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Asia Pac J Clin Oncol. 2017 Feb;13(1):61-67. doi: 10.1111/ajco.12465. Epub 2016 Mar 31.

Intrinsic resistance to sunitinib in patients with metastatic renal cell carcinoma.

Author information

1
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2
Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
3
Department of Hematology-Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
4
Division of Hematology-Oncology, Dong-A University, College of Medicine, Seoul, Korea.
5
Division of Hematology-Oncology, Department of Medicine, Hanyang University Hospital, Seoul, Korea.
6
Division of Hematology and Oncology, Department of Medicine, Dankook University Hospital, Cheonan, Korea.

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.

KEYWORDS:

intrinsic resistance; prognosis; renal cell carcinoma; sunitinib

PMID:
27030134
DOI:
10.1111/ajco.12465
[Indexed for MEDLINE]

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