Prof. Dr. George Hempel, Institute of Pharmacology and Medicinal Chemistry, University of MΓΌnster
Tuesday 31st January, 1.00 p.m., Stacey Lecture Theatre 1
The dosing of anti-cancer drugs in children relies mainly on clinical experience. Systematic investigations of the pharmacokinetics (drug absorption, body distribution, metabolism, excretion) and pharmacodynamics (drug effects on an organism including diseased and healthy tissues) of anti-cancer drugs in children are largely missing. Here, we studied the pharmacokinetics and pharmacodynamics of doxorubicin, one of the most frequently used anti-cancer drugs, in a study conducted in 20 European hospitals that included 100 children.
Most notably, a reduced clearance of doxorubicin was found in younger children. Cardiotoxicity is a major side effect of anthracyclins like doxorubicin. Troponins and natriuretic peptides, biomarkers that indicate doxorubicin-induced cardiotoxicity, were elevated in most patients after treatment. However, no clear correlation between the individual doxorubicin pharmacokinetics and the levels of troponins and natriuretic peptides was found. A new dosing algorithms that better reflects the effects of age and size on the pharmacokinetics and pharmacodynamics of doxorubicin and other cytostatics is currently under development. This will result in more individualised therapy regimens with the aim to increase efficacy and to reduce toxic adverse events.