42 Poster Discussion - Tumor drug exposure is positively correlated with an improved outcome, in patients with advanced solid tumors, upon treatment with a high dose intermittent sunitinib regimen

Abstract

Background: Innovative strategies for the clinical use of multitargeting tyrosine kinase inhibitors (TKIs), like sunitinib, are needed to fully exploit their antitumor activity. The inhibitory activity of these drugs depends on the tumor drug concentration, its affinity for kinases and kinase activity in tumor cells. Their broader inhibitory capacity at high concentrations might be essential for optimal suppression of tumor growth and induction of apoptosis. In a recent phase I trial NCT02058901, we administered high dose intermittent sunitinib 300 mg once a week and 700 mg once every two weeks, to patients with advanced tumors. This strategy resulted in higher peak plasma concentrations compared to regular dosing of sunitinib, without drug accumulation and with promising clinical benefit. We hypothesized that these plasma concentrations subsequently lead to higher tumor drug concentrations. Here, we determined tumor- and skin tissue drug concentrations of patients participating in this trial and related them to the plasma concentrations and clinical outcome.