The therapeutic use of some drugs could be optimized by an individualization of their dosage regimen, based on blood or plasma circulating concentrations measurement in patients thanks to the therapeutic drug monitoring (TDM) feedback strategy. The modern oral targeted anti- cancer drugs are directed against cancer-specific molecules and signaling pathways and seems to be characterized by impressive efficacy and limited non-specific toxicities. Nevertheless, drug resistance, persistence of cancer stem cells, and adverse drug effects still limit their ability to stabilize or cure malignant diseases in the long term.
Oral anticancer drugs are generally licensed for use at fixed doses even though most of them would meet almost all criteria for successful TDM implementation in clinical practice: long-term and continuous therapy, availability of appropriate bioanalytical methods for quantification in clinical samples, high inter-individual pharmacokinetic variability (because of variations in metabolism, protein binding, etc.) but limited intra-individual pharmacokinetic variability, alongside consistent associations between concentration and response. They have also the poten- tial to be involved in multiple interactions (drug–drug; drug–food) and exhibit adherence issues with lifelong treatment. Imatinib was the first to benefit from prospective randomized controlled trial to assess the clinical benefit of a TDM approach, however with contrasting results. Progresses in TDM are still needed, especially for new targeted anticancer agents, both on a conceptual and a practical level. Advances toward modern TDM approaches are ongoing in the field of oncology and other therapeutic area: development of appropriate pharmacokinetic and pharmacokinetic/pharmacodynamic models and improvement of meta-analysis methods to aggregate them, validation of therapeutic target in randomized controlled trials, elaboration of conceptual and practical framework for practitioners and conduct of technological efforts toward miniaturization and development of computer software to assist them.