Portal de Periódicos da CAPES

Intrinsic resistance to sunitinib in patients with metastatic renal cell carcinoma

2016; Wiley; Volume: 13; Issue: 1 Linguagem: Inglês

10.1111/ajco.12465

1743-7563

Sung Hee Lim, In Gyu Hwang, Jun Ho Ji, Sung Yong Oh, Jun Ho Yi, Do Hyoung Lim, Ho Yeong Lim, Su Jin Lee, Se Hoon Park,

Pancreatic and Hepatic Oncology Research

Asia-Pacific Journal of Clinical OncologyVolume 13, Issue 1 p. 61-67 Original article Intrinsic resistance to sunitinib in patients with metastatic renal cell carcinoma Sung Hee Lim, Sung Hee Lim Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaSearch for more papers by this authorIn Gyu Hwang, In Gyu Hwang Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, KoreaSearch for more papers by this authorJun Ho Ji, Jun Ho Ji Department of Hematology-Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, KoreaSearch for more papers by this authorSung Yong Oh, Sung Yong Oh Division of Hematology-Oncology, Dong-A University, College of Medicine, Seoul, KoreaSearch for more papers by this authorJun Ho Yi, Jun Ho Yi Division of Hematology-Oncology, Department of Medicine, Hanyang University Hospital, Seoul, KoreaSearch for more papers by this authorDo Hyoung Lim, Do Hyoung Lim Division of Hematology and Oncology, Department of Medicine, Dankook University Hospital, Cheonan, KoreaSearch for more papers by this authorHo Yeong Lim, Ho Yeong Lim Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaSearch for more papers by this authorSu Jin Lee, Su Jin Lee Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaSearch for more papers by this authorSe Hoon Park, Corresponding Author Se Hoon Park hematoma@skku.edu Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaCorrespondence: Se Hoon Park MD PhD, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135–710, Korea. Email: hematoma@skku.eduSearch for more papers by this author Sung Hee Lim, Sung Hee Lim Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaSearch for more papers by this authorIn Gyu Hwang, In Gyu Hwang Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, KoreaSearch for more papers by this authorJun Ho Ji, Jun Ho Ji Department of Hematology-Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, KoreaSearch for more papers by this authorSung Yong Oh, Sung Yong Oh Division of Hematology-Oncology, Dong-A University, College of Medicine, Seoul, KoreaSearch for more papers by this authorJun Ho Yi, Jun Ho Yi Division of Hematology-Oncology, Department of Medicine, Hanyang University Hospital, Seoul, KoreaSearch for more papers by this authorDo Hyoung Lim, Do Hyoung Lim Division of Hematology and Oncology, Department of Medicine, Dankook University Hospital, Cheonan, KoreaSearch for more papers by this authorHo Yeong Lim, Ho Yeong Lim Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaSearch for more papers by this authorSu Jin Lee, Su Jin Lee Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaSearch for more papers by this authorSe Hoon Park, Corresponding Author Se Hoon Park hematoma@skku.edu Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaCorrespondence: Se Hoon Park MD PhD, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135–710, Korea. Email: hematoma@skku.eduSearch for more papers by this author First published: 31 March 2016 https://doi.org/10.1111/ajco.12465Citations: 14 Conflicts of interest: none. Competing interests: There is no competing interest. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Aim Although targeting angiogenesis with vascular endothelial growth factor receptor (VEGFR) inhibitors has demonstrated efficacy in the treatment of renal cell carcinoma, primary, intrinsic resistance to the VEGFR inhibitor sunitinib is not fully understood in a subset of metastatic RCC (mRCC) patients. Methods Between 2008 and 2012, a total of 134 patients with mRCC were treated with first-line sunitinib at one of six tertiary centers. Patients in whom progressive disease was the best response were classified as the intrinsic resistance group. Univariate and multivariate analyses were performed on the recognized baseline parameters. Results Among 134 patients, 33 (25%) intrinsically resistant to sunitinib were identified. Multivariate logistic regression analyses revealed that the number of metastatic sites (OR = 3.6) and neutrophilia (OR = 7.4) were independently associated with development of intrinsic resistance. There were significant differences with regard to overall survival (P = 0.001) and progression-free survival (P < 0.0001) between the patients with and without intrinsic resistance. Conclusions Intrinsic resistance to first-line sunitinib treatment is associated with a dismal prognosis in mRCC patients. Patients with known high-risk factors (poor performance, neutrophilia, elevated lactate dehydrogenase) and multiple metastatic sites including the liver may experience a limited benefit from sunitinib. Greater understanding of the underlying mechanism and molecular biomarkers for detecting intrinsically resistant disease is needed. Citing Literature Supporting Information Disclaimer: Supplementary materials have been peer-reviewed but not copyedited. Filename Description ajco12465-sup-0001-FigureS1.tif145.1 KB Figure S1. Comparison of progression-free survival for patients who received second-line treatment after progression to sunitinib between intrinsic resistance and non-intrinsic resistance group. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume13, Issue1February 2017Pages 61-67 RelatedInformation