PhD defence S. (Sabine) Visser

Dissertation in short:

Although precision medicine, or “tailored therapy”, has become a primary goal in cancer care, this is still largely uncharted territory for chemotherapy in general. This also holds true for pemetrexed, a frequently used chemotherapeutic agent in the treatment of non-small-cell lung cancer. It is unknown why this therapy only is beneficial in a subgroup of patients, why some patients experience serious negative side effects and how patients value their own treatment. In this thesis, we have observed that renal impairment due to pemetrexed maintenance treatment is common and also jeopardize further treatment, as they frequently lead to chronic kidney disease and treatment withdrawal. Greater awareness should be present in patients who have a decreased renal function before start of treatment and/or in patients whose renal function rapidly declines during the first courses of chemotherapy. Furthermore, strong indications were found that the incidence of severe side effects of pemetrexed could be reduced if we change our current dosing strategy, based on body surface area, to other dosing strategies like renal function-based or fixed-dose with a lower fixed-dose for patients with a decreased renal function. Additionally, we have discovered a number of new genetic abnormalities within the patient and the tumor which could play a role in driving tumor resistance and the occurrence of side effects. At last, we have shown that patients are satisfied with their treatment with pemetrexed, even if they experience side effects and/or decrease in quality of life. Importantly, attention should be payed to mild side effects (alongside of severe side effects), for they may negatively influence quality of life.