PhD defence G.D.M. (Marijn) Veerman

Summary:

Tyrosine kinase inhibitors (TKIs) are used to target certain forms of metastatic lung cancer. If a treatable genetic alteration is demonstrated after pathological examination, treatment with TKIs is preferable to classical chemotherapy or immunotherapy. TKIs are tablets to be taken daily. Using TKIs has increased the survival time and quality of life of the overall patient group. 

However, there are also patients where TKIs have no effect or serious (life-threatening) side effects occur. Many factors influence this, including pharmacokinetics. This refers to the processes of absorption, distribution, metabolism and excretion of drugs. Pharmacokinetics ensures a certain exposure of the TKI to the body and tumours. This exposure varies between individuals (interpatient variability), but also within an individual (intrapatient variability). For every drug, there is an area of exposure within which the drug is effective, and no serious side effects occur: the therapeutic window. This optimal balance can be pursued for each patient (personalised) for the best possible treatment of his or her lung cancer. The studies in this thesis aim to improve the pharmacological personalisation of TKIs.