targeting the neoplastic B cell. Rituximab has changed the treatment paradigm of patients with B-cell lymphomas and is considered the first effective targeted therapy approved by the US Food and Drug Administration (FDA) for the treatment of lymphoproliferative disorders. Despite its good efficacy and safety profile, sustained complete remissions have been documented in a relatively small proportion of patients treated with rituximab monotherapy. To improve antitumor activity, initial strategies combined rituximab with standard chemotherapy drugs which led to higher response rates and improvement in disease-free and in some cases (ie, diffuse large B-cell lymphoma) prolongation of overall survival. While rituximab has been incorporated into multiple chemotherapy regimens (ie, CVP, CHOP, FND, etc.) a significant number of lymphoma patients either relapse after initial responses or fail to respond as a consequence of either intrinsic or acquired resistance. Scientific efforts are being focused toward developing new strategies to improve rituximab activity. In this report we provide an overview of recent developments in target-specific therapies and review past, ongoing, and future research tiling this diverse group of exciting novel agents.
在对靶向肿瘤性B细胞的靶向特异性药物作用机制有了更深入了解的同时，针对B细胞淋巴瘤的创新、更有效且毒性更低的治疗方案也正在出现。利妥昔单抗改变了B细胞淋巴瘤患者的治疗模式，被认为是美国食品药品监督管理局（FDA）批准的首个用于治疗淋巴增殖性疾病的有效靶向疗法。尽管其疗效和安全性良好，但接受利妥昔单抗单药治疗的患者中，仅有相对较小比例实现了持续完全缓解。为提高抗肿瘤活性，最初的策略是将利妥昔单抗与标准化疗药物联合使用，这导致了更高的缓解率，并改善了无病生存期，在某些情况下（如弥漫性大B细胞淋巴瘤）还延长了总生存期。虽然利妥昔单抗已被纳入多种化疗方案（如CVP、CHOP、FND等），但仍有相当数量的淋巴瘤患者在初始缓解后复发，或因固有或获得性耐药而无反应。目前科研工作正聚焦于开发提高利妥昔单抗活性的新策略。在本报告中，我们概述了靶向特异性疗法的最新进展，并回顾了过去、正在进行以及未来针对这类多样且令人兴奋的新型药物的研究。
