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贝伐单抗对恶性胶质瘤患者有剂量依赖性的颅内出血风险。

Bevacizumab exerts dose-dependent risk for intracranial hemorrhage in patients with malignant gliomas.

作者信息

Lim Sanghee, Clarke Nathan H, Maloney Sara L, Sener Ugur T, Caron Samantha J, Kizilbash Sani H, Campian Jian L, Neth Bryan J, Carabenciov Ivan D, Uhm Joon, Ruff Michael W

机构信息

Division of Neuro-Oncology, Department of Neurology, Mayo Clinic, Rochester, MN, USA.

Division of Neuro-Oncology, Department of Neurology, University of Michigan, Ann Arbor, MI, USA.

出版信息

J Neurooncol. 2025 Mar;172(1):273-280. doi: 10.1007/s11060-024-04916-8. Epub 2025 Jan 2.

Abstract

PURPOSE

Bevacizumab, an anti-VEGF monoclonal antibody, has become a mainstay therapeutic in the management of malignant glioma. It is unknown if the risk of intracranial hemorrhage (ICH), a major complication associated with bevacizumab use, is dose-dependent.

METHODS

This was a single institution retrospective analysis of patients treated with bevacizumab for the management of gliomas between 2009 and 2022. Incidence rates of ICH between patients receiving low-dose (< 5 mg/kg/week) and conventional-dose (5 mg/kg/week) bevacizumab regimens were compared via competing risk analysis over time. We evaluated post-progression survival (PPS) as a secondary outcome using multivariate Cox regression.

RESULTS

One hundred and seventy-three patients were identified (low-dose group, n = 51, conventional-dose group, n = 122) for inclusion in our analysis. Cumulative incidence rates of all cases of ICH and clinically symptomatic cases of ICH were higher in the conventional-dose (17.2% for all cases, 13.7% for symptomatic) relative to the low-dose group (3.9% for all cases, 2.0% for symptomatic); p-value 0.0296 for all cases, p-value 0.0274 for symptomatic cases. On multivariate Fine-Gray regression, conventional-dose bevacizumab therapy remained significantly associated with increased risk for symptomatic ICH (SHR 8.0560; p-value 0.0442). No difference in PPS was observed between the low-dose versus conventional-dose groups.

CONCLUSIONS

Conventional-dose bevacizumab therapy (5 mg/kg/week) is associated with increased incidence of ICH in patients with malignant glioma compared to lower dose bevacizumab (< 5 mg/kg/week) in this single center retrospective cohort. No difference in PPS was observed between the low-dose versus conventional-dose groups.

摘要

目的

贝伐单抗是一种抗血管内皮生长因子(VEGF)单克隆抗体,已成为恶性胶质瘤治疗的主要手段。目前尚不清楚颅内出血(ICH)这一与使用贝伐单抗相关的主要并发症风险是否存在剂量依赖性。

方法

这是一项单机构回顾性分析,纳入了2009年至2022年间接受贝伐单抗治疗胶质瘤的患者。通过竞争风险分析比较接受低剂量(<5mg/kg/周)和常规剂量(5mg/kg/周)贝伐单抗治疗方案的患者之间ICH的发生率。我们使用多变量Cox回归评估进展后生存期(PPS)作为次要结局。

结果

共纳入173例患者(低剂量组,n = 51;常规剂量组,n = 122)进行分析。常规剂量组所有ICH病例和临床症状性ICH病例的累积发生率均高于低剂量组(所有病例为17.2%,症状性病例为13.7%),低剂量组所有病例为3.9%,症状性病例为2.0%;所有病例p值为0.0296,症状性病例p值为0.0274。在多变量Fine-Gray回归分析中,常规剂量贝伐单抗治疗仍与症状性ICH风险增加显著相关(风险比8.0560;p值0.0442)。低剂量组与常规剂量组之间未观察到PPS的差异。

结论

在这个单中心回顾性队列中,与低剂量贝伐单抗(<5mg/kg/周)相比,常规剂量贝伐单抗治疗(5mg/kg/周)与恶性胶质瘤患者ICH发生率增加相关。低剂量组与常规剂量组之间未观察到PPS的差异。

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