Catley Laurence, Tai Yu-Tzu, Chauhan Dharminder, Anderson Kenneth C
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Mayer 551, 44 Binney Street, Boston, MA 02115, USA.
Drug Resist Updat. 2005 Aug;8(4):205-18. doi: 10.1016/j.drup.2005.06.001. Epub 2005 Jul 12.
The introduction of melphalan and prednisone 40 years ago was a significant advance in the treatment of multiple myeloma (MM). In the following decades, significant advances were few, but included landmarks, such as the introduction of VAD and autologous transplantation during the 1980s and bisphosphonates in the 1990s. Although response rates to therapy were increased, overall survival was not significantly improved. In 1999, the treatment of myeloma was revolutionized by the introduction of thalidomide. Subsequently, the development of the immunomodulatory thalidomide analogues and the proteasome inhibitor bortezomib have impacted on response rates to therapy in relapsed and refractory myeloma and are currently being evaluated as primary therapy for myeloma. Early results suggest activity in combination with standard therapy to overcome drug resistance in patients with early stage disease and are changing treatment strategies in multiple myeloma. As an increasing number of other novel therapeutics is identified and mechanisms of resistance are elucidated, combinations of these drugs will be developed to optimize new therapeutic regimens.
40年前美法仑和泼尼松的引入是多发性骨髓瘤（MM）治疗的一项重大进展。在接下来的几十年里，重大进展寥寥无几，但包括一些里程碑事件，比如20世纪80年代引入VAD和自体移植，以及90年代引入双膦酸盐。尽管治疗的缓解率有所提高，但总生存期并未得到显著改善。1999年，沙利度胺的引入彻底改变了骨髓瘤的治疗。随后，免疫调节性沙利度胺类似物和蛋白酶体抑制剂硼替佐米的研发对复发和难治性骨髓瘤的治疗缓解率产生了影响，目前正在作为骨髓瘤的一线治疗进行评估。早期结果表明，其与标准疗法联合使用可克服早期疾病患者的耐药性，正在改变多发性骨髓瘤的治疗策略。随着越来越多的其他新型疗法被发现，耐药机制得以阐明，这些药物的联合应用将被开发出来以优化新的治疗方案。
