Biomarkers for individualizing platinum-based therapy of patients with non-small cell lung cancer

Abstract

In the Netherlands, more than 14,000 patients are diagnosed with lung cancer each year. Despite the rapid introduction of therapeutic innovations, platinum-based therapy, consisting of cisplatin of carboplatin, remains a cornerstone of lung cancer treatment. However, platinum-based therapy is often accompanied by dose-limiting and severe toxicities, such as disturbance of blood values (haematological toxicities), nephro- and neurotoxicity. Frequently, severe toxicities necessitate dose reduction, treatment delay or even early treatment termination, which can affect treatment response and, thus, disease prognosis. Some patients seem to be more susceptible to developing disabling side effects. However, identifying those patients with the highest risk of developing toxicity is hardly possible and therefore there is a need for predictors (biomarkers) for toxicity.

This thesis aims to provide novel insights into the association between biomarkers and platinum-based therapy-related response and toxicity in patients with lung cancer. From the results of the studies it can be concluded that genetic predisposition due to genetic variants in specific genes (i.e., BACH2, TRPV1 variants) may be important in the occurrence of nephro- and neurotoxicity. Furthermore, it was found that patients with low skeletal muscle mass have a significantly higher risk of developing severe haematological toxicity. In addition, (changes in) certain blood values (CEA, LDH) may serve as valuable biomarkers to determine treatment response of radiological response and overall survival.

In conclusion, this thesis provides novel insights into biomarkers for platinum-based therapy-related response and toxicity. These results encourage an individualized approach and contribute to optimizing platinum-based therapy in patients with lung cancer.