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替莫唑胺同步放化疗用于接受血液透析的高级别胶质瘤患者:7例病例系列

Temozolomide radiochemotherapy for high-grade glioma patients with hemodialysis: a case series of 7 patients.

作者信息

Muto Jun, Matsutani Tomoo, Matsuda Ryosuke, Kinoshita Masashi, Oikawa Mitsuteru, Pallud Johan, Sasaki Hikaru

机构信息

Department of Neurosurgery, Fujita Health University, Japan.

Department of Neurosurgery, Keio University School of Medicine, Japan.

出版信息

Neurooncol Pract. 2020 Jan;7(1):111-117. doi: 10.1093/nop/npz034. Epub 2019 Dec 3.

Abstract

BACKGROUND

The pharmacokinetics of temozolomide (TMZ) in patients with severe renal impairments (creatinine clearance, <36 mL/min/m) or in hemodialysis (HD) patients has not been investigated. TMZ and its metabolic products are mainly excreted in urine, as retention of these in the body may result in increased adverse events in HD patients.

METHODS

Seven HD patients with high-grade gliomas from 6 institutions were included in the study. Patient characteristics, treatment schedule, clinical course, pathological/molecular findings, and adverse events were evaluated.

RESULTS

The histopathological diagnoses were isocitrate dehydrogenase () wild-type glioblastoma in 4 cases, not other specified (NOS) glioblastoma in 2 cases, and -mutant anaplastic astrocytoma in 1 case. Five of the 7 patients completed radiotherapy (48-60 Gy) with concomitant TMZ (75 mg/m) followed by adjuvant 5-day TMZ (150 mg/m) every 28 days. During the entire course of treatment with TMZ, severe (Common Terminology Criteria for Adverse Events [CTCAE] ≥ Grade 3) lymphocytopenia occurred in 57%, neutropenia in 0%, and thrombocytopenia in 14% of the patients. Generally, the frequency and degree of myelosuppression do not increase in HD patients with high-grade gliomas. Two of the 7 (28.5%) patients died of infectious disease despite having no direct correlation to myelosuppression; that is similar to the death rate of 21.9% resulting from infection in HD patients in Japan.

CONCLUSIONS

Decreasing the dose of TMZ might not be required in HD patients with high-grade gliomas during concomitant radiochemotherapy and maintenance therapy. However, careful clinical and hematological observation is required to avoid critical hematotoxicity and infection.

摘要

背景

尚未对严重肾功能损害(肌酐清除率<36 mL/min/m²)患者或血液透析(HD)患者中替莫唑胺(TMZ)的药代动力学进行研究。TMZ及其代谢产物主要经尿液排泄,因为这些物质在体内潴留可能导致HD患者不良事件增加。

方法

本研究纳入了来自6家机构的7例患有高级别胶质瘤的HD患者。对患者的特征、治疗方案、临床病程、病理/分子学结果及不良事件进行了评估。

结果

组织病理学诊断为4例异柠檬酸脱氢酶(IDH)野生型胶质母细胞瘤、2例未另行指定(NOS)的胶质母细胞瘤和1例IDH突变型间变性星形细胞瘤。7例患者中有5例完成了放疗(48 - 60 Gy),同时给予TMZ(75 mg/m²),随后每28天进行5天的辅助TMZ治疗(150 mg/m²)。在TMZ治疗的整个过程中,57%的患者出现严重(不良事件通用术语标准[CTCAE]≥3级)淋巴细胞减少,0%的患者出现中性粒细胞减少,14%的患者出现血小板减少。一般来说,高级别胶质瘤HD患者的骨髓抑制频率和程度并未增加。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关联;这与日本HD患者因感染导致的21.9%的死亡率相似。

结论

在高级别胶质瘤HD患者同步放化疗及维持治疗期间,可能无需降低TMZ剂量。然而,需要进行仔细的临床和血液学观察,以避免严重的血液毒性和感染。

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