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

Abstract

RESULTS

In total, 32 evaluable patients were included, of which 20 patients (63%) had a C_min < 8.4 ng/mL at a certain time point during treatment. These patients were recommended to take abiraterone acetate concomitantly with food, after which C_min 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%).

CONCLUSION

Therapeutic drug monitoring of abiraterone was applied in clinical practice and proved to be feasible. Concomitant intake with food resulted in a significant increase in C_min and offers a cost-neutral opportunity to optimise exposure in patients with low C_min.

AIM

Abiraterone 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 (C_min) ≥ 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.

METHODS

Patients 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 C_min < 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.