ACT-18 SHOULD THE DOSE OF TEMOZOLOMIDE BE DECREASED FOR PATIENTS WITH HIGH-GRADE GLIOMAS WHO ARE ON HEMODIALYSIS?
ACT-18 SHOULD THE DOSE OF TEMOZOLOMIDE BE DECREASED FOR PATIENTS WITH HIGH-GRADE GLIOMAS WHO ARE ON HEMODIALYSIS?
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DOI：
10.1093/noajnl/vdz039.066
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发表时间：
2019-12-16
期刊：
影响因子：
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通讯作者：
Sasaki H
中科院分区：
文献类型：
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作者：
Muto J;Matsutani T;Matsuda R;Kinoshita M;Oikawa M;Johan P;Adachi K;Hirose Y;Sasaki H
尚未研究重度肾损害患者（肌酐清除率低于36 mL/min/m2）或血液透析患者中替莫唑胺的药代动力学。替莫唑胺及其代谢产物主要经尿液排泄，因为这些物质在体内的滞留可能导致患有高级别胶质瘤的血液透析患者的不良事件增加。来自七个机构的八名患有高级别胶质瘤的血液透析患者被纳入本研究。评价患者特征、治疗方案、临床病程、病理/分子学结果和不良事件。组织病理学诊断为异柠檬酸脱氢酶（IDH）野生型胶质母细胞瘤4例，其他未特指（NOS）胶质母细胞瘤2例，IDH突变型间变性星形细胞瘤1例。7例患者中的5例完成了伴随替莫唑胺（75 mg/m2）的放疗（48-60戈伊），随后每28天辅助5天替莫唑胺（150 mg/m2）。在替莫唑胺的整个治疗过程中，57%（41.7-61%：非血液透析患者数据，下同）的患者发生重度（不良事件通用术语标准（CTCAE）3级以上）淋巴细胞减少症，0%（1-15.4%）的患者发生中性粒细胞减少症，14%（0-16.7%）的患者发生血小板减少症。一般来说，骨髓抑制的频率和程度不会增加血液透析患者的高级别胶质瘤。7例患者中有2例（28.5%）死于感染性疾病，尽管与骨髓抑制无直接相关性，这与日本血液透析患者感染导致的死亡率21.9%相似。接受血液透析研究的高级别胶质瘤患者在伴随放化疗和维持治疗期间不需要降低替莫唑胺剂量。然而，需要仔细的临床和血液学观察，以避免严重的血液毒性和感染。
The pharmacokinetics of temozolomide in patients with severe renal impairments (creatinine clearance less than 36 mL/min/m2) or in hemodialysis patients has not been investigated. Temozolomide and its metabolic products are mainly excreted in urine, as retention of these in the body may result in increased adverse events in hemodialysis patients harboring a high-grade glioma. Eight hemodialysis patients with high-grade gliomas from seven institutions were included in the study. Patient characteristics, treatment schedule, clinical course, pathological/molecular findings, and adverse events were evaluated. The histopathological diagnoses were Isocitrate dehydrogenase (IDH) wild-type glioblastoma in four cases, Not other specified (NOS) glioblastoma in two cases and IDH-mutant anaplastic astrocytoma in one case. Five of the seven patients completed radiotherapy (48–60 Gy) with concomitant temozolomide (75 mg/m2) followed by adjuvant 5-day temozolomide (150 mg/m2) every 28 days. During the entire course of treatment with temozolomide, severe (Common Terminology Criteria for Adverse Events (CTCAE) more than grade 3) lymphocytopenia occurred in 57%(41.7–61%: non hemodialysis patients data, the same as below), neutropenia in 0%(1–15.4%) and thrombocytopenia in 14%(0–16.7%) of the patients. Generally, the frequency and degree of myelosuppression do not increase in hemodialysis patients with high-grade gliomas. Two of the seven (28.5%) patients died of infectious disease despite having no direct correlation to myelosuppression that is similar rate of 21.9% of the death results from infection in hemodialysis patients in Japan. The high-grade glioma patients under study on hemodialysis did not require decreasing doses of Temozolomide during concomitant radiochemotherapy and maintenance therapy. However, careful clinical and hematological observation is required to avoid critical hematotoxicity and infection.