Rini Brian I, Jaeger Erich, Weinberg Vivian, Sein Nancy, Chew Karen, Fong Kristen, Simko Jeffery, Small Eric J, Waldman Frederic M
Department of Medicine, the University of California San Francisco, San Francisco, California, USA.
BJU Int. 2006 Oct;98(4):756-62. doi: 10.1111/j.1464-410X.2006.06376.x. Epub 2006 Jul 7.
To describe the relationship among patient characteristics, Von Hippel-Lindau (VHL) gene status and clinical outcome in metastatic renal cell carcinoma (RCC) in patients receiving vascular endothelial growth factor (VEGF)-targeted therapy.
All patients with metastatic RCC who received therapy with interferon-alpha plus bevacizumab, SU11248 or AG013736 at the authors' institution were considered. Clinical features were collected and activation status of the VHL gene (VHL) was determined from baseline paraffin-embedded tumour samples. Tumour response, time to tumour progression (TTP) and overall survival were recorded.
Forty-three patients were evaluable for determination of VHL status and clinical response. There was an objective response in 18 patients (43%; 95% confidence interval 28-59%). The median TTP for the entire cohort was 8.1 months. There was an improved clinical outcome in patients with the following clinical features: male gender, lack of hepatic metastases, no previous radiation therapy and higher baseline haemoglobin level. Twenty-six patients (60%) had evidence of VHL mutation or promoter methylation; such patients had an objective response rate of 48%, vs 35% in patients with no VHL mutation or methylation. Patients with VHL methylation or a mutation predicted to truncate or shift the VHL reading frame had a median TTP of 13.3 months, vs 7.4 months in patients with none of these features (P = 0.06).
VEGF-targeted therapy is active in metastatic RCC and the response can be associated with certain clinical features. The TTP with VEGF-targeted therapy might be prolonged in patients with VHL methylation or mutations that truncate or shift the VHL reading frame. Further investigation of VHL pathway components is needed to understand the biology of the response to VEGF-targeted agents in metastatic RCC.
描述接受血管内皮生长因子（VEGF）靶向治疗的转移性肾细胞癌（RCC）患者的特征、冯·希佩尔-林道（VHL）基因状态与临床结局之间的关系。
纳入在作者所在机构接受α-干扰素联合贝伐单抗、SU11248或AG013736治疗的所有转移性RCC患者。收集临床特征，并从基线石蜡包埋肿瘤样本中确定VHL基因（VHL）的激活状态。记录肿瘤反应、肿瘤进展时间（TTP）和总生存期。
43例患者可评估VHL状态和临床反应。18例患者（43%；95%置信区间28 - 59%）出现客观反应。整个队列的中位TTP为8.1个月。具有以下临床特征的患者临床结局较好：男性、无肝转移、既往未接受过放疗以及基线血红蛋白水平较高。26例患者（60%）有VHL突变或启动子甲基化证据；此类患者的客观反应率为48%，而无VHL突变或甲基化的患者为35%。具有VHL甲基化或预测会截断或改变VHL阅读框的突变的患者，中位TTP为13.3个月，而无这些特征的患者为7.4个月（P = 0.06）。
VEGF靶向治疗在转移性RCC中有效，且反应可能与某些临床特征相关。VHL甲基化或发生截断或改变VHL阅读框的突变的患者，VEGF靶向治疗的TTP可能会延长。需要进一步研究VHL通路成分，以了解转移性RCC对VEGF靶向药物反应的生物学机制。
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