Serum Lactate Dehydrogenase Predicts for Overall Survival Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Inhibition of Mammalian Target of Rapamycin
Serum Lactate Dehydrogenase Predicts for Overall Survival Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Inhibition of Mammalian Target of Rapamycin
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DOI：
10.1200/jco.2011.40.9631
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发表时间：
2012-09-20
影响因子：
45.3
通讯作者：
Halabi, Susan
中科院分区：
文献类型：
--
作者：
Armstrong, Andrew J.;George, Daniel J.;Halabi, Susan
目的乳酸脱氢酶（LDH）是一种参与无氧糖酵解的酶，受磷脂酰肌醇3-激酶/Akt/哺乳动物雷帕霉素靶蛋白复合物1（PI 3 K/Akt/TORC 1）通路以及肿瘤缺氧/坏死的调节。高血清LDH水平与包括肾细胞癌（RCC）在内的癌症患者的不良预后相关。我们测试了血清LDH是否是预后和转移性肾细胞癌患者接受mTOR inhibitors.Patients和MethodsWe的预测价值评估治疗前和治疗后的血清LDH在404低风险肾细胞癌患者与TORC 1抑制剂替西罗莫司或干扰素α治疗的国际III期随机试验。比例风险模型被用来测试LDH在预测总生存期（OS）的预后和预测关联。结果平均基线血清标准化LDH是1.23倍正常上限（ULN;范围，0.05至28.5 × ULN）。LDH> 1 x ULN的患者与LDH> 1 x ULN的患者相比，死亡的多变量风险比为2.81（95% CI，2.01 - 3.94; P < .001）。
PurposeLactate dehydrogenase (LDH) is an enzyme involved in anaerobic glycolysis and regulated by the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR)-containing complex 1 (PI3K/Akt/TORC1) pathway as well as tumor hypoxia/necrosis. High serum LDH levels are associated with poor prognosis in patients with cancer, including renal cell carcinoma (RCC). We tested whether serum LDH is prognostic and has predictive value in patients with metastatic RCC receiving an mTOR inhibitor.Patients and MethodsWe evaluated pretreatment and post-treatment serum LDH in 404 poor-risk patients with RCC treated with the TORC1 inhibitor temsirolimus or interferon alfa in an international phase III randomized trial. The proportional hazards model was used to test for the prognostic and predictive association of LDH in predicting overall survival (OS).ResultsMean baseline serum normalized LDH was 1.23 times the upper limit of normal (ULN; range, 0.05 to 28.5 x ULN). The multivariable hazard ratio for death was 2.81 (95% CI, 2.01 to 3.94; P < .001) for patients with LDH more than 1 x ULN versus patients with LDH