NYC Health and Hospitals/Queens, Jamaica, NY, USA.
Vanderbilt University Medical Center, Nashville, TN, USA.
J Oncol Pharm Pract. 2021 Dec;27(8):1891-1895. doi: 10.1177/1078155220971794. Epub 2020 Nov 8.
The incidence of Ifosfamide-induced encephalopathy (IIE) ranges from 5-30%. Aprepitant and fosaprepitant may increase the risk of IIE; however, data is limited. The objective of this study was to characterize the incidence of IIE in patients receiving concomitant fosaprepitant.
This single-center, retrospective chart review included adult patients diagnosed with sarcoma who received at least one administration of high dose ifosfamide (≥1800mg/m) and fosaprepitant between January 2017 and June 2018. The primary endpoint was the percentage of patient cycles in which IIE was experienced. Secondary endpoints included characterization of IIE management strategies, time to IIE resolution, and the incidence of IIE upon ifosfamide re-challenge. Subgroup analyses were performed to assess whether the following variables predisposed a patient to neurotoxicity: elevated serum creatinine, hypoalbuminemia, metabolic acidosis, hyperbilirubinemia, shorter infusion time, and higher body mass index. The role of CYP2B6 inhibitors and prior cisplatin use were also examined.
Fifty-one patients who received 215 total cycles of ifosfamide were included. Twenty (9.3%) patient cycles included documented evidence of IIE. The most common management strategies were to prolong the infusion time and administer methylene blue. The mean time to resolution of IIE was 2.58 days. The incidence of secondary IIE upon re-challenge was 26.3%. Baseline albumin <3.5 g/dL (p<0.001) was statistically associated with the development of IIE.
Co-administration of fosaprepitant and ifosfamide in sarcoma appears to be safe. Hypoalbuminemia was a notable risk factor confirmed in this study. Further research is needed to delineate IIE risk factors.
异环磷酰胺脑病（IIE）的发病率为 5-30%。阿瑞匹坦和福沙匹坦可能会增加 IIE 的风险；然而，数据有限。本研究的目的是描述接受福沙匹坦联合治疗的患者中 IIE 的发生率。
这是一项单中心、回顾性病历审查，纳入了 2017 年 1 月至 2018 年 6 月期间接受至少一次高剂量异环磷酰胺（≥1800mg/m）和福沙匹坦治疗的肉瘤成年患者。主要终点是发生 IIE 的患者周期百分比。次要终点包括 IIE 管理策略的特征、IIE 缓解时间以及重新使用异环磷酰胺时 IIE 的发生率。进行了亚组分析，以评估以下变量是否使患者易发生神经毒性：血清肌酐升高、低白蛋白血症、代谢性酸中毒、高胆红素血症、输注时间较短和体重指数较高。还检查了 CYP2B6 抑制剂和先前顺铂使用的作用。
共纳入 51 例接受 215 个异环磷酰胺周期的患者。20 个（9.3%）患者周期有 IIE 的明确证据。最常见的管理策略是延长输注时间和使用亚甲蓝。IIE 缓解的平均时间为 2.58 天。重新使用异环磷酰胺时 IIE 的发生率为 26.3%。基线白蛋白<3.5g/dL（p<0.001）与 IIE 的发生具有统计学相关性。
在肉瘤中联合使用福沙匹坦和异环磷酰胺似乎是安全的。低白蛋白血症是本研究中确认的一个显著危险因素。需要进一步研究来阐明 IIE 的危险因素。
