Focus of research
[Forschungslinie 2]: Pharmacometric data analysis
“Population Pharmacokinetic/Pharmacodynamic Modelling of Myelotoxicity”
Anticancer drugs are often associated with myelotoxicity, in particular reduction of neutrophils (neutropenia) which is one of the most important dose-limiting adverse events in many anticancer treatment options. Especially patients receiving high-dose chemotherapy exhibit severe neutropenia. The major fatal complication of acute neutropenia is the occurrence of severe infections which are quantitatively related to the degree and the duration of neutropenia.
Hence, mechanism-based models that can describe and predict both the degree and the duration of neutropenia as haematological toxicity are of particular interest.
Mechanistic pharmacokinetic/pharmacodynamic (PK/PD) models describe the maturation of haematopoietic cells under the impact of myelotoxic drugsin patients. These models are built in order to combine the pharmacokinetic profiles of chemotherapeutic drugs and the time course of the resulting neutropenia.
Simulations should help to explore the contribution of the single drugs of anti-cancer regimens to myelosuppression and to to investigate the benefit ofperipheral blood stem cell retransfusion (PBSCT) and granulocyte-colony stimulating factor G-CSF administration as a stem cell rescue to circumvent this adverse event in particular.
As semi-mechanistic models make it possible to differentiate between system-related and drug-specific parameters, goal of my PhD thesis is to explore drug-related parameters for their use in PK/PD modelling and prediction of neutropenia. In combination with efficacy, these models shall contribute to evaluate clinical benefit/risk ratios in the management of cancer patients.