Refining EGFR-monoclonal antibody treatment in colorectal cancer

Author(s):
Krens, L.L.
Published
2015
Publication type
Doctoral Thesis

Abstract

The use of the epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab is limited to colorectal cancer (CRC) patients with KRAS wild type tumors and more recently in RAS wild type only. After having become chemotherapy refractory, treatment options are limited for this substantial patient group. This means that there is an urgent need to optimize anti-EGFR therapy. The work presented in this thesis aimed at optimising EGFR targeted monoclonal antibody therapy in metastatic CRC. This thesis investigates several strategies to refine EGFR targeted monoclonal antibody therapy in CRC by: 1. statins and their ability to phenoconvert KRAS mutant CRC; __ 2. exploration of polymorphisms in the gene encoding FCGR3A and their association __with cetuximab efficacy; __ 3. and investigating the pharmacokinetics of cetuximab and panitumumab in patients with renal or hepatic dysfunction. __

Organ dysfuctionKRASFCGR3APanitumumabCetuximabMetastatic colorectal cancerEGFR-antibodies
Defense date
2015-07-02
Language
English
Supervisor(s)
Guchelaar, H.-J.; Gelderblom, A.J.
Advisor(s)
Straaten, R.J.H.M. van der
Qualification
Ph.D.
Degree granting institution
Department of Clinical Pharmacy and Toxicology and Clinical Oncology, Faculty of Medicine (LUMC), Leiden University, Leiden
hdl
1887/33832
ISBN(s)
97894920260507