Szabatura Audrea H, Cirrone Frank, Harris Christy, McDonnell Anne M, Feng Yang, Voit Daniel, Neuberg Donna, Butrynski James, Fisher David C
Dana-Farber Cancer Institute, Boston, MA, USA
NewYork-Presbyterian Hospital, New York, NY, USA.
J Oncol Pharm Pract. 2015 Jun;21(3):188-93. doi: 10.1177/1078155214527143. Epub 2014 Mar 24.
Ifosfamide-induced encephalopathy is a neurotoxic adverse effect of ifosfamide chemotherapy. The objective of this study was to determine the incidence of encephalopathy in patients with lymphoma and sarcoma receiving ifosfamide chemotherapy and assess for potential risk factors that influence the incidence of encephalopathy.
A retrospective study of sarcoma and lymphoma patients receiving ifosfamide chemotherapy was performed at the participating institutions. Enrollment began 1 July 2011 and continued chronologically backwards until 100 sarcoma and 100 lymphoma patients were enrolled. Identification of ifosfamide-induced encephalopathy events was performed by reviewing provider documentation of ifosfamide infusions. Logistic regression was employed to determine associations between risk factors and ifosfamide-induced encephalopathy events.
Of the 200 patients enrolled, 29 (14.5%) patients experienced encephalopathy. Ifosfamide-induced encephalopathy occurred more frequently in the sarcoma population than the lymphoma population (24 vs. 5 patients, p < 0.001). In addition to cancer type, prior use of cisplatin, concomitant opioids, and use of CYP2B6 inhibitors remained as significant variables in the multivariate model conferring a 12.47, 2.81, and 5.17 increased odds of experiencing encephalopathy, respectively. The odds of experiencing encephalopathy were 9.0 and 1.37 times higher for a one-unit increase in serum creatinine and hemoglobin, respectively, and 0.15 times lower for a one-unit increase in albumin.
This is the first study to demonstrate that patients with sarcoma experienced ifosfamide-induced encephalopathy more often than those with lymphoma. For all patients, predisposing factors for ifosfamide-induced encephalopathy included previous cisplatin exposure, concomitant opioids and CYP2B6 inhibitors. Laboratory values that increased ifosfamide-induced encephalopathy risk included low serum albumin, increased serum creatinine, and increased hemoglobin.
异环磷酰胺所致脑病是异环磷酰胺化疗的一种神经毒性不良反应。本研究的目的是确定接受异环磷酰胺化疗的淋巴瘤和肉瘤患者中脑病的发生率，并评估影响脑病发生率的潜在危险因素。
在参与研究的机构对接受异环磷酰胺化疗的肉瘤和淋巴瘤患者进行了一项回顾性研究。入组从2011年7月1日开始，并按时间顺序逆向持续进行，直至纳入100例肉瘤患者和100例淋巴瘤患者。通过查阅异环磷酰胺输注的医疗记录来确定异环磷酰胺所致脑病事件。采用逻辑回归分析来确定危险因素与异环磷酰胺所致脑病事件之间的关联。
在纳入的200例患者中，29例（14.5%）发生了脑病。异环磷酰胺所致脑病在肉瘤患者中比淋巴瘤患者中更常见（24例对5例，p<0.001）。除癌症类型外,既往使用顺铂、同时使用阿片类药物以及使用CYP2B6抑制剂在多变量模型中仍是显著变量，分别使发生脑病的几率增加12.47、2.81和5.17倍。血清肌酐每增加一个单位，发生脑病的几率分别高9.0倍，血红蛋白升高一个单位则高1.37倍，而白蛋白每增加一个单位，发生脑病的几率低0.15倍。
这是第一项表明肉瘤患者比淋巴瘤患者更常发生异环磷酰胺所致脑病的研究。对于所有患者，异环磷酰胺所致脑病的易感因素包括既往接触顺铂、同时使用阿片类药物和CYP2B6抑制剂。增加异环磷酰胺所致脑病风险的实验室指标包括低血清白蛋白、血清肌酐升高和血红蛋白升高。
