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Eur J Clin Pharmacol. 2015 Dec;71(12):1477-84. doi: 10.1007/s00228-015-1935-7. Epub 2015 Sep 21.

Association of single nucleotide polymorphisms in IL8 and IL13 with sunitinib-induced toxicity in patients with metastatic renal cell carcinoma.

Author information

1
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333ZA, Netherlands.
2
Dutch SUTOX consortium, Leiden, Netherlands.
3
Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China.
4
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333ZA, Netherlands. j.j.swen@lumc.nl.
5
Dutch SUTOX consortium, Leiden, Netherlands. j.j.swen@lumc.nl.
6
Department of Medical Oncology, VU University Medical Center, Amsterdam, Netherlands.
7
Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
8
Spanish Oncology Genitourinary Group (SOGUG), Madrid, Spain.
9
Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands.
10
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
11
Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
12
ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
13
Oncology Unit, Clara Campal Comprehensive Cancer Center, Madrid, Spain.
14
Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute (CCF), Cleveland, OH, USA.

Abstract

PURPOSE:

Earlier, the association of single nucleotide polymorphisms (SNPs) with toxicity and efficacy of sunitinib has been explored in patients with metastatic renal cell carcinoma (mRCC). Recently, additional SNPs have been suggested as potential biomarkers. We investigated these novel SNPs for association with sunitinib treatment outcome in mRCC patients.

METHODS:

In this exploratory study, we selected SNPs in genes CYP3A4, NR1I2, POR, IL8, IL13, IL4-R, HIF1A and MET that might possibly be associated with sunitinib treatment outcome. Each SNP was tested for association with progression-free survival (PFS) and overall survival (OS) by Cox-regression analysis and for clinical response and toxicity using logistic regression.

RESULTS:

We included 374 patients for toxicity analyses, of which 38 patients with non-clear cell renal cell cancer were excluded from efficacy analyses. The risk for hypertension was increased in the presence of the T allele in IL8 rs1126647 (OR = 1.69, 95 % CI = 1.07-2.67, P = 0.024). The T allele in IL13 rs1800925 was associated with an increase in the risk of leukopenia (OR = 6.76, 95 % CI = 1.35-33.9, P = 0.020) and increased prevalence of any toxicity > grade 2 (OR = 1.75, 95 % CI = 1.06-2.88, P = 0.028). No significant associations were found with PFS, OS or clinical response.

CONCLUSIONS:

We show that polymorphisms in IL8 rs1126647 and IL13 rs1800925 are associated with sunitinib-induced toxicities. Validation in an independent cohort is required.

KEYWORDS:

Metastatic renal cell carcinoma; Progression-free survival; Single nucleotide polymorphism; Sunitinib; Toxicity; Tyrosine kinase inhibitor

PMID:
26387812
PMCID:
PMC4643117
DOI:
10.1007/s00228-015-1935-7
[Indexed for MEDLINE]
Free PMC Article

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