Huitema Group

Group leader: Prof. dr. Alwin Huitema

Precision dosing

The focus of the Huitema group is precision dosing of anticancer drugs and drugs used in supportive care in pediatric oncology. This is an essential part of precision medicine and aims at delivering the right dose to each patient. To achieve this aim, pharmacological studies are initiated and/or embedded in (early) clinical trials and translation research. The research group is strongly associated with the Pharmacy at the Princess Máxima Center.

"The right dose for each child" Prof. dr. Alwin Huitema - Group leader

Pharmacology in early clinical trials

In collaboration with the Zwaan group, pharmacological research is integrated in early clinical trials in children. Dose finding of novel anticancer agents in children is complex and requires multidisciplinary input including pharmacokinetic and pharmacodynamic data including translation of adult knowledge to children. Input from clinical pharmacists from the Princess Máxima Center ensures coherence with clinical practice. Many of these studies are conducted in multicenter networks such as ITCC.

Optimal dosing of anticancer drugs in infants

In the PINOCCHIO study, pharmacokinetic data is obtained from several anticancer drugs in children with a special focus on infants. These data will be used to develop evidence-based dosing guidelines of these agents in infants. This study is conducted in collaboration with the Zwaan group. Comprehensive clinical care is instituted by interaction of the clinical pharmacists with the reseach group, translating pharmacological issues in clinical care to research questions and vice versa. To support, the PATIO study has also been opened recently, a pharmacokinetics study on the anticancer treatment for acute lymphoblastic leukemia in infants.

Pharmacogenetics and pharmacogenomics

Another important explanation for the variety in drug response is the genetic variation in children. Pharmacogenetics and pharmacogenomics (PGx) is the study on how genetic variants could predict a person’s response to a drug. Pharmacogenetic testing can be a useful tool to select the most appropriate treatment for an individual patient, tailored to his or her genetic predisposition. Using existing whole genome sequencing (WGS) data, drug-gene interactions are analyzed prospectively. Eventually, this results in practical evidence-based guidelines for pediatricians to perform pre-emptive genotyping for chemotherapy and supportive care drugs in pediatric oncology.

Drug assays for pediatric oncology

Measuring blood concentrations is essential to describe the kinetics of a drug. Drug assays to measure drug concentrations offer important research results and serve as a basis for drug development in children. Moreover, it helps in converting adult drug applications into pediatrics. And, once a drug is used in children, it may be important to check whether the child has the required amount of the drug in the blood, or whether it needs modification to optimize therapy.

Other pharmacology topics

Pharmacological studies are a part of many ongoing research programs. Examples of ongoing studies are:

• Pharmacology within the hematopoietic stem cell transplantation and CAR-T program
• Development of novel pediatric dosage forms of anticancer agents
• PK/PD of agents used in supportive care

Collaborations

The Huitema Group has a strong collaboration with the University Medical Center Utrecht (UMCU). Several PhD students perform their projects in a joint effort of both pharmacies. Members of the Huitema group join the regular research meetings of the UMCU pharmacy. 

We also collaborate with the Department of Pharmacy & Pharmacology of the Netherlands Cancer Institute (NKI) with regard to clinical pharmacology of anticancer agents. The Princess Máxima Center and the NKI are the only centers in the Netherlands that are fully specialized in cancer care and research and offer highly specialized care with a fine line between research and care. The facilities, knowledge and experience of the two institutions are complementary to each other and highly specialized. This gives a great opportunity for synergy.

In addition, the first studies at the in-house Drug Analysis Lab have started. In collaboration with the Heidenreich group, it is being examined whether it is possible to determine the amount of siRNA, and a KiKa project with Shunya Ohmura and Thomas Grunewald from the German KiTZ/DKFZ in Heidelberg has started, where it is investigated whether the existing drug disulfiram for adults can be repurposed for children with Ewing's sarcoma by attaching a copper atom to it. For this purpose, analysts are investigating whether the amount of disulfiram and copper in the tumor and healthy tissue can be measured with LC-MSMS.

Concerning pharmacogenetics we collaborate with the bio-informaticians of the Kemmeren group. We work together intensively to utilize the available genetic pipeline for relevant variations in the context of pharmacology.