DPOG TDM

Aim of the project

During the treatment with oral anticancer drugs individuals have a high risk to be underdosed (>30% of the patients), which could lead to a decrease in anti-tumor efficacy, or overdosed (>15% of the patients), which could lead to increase in side effects.1-5 By implementing Therapeutic Drug Monitoring we try to personalize the dosing of the anti-cancer treatment to reach to most optimal dose for each individual. 

Therapeutic drug monitoring

Therapeutic drug monitoring (TDM) is a well-established way of personalizing the dose of a drug based on measured drug levels in blood.6 Blood is collected during treatment, drug levels are determined and are used to guide further dosing. The aim of TDM is to establish the optimal dose for each individual patient taking into account important patient and treatment characteristics, as co-medication, co-morbidity and measured drug concentrations. TDM is a well-established method for personalized dosing of drugs and is broadly used in the field of transplantation medicine or treatment of micro-organisms. 

Execution of the project

For most oral anticancer drugs, blood samples will be taken at 4, 8 and 12 weeks after start of treatment to measure the concentration of the drug in the blood of the patient. Based on this concentration and patient characteristics an advise on the dosing of the treatment will be given to the treating physician. Together with the patient the treating physician will discuss the recommendation and possibly implement it. After 4 weeks the intervention will be evaluated and if necessary further improved. After 12 weeks the aim is to reach the most optimal dose for the individual patient. Every 12 weeks there after the dose will be monitored and if necessary improved.

The aim of this project is to perform a prospective study implementing TDM of oral targeted anti-cancer drugs in multiple large hospitals in the Netherlands and to build a prospective registry to structurally collect data on the patients’ clinical outcome and the effectiveness of the interventions.

This project is partly funded by unrestricted grants by Novartis, Roche and Pfizer.

Collaboration within Erasmus MC:

This project is performed by the department of Medical Oncology in collaboration with the department of Pharmacy.

Collaboration outside Erasmus MC:

This project is an initiative of the Dutch Pharmacology Oncology Group (DPOG) which is a collaboration between the following institutions:

• Erasmus MC Cancer Institute
• Netherlands Cancer Institute – Antoni van Leeuwenhoek
• Leiden University Medical Center
• Radboud University Medical Center
• University Medical Center Groningen

• Verheijen RB, Bins S, Mathijssen RHJ, Lolkema MP, van Doorn L, Schellens JHM, et al. Individualized Pazopanib Dosing: A Prospective Feasibility Study in Cancer Patients.
• Lankheet N, Kloth J, Gadellaa-van Hooijdonk C, Cirkel G, Mathijssen R, Lolkema M, et al. Pharmacokinetically guided sunitinib dosing: a feasibility study in patients with advanced solid tumours.  
• Lankheet N, Knapen L, Schellens J, Beijnen J, Steeghs N, Huitema A. Plasma concentrations of tyrosine kinase inhibitors imatinib, erlotinib, and sunitinib in routine clinical outpatient cancer care.
• Yu H, Steeghs N, Nijenhuis C, Schellens J, Beijnen J, Huitema A. Practical guidelines for therapeutic drug monitoring of anticancer tyrosine kinase inhibitors: Focus on the pharmacokinetic targets.
• Van Leeuwen R, van Gelder T, Mathijssen R, Jansman F. Drug-drug interactions with tyrosine-kinase inhibitors: A clinical perspective.
• Groenland SL, van Eerden RAG, Verheijen RB, Koolen SLW, Moes DJAR, Desar IME, Reyners AKL, Gelderblom HJ, van Erp NP, Mathijssen RHJ, Huitema ADR, Steeghs N. Therapeutic Drug Monitoring of Oral Anticancer Drugs: The Dutch Pharmacology Oncology Group-Therapeutic Drug Monitoring Protocol for a Prospective Study.

• Prof. A.H.J. (Ron) Mathijssen, principal investigator
• Dr. L.W. (Stijn) Koolen
• A.G. (Ruben) van Eerden

Contact us:

r.vaneerden@erasmusmc.nl