@article{dd5ba80399de4386b37be5d7e55c8b1c,
title = "Concomitant intake of abiraterone acetate and food to increase pharmacokinetic exposure: real life data from a therapeutic drug monitoring programme",
abstract = "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. 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. ",
keywords = "abiraterone acetate, drug monitoring, pharmacokinetics, prostate cancer",
author = "Groenland, {Stefanie L} and {van Nuland}, Merel and Bergman, {Andries M} and {de Feijter}, {Jeantine M} and Dezentje, {Vincent O} and Hilde Rosing and Beijnen, {Jos H} and Huitema, {Alwin D R} and Neeltje Steeghs",
note = "Funding Information: The authors would like to thank all patients for their participation in this study. This work was supported by unrestricted research grants from Novartis , Pfizer and Roche . The funding sources had no involvement in the study design, collection, analysis and interpretation of data, the writing of the report or in the decision to submit the article for publication. This work was presented in part at the 2019 ASCO (American Society of Clinical Oncology) Annual Meeting, Chicago (J Clin Oncol 37, 2019 (suppl; abstr 3117)). Funding Information: This study was supported by unrestricted research grants from Novartis , Pfizer and Roche . They had no role in the design of the study, the collection, analysis, and interpretation of the data, nor did they have any further roles in the analyses and reporting of the results. Funding Information: This study was supported by unrestricted research grants from Novartis, Pfizer and Roche. They had no role in the design of the study, the collection, analysis, and interpretation of the data, nor did they have any further roles in the analyses and reporting of the results.A.M.B. received research grants for the institute from Sanofi, Bayer and Astellas (outside the submitted work). J.H.B. received research grants for the institute from Astex, PharmaMar and Roche (outside the submitted work) and is a part-time employee, stock holder and patent holder of Modra Pharmaceuticals (a spin-out company developing oral taxane formulations, not related to this study). The other authors declare no conflict of interest.The authors would like to thank all patients for their participation in this study. This work was supported by unrestricted research grants from Novartis, Pfizer and Roche. The funding sources had no involvement in the study design, collection, analysis and interpretation of data, the writing of the report or in the decision to submit the article for publication. This work was presented in part at the 2019 ASCO (American Society of Clinical Oncology) Annual Meeting, Chicago (J Clin Oncol 37, 2019 (suppl; abstr 3117)). Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",
year = "2020",
month = may,
doi = "10.1016/j.ejca.2020.02.012",
language = "English",
volume = "130",
pages = "32--38",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Limited",
}