Adis, Auckland, New Zealand.
Drugs. 2012 Oct 22;72(15):2023-32. doi: 10.2165/11209010-000000000-00000.
Intravenous carfilzomib is a peptide epoxyketone, next-generation proteasome inhibitor, which has been granted accelerated approval in the US for the treatment of patients with multiple myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent (thalidomide or lenalidomide), and have demonstrated disease progression on or within 60 days of completion of the last therapy. Carfilzomib displays high selectivity for and irreversibly inhibits the chymotrypsin-like catalytic activity of the 20S proteasome core particle, which results in cell growth arrest and apoptosis. In the pivotal, phase II, noncomparative trial in heavily pre-treated patients (n = 266) with relapsed and refractory multiple myeloma, intravenous carfilzomib administered in 28-day cycles for up to 12 cycles produced an overall response rate of 23.7% in the response-evaluable population. The median duration of response was 7.8 months, the median progression-free survival was 3.7 months and the median overall survival was 15.6 months. Carfilzomib had an acceptable tolerability profile in patients with relapsed, or relapsed and refractory, multiple myeloma. There was a low incidence of grade 3 or higher peripheral neuropathy.
静脉注射卡非佐米是一种肽环氧酮类、下一代蛋白酶体抑制剂，已在美国获得加速批准，用于治疗至少接受过两种先前治疗的多发性骨髓瘤患者，包括硼替佐米和免疫调节剂（沙利度胺或来那度胺），并且在最后一次治疗完成后 60 天内或之内显示疾病进展。卡非佐米对 20S 蛋白酶体核心颗粒的糜蛋白酶样催化活性具有高选择性和不可逆抑制作用，导致细胞生长停滞和凋亡。在先前接受大量治疗的复发和难治性多发性骨髓瘤患者（n=266）的关键性、Ⅱ期非比较试验中，在 28 天的周期中最多接受 12 个周期的静脉注射卡非佐米，在可评估反应的人群中产生了 23.7%的总体缓解率。反应持续时间的中位数为 7.8 个月，无进展生存期的中位数为 3.7 个月，总生存期的中位数为 15.6 个月。卡非佐米在复发或复发和难治性多发性骨髓瘤患者中的耐受性良好。外周神经病变 3 级或更高级别的发生率较低。
