Caravita Tommaso, de Fabritiis Paolo, Palumbo Antonio, Amadori Sergio, Boccadoro Mario
Myeloma Unit, Hematology Department, St Eugenio Hospital, Rome, Italy.
Nat Clin Pract Oncol. 2006 Jul;3(7):374-87. doi: 10.1038/ncponc0555.
Proteasome inhibition represents a new anticancer approach, with the potential effect of arresting tumor growth, metastasis and angiogenesis through the activation of multiple mechanisms. Bortezomib is a biologically active agent, producing predictable, dose-related and reversible proteasome inhibition; it has shown antitumor activity in various malignancies and is the first proteasome inhibitor to be used in clinical practice. Several trials demonstrated that bortezomib is relatively well tolerated, causing manageable nonhematologic and hematologic toxicity. The drug was approved in 2003 by the FDA for the treatment of patients with multiple myeloma who had received at least two prior therapies and demonstrated disease progression on the last therapy; its application was expanded recently for second-line treatment. This article summarizes the principal clinical trials of bortezomib and discusses its efficacy in solid and hematologic tumors.
蛋白酶体抑制代表了一种新的抗癌方法,它具有通过激活多种机制来阻止肿瘤生长、转移和血管生成的潜在作用。硼替佐米是一种生物活性剂,可产生可预测的、剂量相关的和可逆的蛋白酶体抑制作用;它在多种恶性肿瘤中均显示出抗肿瘤活性,并且是首个用于临床实践的蛋白酶体抑制剂。多项试验表明,硼替佐米的耐受性相对良好,会引起可控的非血液学和血液学毒性。该药物于2003年被美国食品药品监督管理局(FDA)批准用于治疗接受过至少两种先前治疗且在最后一次治疗中出现疾病进展的多发性骨髓瘤患者;其应用最近已扩展至二线治疗。本文总结了硼替佐米的主要临床试验,并讨论了其在实体瘤和血液系统肿瘤中的疗效。