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Eur Urol. 2014 Apr;65(4):723-30. doi: 10.1016/j.eururo.2013.10.013. Epub 2013 Oct 26.

The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Cancer Database Consortium.

Author information

1
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
2
Aarhus University Hospital, Aarhus, Denmark.
3
Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
4
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
5
Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA.
6
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
7
City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
8
Stanford Medical Center, Stanford, CA, USA.
9
British Columbia Cancer Agency, Vancouver, BC, Canada.
10
Cross Cancer Institute, Edmonton, AB, Canada.
11
Dalhousie University, Halifax, NS, Canada.
12
Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
13
National Cancer Centre Singapore, Singapore.
14
London Regional Cancer Program, London, ON, Canada.
15
Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
16
Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
17
Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
18
Tom Baker Cancer Center, Calgary, AB, Canada.
19
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: toni_choueiri@dfci.harvard.edu.

Abstract

BACKGROUND:

Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients treated with immunotherapy.

OBJECTIVE:

To investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium.

DESIGN, SETTING, AND PARTICIPANTS:

Data on 1661 patients treated with first-line vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy for mRCC were available from 18 cancer centers to study the impact of hyponatremia (serum sodium level <135 mmol/l) on clinical outcomes.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

The primary objective was overall survival (OS) and secondary end points included time to treatment failure (TTF) and the disease control rate (DCR). The chi-square test was used to compare the DCR in patients with and without hyponatremia. OS and TTF were estimated with the Kaplan-Meier method and differences between groups were examined by the log-rank test. Multivariable logistic regression (for DCR) and Cox regression (for OS and TTF) were undertaken adjusted for prognostic risk factors.

RESULTS AND LIMITATIONS:

Median OS after treatment initiation was 18.5 mo (95% confidence interval [CI], 17.5-19.8 mo), with 552 (33.2%) of patients remaining alive on a median follow-up of 22.1 mo. Median baseline serum sodium was 138 mmol/l (range: 122-159 mmol/l), and hyponatremia was found in 14.6% of patients. On univariate analysis, hyponatremia was associated with shorter OS (7.0 vs 20.9 mo), shorter TTF (2.9 vs 7.4 mo), and lower DCR rate (54.9% vs 78.8%) (p<0.0001 for all comparisons). In multivariate analysis, these effects remain significant (hazard ratios: 1.51 [95% CI, 1.26-1.80] for OS, and 1.57 [95% CI, 1.34-1.83] for TTF; odds ratio: 0.50 [95% CI, 34-0.72] for DCR; adjusted p<0.001). Results were similar if sodium was analyzed as a continuous variable (adjusted p<0.0001 for OS, TTF, and DCR).

CONCLUSIONS:

This is the largest multi-institutional report to show that hyponatremia is independently associated with a worse outcome in mRCC patients treated with VEGF- and mTOR-targeted agents.

KEYWORDS:

Anti-VEGF; Hyponatremia; Prognostic factors; Renal cell cancer

PMID:
24184025
PMCID:
PMC4142674
DOI:
10.1016/j.eururo.2013.10.013
[Indexed for MEDLINE]
Free PMC Article

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