肾功能的治疗相关恶化与舒尼替尼对转移性肾细胞癌患者的抗肿瘤疗效相关。

Treatment-related deterioration of renal function is associated with the antitumor efficacy of sunitinib in patients with metastatic renal cell carcinoma.

作者信息

Fukuda Hironori, Kondo Tsunenori, Iida Shoichi, Takagi Toshio, Tanabe Kazunari

机构信息

Department of Urology, Tokyo Women׳s Medical University, Tokyo, Japan.

出版信息

Urol Oncol. 2016 Aug;34(8):338.e1-9. doi: 10.1016/j.urolonc.2016.03.010. Epub 2016 Apr 13.

DOI:10.1016/j.urolonc.2016.03.010

PMID:27085488

Abstract

OBJECTIVES

Some "on-target" adverse events, such as hypertension and thrombocytopenia, have been reported to predict the antitumor efficacy of sunitinib as first-line therapy in patients with metastatic renal cell carcinoma (mRCC). However, it is unclear whether the degree of deterioration of renal function resulting from inhibition of the vascular endothelial growth factor signaling pathway can predict the antitumor efficacy of sunitinib. Therefore, the aim of the present study was to investigate whether the degree of deterioration of renal function can predict the antitumor efficacy of sunitinib in patients with mRCC.

MATERIALS AND METHODS

The present study retrospectively reviewed the medical records of patients with histologically confirmed mRCC who were treated with sunitinib for>3 months between March 2008 and September 2014. The degree of deterioration of the estimated glomerular filtration rate (eGFR) and the progression-free survival (PFS) and overall survival (OS) were compared.

RESULTS

The study included 62 patients with mRCC. The 62 study patients were divided into the following 2 subgroups according to whether they had a≥10% decrease in the eGFR during sunitinib therapy: Group 1 (≥10% decrease in the eGFR, N = 47 [76%]) and Group 2 (<10% decrease in the eGFR, N = 15 [24%]). PFS was significantly longer in Group 1 than in Group 2 (16mo vs. 6mo, P = 0.001). In multivariate analysis, the Memorial Sloan-Kettering Cancer Center risk group (favorable vs. intermediate, hazard ratio [HR] = 3.7; favorable vs. poor, HR = 14.7, P = 0.05), number of sunitinib courses (HR = 0.64, P<0.0001), baseline eGFR (HR = 0.96, P = 0.0057), and a≥10% decrease in the eGFR (HR = 3.2, P = 0.017) were identified as independent predictors of PFS. In addition, the OS was significantly longer in Group 1 than in Group 2 (not reached vs. 13mo, P = 0.034). In multivariate analysis, a≥10% decrease in the eGFR (HR = 0.98, P = 0.97) was not identified as an independent predictor of OS.

CONCLUSIONS

The degree of deterioration of renal function might predict the antitumor efficacy of sunitinib in patients with mRCC.

摘要

目的

据报道，一些“靶向”不良事件，如高血压和血小板减少症，可预测舒尼替尼作为转移性肾细胞癌（mRCC）患者一线治疗的抗肿瘤疗效。然而，尚不清楚血管内皮生长因子信号通路抑制导致的肾功能恶化程度是否能预测舒尼替尼的抗肿瘤疗效。因此，本研究的目的是调查肾功能恶化程度是否能预测mRCC患者中舒尼替尼的抗肿瘤疗效。

材料与方法

本研究回顾性分析了2008年3月至2014年9月期间接受舒尼替尼治疗超过3个月的经组织学确诊的mRCC患者的病历。比较了估计肾小球滤过率（eGFR）的恶化程度与无进展生存期（PFS）和总生存期（OS）。

结果

该研究纳入了62例mRCC患者。根据舒尼替尼治疗期间eGFR是否下降≥10%，将62例研究患者分为以下2个亚组：第1组（eGFR下降≥10%，N = 47 [76%]）和第2组（eGFR下降<10%，N = 15 [24%]）。第1组的PFS显著长于第2组（16个月对6个月，P = 0.001）。在多变量分析中，纪念斯隆凯特琳癌症中心风险组（良好对中等，风险比[HR] = 3.7；良好对不良，HR = 14.7，P = 0.05）、舒尼替尼疗程数（HR = 0.64，P<0.0001）、基线eGFR（HR = 0.96，P = 0.0057）以及eGFR下降≥10%（HR = 3.2，P = 0.017）被确定为PFS的独立预测因素。此外，第1组的OS显著长于第2组（未达到对13个月，P = 0.034）。在多变量分析中，eGFR下降≥10%（HR = 0.98，P = 0.97）未被确定为OS的独立预测因素。