沙利度胺在恶性肿瘤治疗中的应用

Thalidomide in cancer treatment

沙利度胺最初作为镇静药应用,因致畸性而被撤出市场。后发现它具有抑制TNFα的作用,1998年被美国FDA批准用于治疗麻风病结节性红斑。20世纪90年代随着对血管生成对肿瘤增殖、生长重要性的日益认识,其抗血管生成活性也逐渐被发现,并在多种肿瘤的治疗中进行了研究。现认为沙利度胺是一免疫调节和抗血管生成药物,但是其具体的作用机制还不明确。目前,沙利度胺已经成为复发和难治多发性骨髓瘤标准治疗的一部分,对骨髓纤维化、骨髓增生异常综合征的治疗值得期待,和其他药物联用对卡波西肉瘤、黑色素瘤、肾癌、前列腺癌等的治疗有一定效果。沙利度胺类似物,如CC5013,毒性减少且活性增强,现正在进行多种肿瘤治疗的ⅠⅡⅢ期临床试验。

Thalidomide,initially introduced as a sedative,was withdrawn from the market in the early 1960s because of it's teratogenicity.In1998,it was proved by FDA to be used in the treatment of erythema nodosum leprosum.It's antiangiogenic properties were recognized in the 1990s when the importance of angiogenisis became increasing apparent as a critical step in the proliferation and spread of malignant neoplasms.Since then,it has been used in a variety of diseases.Thalidomide has already become part of standard therapy for the treatment of patients with relapsed and refractory multiple myeloma.It has shown promising activity in MMM and MDS.Combination of thalidomide and other effective drug in solid tumor have demonstrated useful activity,especially in Kaposi's sarcoma,malignant melanoma,renal cell carcinoma and prostate cancer.Thalidomide analogs has improved antitumor activity without the teratogenic side effects.One such analog,CC-5013 has shown promise in myeloma and is being tested in several clinical trials.