Abstract
PurposeEarlier, 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.MethodsIn 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.ResultsWe 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.ConclusionsWe show that polymorphisms in IL8 rs1126647 and IL13 rs1800925 are associated with sunitinib-induced toxicities. Validation in an independent cohort is required.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-015-1935-7) contains supplementary material, which is available to authorized users.
Highlights
Several targeted therapies have been approved for the treatment of metastatic renal cell carcinoma
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)
Summary
Several targeted therapies have been approved for the treatment of metastatic renal cell carcinoma (mRCC). The tyrosine kinase inhibitor (TKI) sunitinib is widely used as first-line treatment option [1–4]. The response to sunitinib varies largely among patients. 35 % of mRCC patients benefit from sunitinib, and about 30 % of patients need dose reductions due to adverse events of which grades vary among patients [1, 5, 6]. To optimize treatment efficacy and to minimize the risk of adverse events of higher grades, it would be helpful to predict the individual treatment outcome at the initiation of therapy. No biomarkers are yet available to fulfil this need
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