Jain Salvia, Diefenbach Catherine, Zain Jasmine, O'Connor Owen A
NYU Cancer Institute, Division of Hematology and Medical Oncology, NYU Langone Medical Center, New York, NY, USA.
Core Evid. 2011;6:43-57. doi: 10.2147/CE.S13838. Epub 2011 Apr 4.
Proteasome inhibition forms the cornerstone of antimyeloma therapy. The first-in-class proteasome inhibitor, bortezomib, either alone or in combination with other chemotherapeutic agents, induces high overall response rates and response qualities in patients with clinically and molecularly defined high-risk disease. However, resistance to bortezomib and neurotoxicity associated with the treatment remain challenging issues. Carfilzomib is a novel, well tolerated, irreversible proteasome inhibitor with minimal neurotoxicity. Carfilzomib demonstrates promising activity in myeloma patients who are refractory to bortezomib and immunomodulatory agents. This review focuses on the pharmacology, safety, and efficacy of carfilzomib for the treatment of multiple myeloma in bortezomib-naïve and bortezomib-exposed populations.
蛋白酶体抑制是抗骨髓瘤治疗的基石。首个蛋白酶体抑制剂硼替佐米，无论是单独使用还是与其他化疗药物联合使用，在临床和分子层面定义的高危疾病患者中均能诱导出较高的总体缓解率和缓解质量。然而，对硼替佐米的耐药性以及与治疗相关的神经毒性仍然是具有挑战性的问题。卡非佐米是一种新型、耐受性良好、不可逆的蛋白酶体抑制剂，神经毒性极小。卡非佐米在对硼替佐米和免疫调节剂难治的骨髓瘤患者中显示出有前景的活性。本综述重点关注卡非佐米在未接触过硼替佐米和接触过硼替佐米的人群中治疗多发性骨髓瘤的药理学、安全性和疗效。
