Current status of bortezomib in the treatment of multiple myeloma.
Current status of bortezomib in the treatment of multiple myeloma.
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DOI：
10.1007/s11899-007-0018-y
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发表时间：
2007-05-01
影响因子：
2.9
通讯作者：
Cavo, Michele
中科院分区：
文献类型：
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作者：
Cavo, Michele
硼替佐米（以前的PS-341）是第一个进入癌症患者临床试验的蛋白酶体抑制剂。临床前研究表明，这种新型药物直接抑制骨髓瘤细胞的增殖，诱导其凋亡，并通过改变骨髓瘤和基质细胞的相互作用和通过核因子κ B依赖性细胞因子分泌消除旁分泌肿瘤生长，促使设计了硼替佐米在晚期复发性和/或难治性多发性骨髓瘤患者中的大型II期和III期研究。这些研究的有利结果导致了硼替佐米在至少第二次治疗后进展的多发性骨髓瘤患者中的加速批准，最近，扩大了对既往治疗失败的患者的二线使用的批准。硼替佐米与各种药物的联合研究，包括地塞米松，DNA损伤药物（如美法仑，环磷酰胺和多柔比星），沙利度胺和来那度胺，目前正在复发/难治性和新诊断疾病的患者中进行。硼替佐米可能是开发更有效的治疗策略以改善多发性骨髓瘤患者结局的“支柱”。
Bortezomib (formerly PS-341) has been the first proteasome inhibitor to enter clinical trials in cancer patients. Preclinical studies showing that this novel agent directly inhibits the proliferation of myeloma cells, induces their apoptosis, and abrogates paracrine tumor growth through alteration of interactions of myeloma and stromal cells and through nuclear factor kappaB-dependent cytokine secretion prompted the design of large phase II and III studies of bortezomib in patients with advanced relapsed and/or refractory multiple myeloma. Favorable results of these studies led to accelerated approval for use of bortezomib in patients with multiple myeloma who have progressed after at least their second therapy and, more recently, to expanded approval for second-line use in patients in whom one prior therapy has failed. Combination studies of bortezomib with various agents, including dexamethasone, DNA-damaging drugs (such as melphalan, cyclophosphamide, and doxorubicin), thalidomide, and lenalidomide, are currently ongoing in patients with both relapsed/refractory and newly diagnosed disease. Bortezomib may be the "backbone" for the development of more effective treatment strategies to improve patient outcome in multiple myeloma.