Concomitant intake of abiraterone acetate and food to increase pharmacokinetic exposure: real life data from a therapeutic drug monitoring programme

Abstract

AimAbiraterone acetate is approved for the treatment of metastatic prostate cancer. At the currently used fixed dose of 1000 mg once daily in modified fasting state, 40% of patients do not reach the efficacy threshold of a minimum plasma concentration (Cmin) ≥ 8.4 ng/mL and are thereby at risk of decreased treatment efficacy. This study aims to evaluate whether pharmacokinetically (PK) guided abiraterone acetate dosing with a food intervention is feasible and results in an increased percentage of patients with concentrations above the target. MethodsPatients starting regular treatment with abiraterone acetate in modified fasting state were included. Pharmacokinetic analysis was performed 4, 8 and 12 weeks after start of treatment and every 12 weeks thereafter. In case of Cmin < 8.4 ng/mL and acceptable toxicity, a PK-guided intervention was recommended. The first step was concomitant intake of abiraterone acetate with a light meal or a snack. ResultsIn total, 32 evaluable patients were included, of which 20 patients (63%) had a Cmin < 8.4 ng/mL at a certain time point during treatment. These patients were recommended to take abiraterone acetate concomitantly with food, after which Cmin increased from 6.9 ng/mL to 27 ng/mL (p < 0.001) without additional toxicities. This intervention led to adequate exposure in 28 patients (87.5%). ConclusionTherapeutic drug monitoring of abiraterone was applied in clinical practice and proved to be feasible. Concomitant intake with food resulted in a significant increase in Cmin and offers a cost-neutral opportunity to optimise exposure in patients with low Cmin.