多发性骨髓瘤的靶向治疗

 阐述抑制蛋白酶体是癌症治疗一种新方法。波替单抗（商品名：万珂）是第一个批准临床应用的蛋白酶体抑制剂。临床前试验对许多肿瘤细胞株有效。Ⅰ期临床试验确定了最佳剂量与可处理的毒性。两个Ⅱ期试验（SUMMIT与CREST）证明万珂治疗复发和／或难治的骨髓瘤患者安全而有效。Ⅲ期APEX试验比较万珂与大剂量地塞米松治疗复发的骨髓瘤证实万珂能提高有效率、缓解持续时间和总生存期。据此，研究者探索万珂与常规化疗和其他新药的联合。继续进行中的试验用万珂作为第一线药物治疗骨髓瘤结果令人鼓舞。单用万珂与其联合方案治疗血液与实体恶性肿瘤值得进一步研究。

Targeted therapy of multiple myeloma

This article reviews the proteasomes inhibition is a novel approach to cancer therapy. Bortezomib (velcade) is the first proteasomes inhibitor, it was effective in this class to be approved for clinical use. Phase I clinical trials established an optimal dosing strategy and demonstrated a manageable toxicity profile. Two phase II trial, SUMMIT and CREST demonstrated the safety and efficacy of bortezomib for patients with relapsed and/or refractory myeloma. The phase III APEX trial comparing bortezomib with high-dose dexamethasone demonstrated that bortezomib had an improved response rate, duration of remission and overall survival advantage in the setting of relapsed disease. These findings have led investigators to study bortezomib combination with conventional chemotherapy and other novel agents. Results of ongoing trial with bortezomib in the first-line treatment of myeloma have been extremely encouraging. Further studies with bortezomib as monotherapy and combination regimens in the treatment of hematologic and solid malignancies are warranted.