Bortezomib (Velcadetrade mark) in the Treatment of Multiple Myeloma.
Bortezomib (Velcadetrade mark) in the Treatment of Multiple Myeloma.
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DOI：
10.2147/tcrm.2006.2.3.271
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发表时间：
2006-09
影响因子：
2.8
通讯作者：
Davies FE
中科院分区：
文献类型：
--
作者：
Field-Smith A;Morgan GJ;Davies FE
硼替佐米是一种新型的蛋白酶体抑制剂，它的引入是多发性骨髓瘤治疗的一个重大突破。目前已批准用于治疗移植后复发性骨髓瘤或作为不适合移植患者的二线治疗。在临床前研究中，硼替佐米显示了许多不同的抗骨髓瘤作用，包括破坏细胞周期和诱导细胞凋亡、改变骨髓微环境和抑制核因子κ B（NFκB）。由于其新的作用机制，硼替佐米已被证明可诱导先前难治性患者（包括具有不良风险细胞遗传学的患者）的应答，并且与地塞米松单独治疗相比，可增加复发患者的无进展生存期和总生存期。它的耐受性良好，可以在门诊环境中给药，毒性可控。周围神经病变是最常见的剂量限制性毒性，血小板减少症通常可以通过血小板输注进行管理，而无需减少或省略剂量。硼替佐米与地塞米松组合显示出协同效应，并且还使骨髓瘤细胞对其他化疗剂的作用敏感，在复发情况下显示出超过50%的主要应答率。正在进行的一线治疗试验的初步数据令人鼓舞，当硼替佐米与其他药物联合给药时，缓解率为80%-90%，重要的是，动员外周血干细胞的能力没有受损。
The introduction of bortezomib, a novel first-in-class proteasome inhibitor, has been a major break through in the treatment of multiple myeloma. It is currently approved for the treatment of myeloma in the relapsed setting post transplant or as a second line treatment in patients unsuitable for transplantation. In pre-clinical studies bortezomib showed a number of different anti-myeloma effects including disruption of the cell cycle and induction of apoptosis, alteration of the bone marrow microenvironment and inhibition of nuclear factor kappa B (NFκB). Due to its novel mechanism of action, bortezomib has been shown to induce responses in previously refractory patients (including those with poor risk cytogenetics), and results in an increased progression free and overall survival in relapsed patients when compared with dexamethasone treatment alone. It is well tolerated and can be administered in the outpatient setting with manageable toxicities. Peripheral neuropathy is the most common dose limiting toxicity and thrombocytopenia can generally be managed with platelet transfusions without reducing or omitting doses. Bortezomib shows a synergistic effect in combination with dexamethasone and also sensitises myeloma cells to the effects of other chemotherapeutic agents with major response rates of over 50% being shown in the relapsed setting. Initial data from ongoing trials in front line therapy are encouraging with response rates of 80%–90% when bortezomib is given in combination with other agents and importantly, the ability to mobilize peripheral blood stem cells is not impaired.