In this study, the drug capecitabine is investigated. Capecitabine is commonly used to treat breast, colon, and stomach cancers. Capecitabine is taken in tablet form. In the body, capecitabine is converted into the active molecule that has anti-cancer effects. This molecule is called 5-FU. The transformation of capecitabine to 5-FU occurs through specific proteins in the liver, also known as enzymes.

Unfortunately, capecitabine can also cause side effects. One of the most common side effects is hand-foot syndrome. In hand-foot syndrome, the palms of the hands and soles of the feet become red and painful. Previous research has shown that patients in whom one of the enzymes responsible for converting capecitabine in the liver does not function properly experience an increase in side effects frequency, particularly severe hand-foot syndrome. This specific enzyme is called CES1. It is believed that side effects occur more frequently because capecitabine is transformed more slowly, eventually leading to a prolonged exposure to 5-FU in the body.

In roughly one in three people, this enzyme functions less efficiently. To gain a better understanding of how this mechanism works, we aim to conduct this study. In this study, we will examine if patients with a less effective CES1 enzyme have higher amounts of 5-FU in their blood. We will also look into whether these patients develop side effects, such as hand-foot syndrome, more frequently. This information could eventually help us develop new strategies to reduce side effects for these patients in the future.

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

• 18 years of age or older;
• Planned to start treatment with concomitant capecitabine and oxaliplatin according to standard of care (irrespective of dose);
• Fit for treatment with capecitabine and oxaliplatin as judged by the treating physician;
• Capable of understanding and complying with protocol requirements and able to understand and sign the informed consent form.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

• Carrier of a known clinically relevant DPYD variant (i.e. *2A, *7, *13, c.1236G>A or c.2846A>T);
• Any medical condition that is known to influence capecitabine absorption (i.e. a Roux-en-Y gastric bypass operation or complete gastric resection; an esophagectomy is not considered to impair absorption);
• Prior treatment with fluoropyrimidines;
• Use of DPD-inhibitors and/or allopurinol;
• Known pregnancy at baseline.

Patients with cancer who are intended to start with CAPOX treatment.