Optimizing Treatment with Tyrosine Kinase Inhibitors: Focus on Dosing Schedules

The integration in cancer therapy of tyrosine kinase inhibitors (TKIs), drugs that, by binding on specific enzymes, block the activation of basic survival cellular pathways, has led to significant beneficial effects for the patients.  Simultaneously these drugs have fallen short of the initial high expectations since their use is limited by their significant toxicity profile and the development of resistance to therapy.  

Could thinking outside the box in regards to the way these agents are dosed, provide a new, more efficient equilibrium between toxicity and efficacy?  

In this session, we will be focusing on one of the TKIs, namely sunitinib, to present a proof of principle that modulation of the dosing scheduling could potentially broaden the therapeutic window.  The whole trajectory, from preclinical work to clinical application is presented; initially the effect of this alternative dosing schedule observed in vitro on cancer cells, followed by the effect in vivo on tumors growing on the chorioallantoic membrane (CAM) of the chicken embryo and finally the bedside translation of these preclinical data in the context of a (phase I ) clinical trial. The results, regarding the observed side effects and preliminary efficacy data of patients with advanced cancer treated  with this alternative scheduling will be presented.