PhD defence N.A.D. (Niels) Guchelaar

Below is a brief summary of the dissertation: 

Cancer treatments have improved greatly, yet patients still respond very differently to the same medication. This is partly because drugs are absorbed and processed differently from person to person. My research focuses on how we can better tailor cancer treatments to each individual patient, with the goal of improving effectiveness while reducing side effects.

A major part of this work examines patients with cancer that has spread to the lining of the abdomen (the peritoneum), particularly in stomach and colorectal cancer. These metastases are difficult to treat because standard chemotherapy given through the bloodstream hardly reaches the abdominal cavity. I therefore studied whether delivering chemotherapy directly into the abdomen can offer better results. My studies show that this local approach is safe, leads to much higher drug concentrations at the tumor site, and may improve survival. We also developed a national protocol to better diagnose these metastases, helping doctors choose the right treatment at the right time.

The second part of my research focuses on personalizing the dose of modern oral targeted therapies. Because patients metabolize these drugs differently, some receive too little—making the treatment less effective—while others receive too much and develop unnecessary side effects. Using Therapeutic Drug Monitoring (TDM), where drug levels in the blood are measured to adjust the dose, we explored which medications benefit from this approach and how other drugs may interact with cancer treatments. We also studied how certain medications can be safely “boosted” to reduce the required dose.

Overall, my research shows that personalized dosing and drug delivery are key to improving cancer care.