Personalized therapy for oral anticancer drugs: an integrated approach based on therapeutic drug monitoring and pharmacogenetics for sunitinib and imatinib

Oral anticancer drugs have substantially enhanced treatment options for patients with cancer: from the use of cytotoxic drugs and non-specific chemotherapy to chronic oral treatment with targeted molecular therapies. However, these drugs are administered at fixed dose, causing high interpatients variability in pharmacokinetics (PK). As results, patients show wide differences in drug exposure and thus in treatment outcomes (efficacy/toxicity). This study uses therapeutic drug monitoring (TDM) approach to reduce this variability in patients administered with imatinib and sunitinib: blood samples are prospectively collected within an active pharmacovigilance protocol at pharmacology unit of Centro di Riferimento Oncologico, and samples are analyzed to quantify drug’s concentrations and monitor patient’s drug exposure. Pharmacogenetics (PGx) is integrated with TDM to further reduce interpatients variability describing patients from the genetic point of view. Particularly, a panel of SNPs involving genes of drugs metabolism have been analyzed with the aim to correlate the patient genetic profile to drug exposure. Finally, both TDM and PGx results are integrated into a pharmacological advice that physicians can refer to in order to personalize these oral anticancer therapies.