Les enjeux de l'observance pour les nouvelles chimiothérapies par voie orale : intérêt du modèle pharmacocinétique-pharmacodynamique

Nowadays, more and more oral anticancer chemotherapies are developed either for cytotoxic or new targeted drugs. But this relatively new route of administration in oncology drives to new problems in treatment management and particularly to non-compliance, i.e. the deviance of the actual way patients take their treatment with the prescription. Population PK-PD models and Monte-Carlo simulations allow to study the impact of non-compliance on toxicities. After a brief review on recent developments about oral chemotherapies, this work presents a simulation where non-compliance, modelled with a two state Markov chain defining four compliance profiles from excellent to poor, is linked to two dose-toxicity (continuous or categorical) population models. Simulated patients with the lowest compliance level were less exposed to treatment and therefore experienced less toxicity with shorter events. Nevertheless treatment efficacy is also lower, and this loss of efficacy may compromise patient's outcome. These results foresee the necessity of global simulations, combining compliance, toxicity and efficacy modelling.