Haemato-oncology Unit, Royal Marsden Hospital Downs Road, Sutton, Surrey, UK.
Ther Clin Risk Manag. 2006 Sep;2(3):271-9. doi: 10.2147/tcrm.2006.2.3.271.
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 (NFkappaB). 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.
硼替佐米的问世是多发性骨髓瘤治疗领域的重大突破。硼替佐米是一种新型蛋白酶体抑制剂，目前被批准用于治疗移植后复发或不适合移植的患者的二线治疗多发性骨髓瘤。在临床前研究中，硼替佐米表现出多种不同的抗骨髓瘤作用，包括细胞周期紊乱和细胞凋亡诱导、骨髓微环境改变和核因子 kappa B（NFkappaB）抑制。由于其新颖的作用机制，硼替佐米已被证明可诱导先前耐药患者（包括具有不良细胞遗传学风险的患者）产生反应，并与单独使用地塞米松相比，增加了复发患者的无进展生存期和总生存期。硼替佐米耐受性良好，可在门诊环境下使用，毒性可控制。周围神经病是最常见的剂量限制毒性，血小板减少症通常可以通过血小板输注来管理，而不会减少或停止用药。硼替佐米与地塞米松联合使用具有协同作用，还能使骨髓瘤细胞对其他化疗药物的作用敏感，在复发患者中，其反应率超过 50%。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使用时，反应率为 80%-90%，重要的是，外周血造血干细胞动员能力不受影响。
