在复发性和耐火性白血病和固体瘤中,对carfilzomib与cyclophosphamide和etoposide进行I期研究
Jessica Boklan1, Anne-Marie Langevin2, Kevin Bielamowicz3
1College of Medicine, University of Arizona, Phoenix, AZ 85004, USA.
Cancers
|September 13, 2025
概括
这一第一阶段试验评估了卡菲尔佐米布,环胺和埃托波西德在儿童白血病和固体瘤中的作用. 这种组合显示出有前途,特别是在肉瘤中,这需要进一步研究新型癌症疗法.
科学领域:
- 儿科瘤学 儿科瘤学
- 药理学 药理学 是一个学科.
- 临床试验 临床试验
背景情况:
- 新型治疗策略对于儿科,青少年和年轻成人患有复发性或耐火性白血病和固体瘤的患者至关重要.
- 临床前研究表明,carfilzomib是一种蛋白酶体抑制剂,对各种儿科恶性瘤具有活性,无论是单一治疗还是组合治疗方案.
研究的目的:
- 进行一项多中心剂量升级第一阶段研究,评估卡菲尔佐米布与环胺和埃托胺结合的安全性和耐受性.
- 确定这种组合治疗方案的最大耐受剂量 (MTD) 和推的第二期剂量 (RP2D) 在儿科患者中.
主要方法:
- 这项研究招募了6个月至30岁以下的患有复发性/耐药性白血病 (层A) 或非中枢神经系统固体瘤 (层B) 的患者.
- 每隔28天就给出一个为期5天的循环胺,埃托波西德和加大剂量的卡菲尔佐米布的治疗方案.
- 在第一周期评估剂量限制性毒性 (DLT),在第一周期 (层A) 或第二周期 (层B) 后评估反应.
主要成果:
- 招募了38名患者 (14名在A层,24名在B层).
- 甲层中卡菲尔佐米布的MTD为11mg/m2/day,观察到DLT包括血小板缩,心周炎和后倒置性脑病综合征 (PRES).
- 在B层中,RP2D被确定为周期1的20 mg/m2/days1-2和36 mg/m2/days-3-5,随后在随后的周期中为1-5天的36 mg/m2,并观察到PRES的一个DLT.
结论:
- 5天的卡菲尔佐米布/cyclophosphamide/etoposide疗法在患有固体瘤的儿科患者中被很好地容忍.
- 患有肉瘤的患者表现出最显著的益处,这表明这种组合需要对这一特定亚组进行进一步的临床评估.
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