PDF(Pubmed)
Abstract：
Here we report the results of a single-center phase 2 clinical trial combining sorafenib tosylate, valproic acid, and sildenafil for the treatment of patients with recurrent high-grade glioma (NCT01817751). Clinical toxicities were grade 1 and grade 2, with one grade 3 toxicity for maculopapular rash (6.4%). For all evaluable patients, the median progression-free survival was 3.65 months and overall survival (OS) 10.0 months. There was promising evidence showing clinical activity and benefit. In the 33 evaluable patients, low protein levels of the chaperone GRP78 (HSPA5) was significantly associated with a better OS (p < 0.0026). A correlation between the expression of PDGFRα and OS approached significance (p < 0.0728). Five patients presently have a mean OS of 73.6 months and remain alive. This is the first therapeutic intervention glioblastoma trial to significantly associate GRP78 expression to OS. Our data suggest that the combination of sorafenib tosylate, valproic acid, and sildenafil requires additional clinical development in the recurrent glioma population.
摘要：
在这里，我们报告了联合对甲苯磺酸盐索拉非尼的单中心2期临床试验的结果，丙戊酸,和西地那非治疗复发性高级别胶质瘤患者（NCT01817751）。临床毒性为1级和2级，黄斑丘疹的毒性为3级（6.4％）。对于所有可评估的患者，中位无进展生存期为3.65个月,总生存期(OS)为10.0个月.有有希望的证据显示临床活动和益处。在33个可评估的患者中，低蛋白质水平的伴侣GRP78（HSPA5）与更好的OS显著相关（p<0.0026）。PDGFRα的表达与OS之间的相关性接近显著性(p<0.0728)。目前有五名患者的平均OS为73.6个月，并且仍然存活。这是第一个将GRP78表达与OS显着相关的治疗性干预胶质母细胞瘤试验。我们的数据表明，对甲苯磺酸盐索拉非尼的组合，丙戊酸,在复发的神经胶质瘤人群中，西地那非需要额外的临床开发。
