Towards Rational Cancer Therapeutics: Optimizing Dosing, Delivery, Scheduling, and Combinations.

The current trend to personalize anticancer therapies mostly relies on selecting the best drug or combination of drugs to achieve optimal efficacy in patients. In addition to the comprehensive genetic and molecular knowledge of each tumor before choosing the drugs to be given, there is probably much room left for improvement by further personalizing the very modes by which the drugs are given, once they have been carefully selected. In particular, shifting from standard dosing to tailored dosing should help in maintaining drug exposure levels in the right therapeutic window, thus ensuring that the efficacy/toxicity balance is optimal. This paper covers the current knowledge regarding pharmacokinetic/pharmacodynamic relationships of anticancer agents, from decades-old cytotoxics to the latest immune checkpoint inhibitors, the most frequent sources for long-neglected interpatient variability impacting on drug exposure levels, and what could be done to achieve real personalized medicine in oncology such as implementing therapeutic drug monitoring with adaptive dosing strategies or using model-driven modalities for personalized dosing and scheduling.