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Optimization of sunitinib treatment in metastatic renal cell carcinoma : pharmacogenetic evidence and challenges
Sunitinib has been approved by FDA in 2006 and became the first-line treatment for patients with clear cell metastatic renal cell carcinoma (cc-mRCC) due to its dramatic improvement in progression-free survival (PFS) and overall survival (OS) and affordable toxicity. However, the inter-individual variability of sunitinib outcomes is large. Some clinical factors, such as blood pressure, can partly predict sunitinib efficacy, but they are not enough. More insight into the genetic factors underlying sunitinib outcome could also be helpful to improve optimization of treatment. In this thesis, the relevance of single nucleotide polymorphisms (SNPs) to sunitinib treatment in (cc)-mRCC patients was investigated with regard to efficacy and toxicity.We identified SNPs in IL8,IL13, VEGFR, CYP3A5 and CTLA-4 were associated with efficacy, toxicity and clearance.Further validation in independent cohorts is need before the implementation of...
Show moreSunitinib has been approved by FDA in 2006 and became the first-line treatment for patients with clear cell metastatic renal cell carcinoma (cc-mRCC) due to its dramatic improvement in progression-free survival (PFS) and overall survival (OS) and affordable toxicity. However, the inter-individual variability of sunitinib outcomes is large. Some clinical factors, such as blood pressure, can partly predict sunitinib efficacy, but they are not enough. More insight into the genetic factors underlying sunitinib outcome could also be helpful to improve optimization of treatment. In this thesis, the relevance of single nucleotide polymorphisms (SNPs) to sunitinib treatment in (cc)-mRCC patients was investigated with regard to efficacy and toxicity.We identified SNPs in IL8,IL13, VEGFR, CYP3A5 and CTLA-4 were associated with efficacy, toxicity and clearance.Further validation in independent cohorts is need before the implementation of these genetic biomarkers into clinical practice.
Show less- All authors
- Liu, X.
- Supervisor
- Guchelaar, H.-J.
- Co-supervisor
- Swen, J.J.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Medicine / Leiden University Medical Center (LUMC) , Leiden University
- Date
- 2018-05-15
- ISBN (print)
- 9789492026149
Funding
- Sponsorship
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center