Milano Amalia, Apice Gaetano, Ferrari Ettore, Fazioli Flavio, de Rosa Vincenzo, de Luna Antonella Salzano, Iaffaioli Rosario Vincenzo, Caponigro Francesco
Istituto Nazionale Tumori, Fondazione G. Pascale, Via M. Semmola, 80131 Napoli, Italy.
Crit Rev Oncol Hematol. 2006 Jul;59(1):74-84. doi: 10.1016/j.critrevonc.2005.12.002. Epub 2006 Mar 13.
Doxorubicin and ifosfamide are the two most active drugs in the treatment of patients with advanced, soft tissue sarcoma (STS) of most histologic subtypes, aside from gastrointestinal stromal tumor (GIST). However, after failure of these drugs, alone or in combination, patients with advanced STS have few therapeutic options and the search for new active drugs is well worth pursuing. ET-743, a DNA minor groove binder, which blocks cell cycle progression in G2/M phase through a p53-independent apoptotic process, represents the most promising among novel compounds in STS, since recently completed phase II trials have consistently shown high survival, in spite of the relatively low incidence of major objective responses. The potential for combination with other active compounds further increases the appeal of ET-743. Imatinib mesylate is being tested also in STS other than GIST, which can overexpress one or more of the tyrosine kinases inhibited by imatinib; however, negative data have recently been presented. Clinical studies with a number of other compounds are ongoing or planned. However, investigators involved in the management of patients with advanced STS are to be increasingly aware of the emergence of new molecular targets and genetic profiles in different histologic subtypes, according to which treatment strategies should be adapted.
除胃肠道间质瘤（GIST）外，多柔比星和异环磷酰胺是治疗大多数组织学亚型的晚期软组织肉瘤（STS）患者最有效的两种药物。然而，在这些药物单独或联合使用失败后，晚期STS患者的治疗选择很少，因此寻找新的活性药物非常值得。ET-743是一种DNA小沟结合剂，通过非p53依赖的凋亡过程阻断G2/M期的细胞周期进程，是STS新型化合物中最有前景的一种，因为最近完成的II期试验一直显示出高生存率，尽管主要客观缓解率相对较低。与其他活性化合物联合使用的潜力进一步增加了ET-743的吸引力。甲磺酸伊马替尼也正在非GIST的STS中进行测试，这些STS可能会过度表达一种或多种被伊马替尼抑制的酪氨酸激酶；然而，最近公布的数据是阴性的。目前正在进行或计划进行许多其他化合物的临床研究。然而，参与晚期STS患者管理的研究人员应越来越意识到不同组织学亚型中新分子靶点和基因谱的出现，并据此调整治疗策略。
