Levin Victor A, Mendelssohn Nancy D, Chan James, Stovall Mady C, Peak Scott J, Yee Jennie L, Hui Rita L, Chen David M
Department of Neurosurgery and Neuroscience, Kaiser Permanente, 1150 Veterans Boulevard, Redwood City, CA, 94063, USA,
J Neurooncol. 2015 Mar;122(1):145-50. doi: 10.1007/s11060-014-1693-x. Epub 2015 Jan 11.
Bevacizumab (BEV, Avastin(®)) produces durable objective radiological responses of 20-26 %, median response durations of 16-18 weeks, and median overall survival (mOS) of 31-40 weeks. While the use of BEV is well-established, the lack of dose-response studies in glioblastoma (GBM) patients raises the question whether current dosing practice is optimal. As a result of differing approaches to BEV dosing that ranged from the FDA approved package insert dose of 10 mg/kg every 2 weeks to 7.5 mg/kg every 3-4 weeks, among physicians within Northern California Kaiser Permanente hospitals over 4+ years, we did an IRB-approved retrospective analysis of patients seen in Northern California Kaiser Permanente facilities and treated with BEV. Between September 1, 2008 and August 31, 2013, 181 patients received BEV for tumor progression/recurrence starting 2.6 weeks after completion of chemoradiation. The integrated BEV administered dose-week (AUCBEV) for all patients had a median AUCBEV of 3.6 mg·wk/kg). Maximum likelihood analysis found patients over 65 years did worse than younger patients (p = 0.004), women lived longer (p = 0.002), and patients treated below the AUCBEV did better than those treated above the median AUCBEV (p = 0.003). mOS for BEV starting 1 month after chemoradiation was 45 versus 68 weeks (p = 0.012) and BEV starting 3 months after chemoradiation was 40 versus 74 weeks (p = 0.0085). Dosing BEV at half the standard dose for progressive/recurrent GBM was at least equivalent to or, maybe better than standard dosing. Unexplained was the observation that females had longer OS with BEV than males.
贝伐单抗（BEV，阿瓦斯汀（®））可产生持久的客观放射学反应，缓解率为20%-26%，中位缓解持续时间为16-18周，中位总生存期（mOS）为31-40周。虽然贝伐单抗的使用已得到充分确立，但胶质母细胞瘤（GBM）患者缺乏剂量反应研究，这引发了当前给药方案是否最佳的问题。在北加利福尼亚凯撒医疗集团医院的医生中，过去4年多来，贝伐单抗的给药方法各不相同，从美国食品药品监督管理局（FDA）批准的药品说明书剂量每2周10mg/kg到每3-4周7.5mg/kg不等，我们对在北加利福尼亚凯撒医疗集团设施就诊并接受贝伐单抗治疗的患者进行了一项经机构审查委员会（IRB）批准的回顾性分析。2008年9月1日至2013年8月31日，181例患者在放化疗完成后2.6周开始因肿瘤进展/复发接受贝伐单抗治疗。所有患者的贝伐单抗累积给药剂量-周（AUCBEV）中位值为3.6mg·wk/kg。最大似然分析发现，65岁以上患者的情况比年轻患者差（p = 0.004），女性生存期更长（p = 0.002），AUCBEV低于中位值的患者比高于中位值的患者情况更好（p = 0.003）。放化疗后1个月开始使用贝伐单抗的mOS为45周对68周（p = 0.012），放化疗后3个月开始使用贝伐单抗的mOS为40周对74周（p = 0.0085）。对于进展性/复发性GBM，以标准剂量的一半给予贝伐单抗至少等同于或可能优于标准给药。无法解释的是女性使用贝伐单抗的总生存期比男性长这一观察结果。
