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奥拉帕利联合替莫唑胺治疗脑胶质瘤:回顾性病例系列。

Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series.

机构信息

From the Memorial Sloan Kettering Cancer Center, New York City, NY.

出版信息

Neurology. 2022 Oct 24;99(17):750-755. doi: 10.1212/WNL.0000000000201203.

Abstract

BACKGROUND AND OBJECTIVES

To report the tolerability and efficacy of olaparib with temozolomide (TMZ) for glioma.

METHODS

Single-center retrospective series of patients with glioma treated with olaparib/TMZ from September 2018 to December 2021.

RESULTS

Twenty patients (median age: 42 years, median Karnofsky Performance Status: 90) received olaparib/TMZ for diagnoses of -mutant oligodendroglioma (n = 5), mutant astrocytoma grade 2-3 (n = 4), -mutant astrocytoma grade 4 (n = 7), or wildtype glioma (n = 4). One patient was treated upfront and 19 at recurrence (median = 3). Olaparib 150 mg was administered 3 times/week concurrent with TMZ 50-75 mg/m daily. Fatigue, gastrointestinal symptoms, and hematologic toxicity were common. Six of 20 patients required dose reduction (n = 4) or discontinuation (n = 2) due to toxicity. Radiographic response was evaluable in 16 and observed (complete + partial) in 4/8 with -mutant grade 2-3 glioma. No responses were seen in patients with grade 4 -mutant astrocytomas (0/5) or -wildtype gliomas (0/3). Progression-free survival was 7.8, 1.3, and 2.0 months, respectively.

DISCUSSION

Olaparib/TMZ resulted in objective radiographic response in 50% of evaluable patients with recurrent -mutant grade 2-3 gliomas with encouraging progression-free survival and manageable toxicity. This supports a prospective trial of olaparib/TMZ for this population.

CLASSIFICATION OF EVIDENCE

This case series provides Class IV evidence that treatment with olaparib/TMZ may result in radiographic response in patients with glioma.

摘要

背景与目的

报告奥拉帕利联合替莫唑胺(TMZ)治疗胶质瘤的耐受性和疗效。

方法

对 2018 年 9 月至 2021 年 12 月在单中心接受奥拉帕利/TMZ 治疗的胶质瘤患者进行回顾性系列研究。

结果

20 例患者(中位年龄:42 岁,中位卡氏功能状态评分:90)接受奥拉帕利/TMZ 治疗,诊断为 -突变型少突胶质细胞瘤(n=5)、突变型 2-3 级星形细胞瘤(n=4)、-突变型 4 级星形细胞瘤(n=7)或野生型胶质瘤(n=4)。1 例患者为初始治疗,19 例为复发(中位=3)。奥拉帕利 150 mg,每周 3 次,同时给予 TMZ 50-75 mg/m2 每日 1 次。疲劳、胃肠道症状和血液学毒性很常见。由于毒性,20 例患者中有 6 例(n=4)需要减少剂量或停药(n=2)。在 16 例可评估的患者中,有 4 例(8 例中有 4 例)观察到影像学反应,-突变型 2-3 级胶质瘤。4 例 4 级 -突变型星形细胞瘤(n=5)或 3 例 -野生型胶质瘤(n=3)未见反应。无进展生存期分别为 7.8、1.3 和 2.0 个月。

讨论

奥拉帕利/TMZ 治疗复发性 -突变型 2-3 级胶质瘤患者的客观影像学反应率为 50%,无进展生存期令人鼓舞,毒性可管理。这支持对这一人群进行奥拉帕利/TMZ 的前瞻性试验。

证据分类

这项病例系列研究提供了 IV 级证据,表明奥拉帕利/TMZ 治疗可能导致胶质瘤患者的影像学反应。

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