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在使用血管内皮生长因子受体酪氨酸激酶抑制剂(VEGFR-TKI)和雷帕霉素靶蛋白(mTOR)抑制剂治疗失败后,对转移性肾细胞癌患者进行VEGFR-TKI再挑战治疗。

Vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) rechallenge for patients with metastatic renal cell carcinoma after treatment failure using both VEGFR-TKI and mTOR inhibitor.

作者信息

Park Inkeun, Lee Jae-Lyun, Ahn Jin-Hee, Lee Dae-Ho, Lee Kyoo-Hyung, You Dalsan, Jeong In Gab, Song Cheryn, Hong Bumsik, Hong Jun Hyuk, Ahn Hanjong

机构信息

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.

出版信息

Cancer Chemother Pharmacol. 2015 May;75(5):1025-35. doi: 10.1007/s00280-015-2725-8. Epub 2015 Mar 17.

Abstract

PURPOSE

To assess the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) rechallenge for metastatic renal cell carcinoma (mRCC) patients and to identify predictive factors for increased progression-free survival (PFS) or overall survival (OS).

METHODS

The clinicopathological features, outcomes, and prognostic factors of mRCC patients who were treated with VEGFR-TKI after treatment failure using both VEGFR-TKIs and mTOR inhibitors (mTORi) were reviewed.

RESULTS

A total of 29 eligible patients were included. Five (17 %) patients achieved partial response (PR) with a median response duration of 9.5 months (95 % CI 5.7-13.4 months), and additional 16 patients (55 %) achieved stable disease. With a median follow-up period of 19.2 months (95 % CI 18.9-19.6 months), the median PFS and OS were 3.0 months (95 % CI 1.1-4.9 months) and 4.9 months (95 % CI 2.9-6.8 months), respectively. In univariate analysis, the best response to first-line VEGFR-TKI (PR vs. non-PR, p < 0.001) and time to rechallenge (TTR, ≤12 months vs. between 12 and 24 months vs. >24 months, p = 0.005) were identified as predictive factors for longer PFS on VEGFR-TKI rechallenge. In addition, an MSKCC risk group (intermediate- vs. poor-risk group, p = 0.027), better response at first-line VEGFR-TKI (PR vs. non-PR, p = 0.003), and TTR (≤12 months vs. between 12 and 24 months vs. >24 months, p = 0.026) were identified as prognostic factors for longer OS.

CONCLUSIONS

VEGFR-TKI rechallenge may be a viable option for select metastatic RCC patients who fail both VEGFR-TKI and mTORi therapies.

摘要

目的

评估血管内皮生长因子受体酪氨酸激酶抑制剂(VEGFR-TKI)再次治疗转移性肾细胞癌(mRCC)患者的疗效,并确定无进展生存期(PFS)或总生存期(OS)延长的预测因素。

方法

回顾了在使用VEGFR-TKIs和mTOR抑制剂(mTORi)治疗失败后接受VEGFR-TKI治疗的mRCC患者的临床病理特征、结局和预后因素。

结果

共纳入29例符合条件的患者。5例(17%)患者获得部分缓解(PR),中位缓解持续时间为9.5个月(95%CI 5.7-13.4个月),另外16例患者(55%)病情稳定。中位随访期为19.2个月(95%CI 18.9-19.6个月),中位PFS和OS分别为3.0个月(95%CI 1.1-4.9个月)和4.9个月(95%CI 2.9-6.8个月)。单因素分析中,一线VEGFR-TKI的最佳反应(PR与非PR,p<0.001)和再次治疗时间(TTR,≤12个月与12至24个月与>24个月,p=0.005)被确定为VEGFR-TKI再次治疗时PFS延长的预测因素。此外,MSKCC风险组(中危与低危组,p=0.027)、一线VEGFR-TKI时更好的反应(PR与非PR,p=0.003)和TTR(≤12个月与12至24个月与>24个月,p=0.026)被确定为OS延长的预后因素。

结论

对于VEGFR-TKI和mTORi治疗均失败的部分转移性RCC患者,VEGFR-TKI再次治疗可能是一种可行的选择。

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