Abstract

PREDICTIVE PHARMACOGENETIC AND PHARMACOKINETIC MARKERS OF IRINOTECAN-INDUCED TOXICITY PAVING THE WAY FOR A PERSONALIZED CANCER THERAPY: A REVIEW OF LITERATURE

Aoullay Z.*, Lejmi H., El Bouchikhi I., Meddah B., Cherrah Y.

ABSTRACT

There is great inter-individual variability in terms of toxicities and response for patients treated with different anticancer molecules. Thus, the real challenge in cancer chemotherapy remains prediction of patient populations at risk of treatment failure and/or prone to high risk of toxicity. Pharmacogenetics can be used to help predict these outcomes. Irinotecan is a chemotherapeutic agent that is subject to the most pharmacogenetic studies since the therapeutic index or the ratio between efficacy and tolerance of therapy is generally very narrow, and is therefore, more sensitive to metabolic variations. In this review, we discussed both pharmacokinetic and pharmacogenetic approches to predict irinotecan tolerability, drawing attention to the fact that improvement of therapeutic index involves taking into account both the intrinsic genetic characteristics of the patients’ metabolism (pharmacogenetics) and the optimization of the effective doses to administer based on studying the fate of the drug in the body of each patient (pharmacokinetics). We can conclude from the present review that combined pharmacokinetic and pharmacogenetic approach is a better alternative to overcome all the issues previously mentioned, leading to an efficient personalized dose adjustment.

Keywords: Irinotecan, toxicity, pharmacokinetics, pharmacogenetics, biomarkers, personalized medicine.