全球精选文摘 - 转移性肾透明细胞癌患者的von Hippel-Lindau基因状态及对血管内皮生长因子靶向治疗的反应

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转移性肾透明细胞癌患者的von Hippel-Lindau基因状态及对血管内皮生长因子靶向治疗的反应

von Hippel-Lindau Gene Status and Response to Vascular Endothelial Growth Factor Targeted Therapy for Metastatic Clear Cell Renal Cell Carcinoma

Choueiri TK, Vaziri SAJ, Jaeger E 2009/7/24 12:13:21

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J Urol, 2009,

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Purpose:

The von Hippel-Lindau (VHL) gene is often inactivated (by mutation or promoter hypermethylation) in renal cell carcinoma but the relation to therapeutic outcome is unclear.

Materials and Methods:

Patients with metastatic clear cell renal cell carcinoma with available baseline tumor samples who received vascular endothelial growth factor targeted therapy were included in analysis. Patient characteristics, VHL gene status and clinical outcome were documented. Our primary end point was to test for response rate in relation to VHL inactivation. Progression-free survival and overall survival in relation to VHL status were investigated as secondary end points.

Results:

A total of 123 patients were evaluable. Response rate, median progression-free survival and median overall survival were 37% (95% CI 28–46), 10.8 (95% CI 7.7–14.8) and 29.8 (CI not estimable) months, respectively. Patients with VHL inactivation had a response rate of 41% vs 31% for those with wild-type VHL (p=0.34). Patients with loss of function mutations (frameshift, nonsense, splice and in-frame deletions/insertions) had a 52% response rate vs 31% with wild-type VHL (p=0.04). On multivariate analysis the presence of a loss of function mutation remained an independent prognostic factor associated with improved response. Progression-free survival and overall survival were not significantly different based on VHL status.

Conclusions:

To our knowledge this is the largest analysis investigating the impact of VHL inactivation on the outcome of vascular endothelial growth factor targeted agents in metastatic renal cell carcinoma. We did not find a statistically significant increase in response to vascular endothelial growth factor targeted agents in patients with VHL inactivation. Loss of function mutations identified a population of patients with a greater response. Investigation of downstream markers is under way.

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疾病资源中心

高血压	慢性阻塞性肺病
脂肪性肝病	糖尿病
卒中	肺癌
冠心病	子宫内膜异位症
结直肠癌	乳腺癌
心力衰竭	心律失常

病例分析 [栏目介绍]

甲状腺功能亢进合并黄疸

王燕燕王曙

上海交通大学附属瑞金医院内分泌科

患者，女，69岁。2009年1月无明显诱因下出现乏力，当时程度较轻，未予以重视。2009年3月患者乏力症状加重，尿色逐渐加深，大便习惯改变，颜色变淡。4月18日入我院感染科治疗，诉轻度头晕、心慌，体重减轻10kg。无肝区疼痛，无发热，无腹痛、腹泻、腹胀、里急后重，无恶性、呕吐等。入院半月前于外院就诊，查肝功能：ALT 601IU/L，AST 785IU/L，TBIL 97.7umol/L，白蛋白 41g/L，甲状腺功能：游离T3 30.6pmol/L，游离T4 51.9pmol/L，心电图示快速房颤。

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