Long-Term Pharmacokinetic Follow-Up of Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jun 19

PMID 38892246

Authors

Emmanuel Chamorey

Marc Pujalte-Martin

Jean-Marc Ferrero

Hakim Mahammedi

Gwenaelle Gravis

Guilhem Roubaud

Philippe Beuzeboc

Remy Largillier

Delphine Borchiellini

Claude Linassier

Helene Bouges

Marie-Christine Etienne-Grimaldi

Renaud Schiappa

Jocelyn Gal

Gerard Milano

Affiliations

Soon will be listed here.

Abstract

This ABIGENE pharmacokinetic (PK) study sought mainly to characterize the unchanged drug PK during long-term abiraterone acetate (AA) administration in advanced prostate cancer patients (81 patients). It was observed that individual AA concentrations remained constant over treatment time, with no noticeable changes during repeated long-term drug administration for up to 120 days. There was no correlation between AA concentrations and survival outcomes. However, a significant association between higher AA concentrations and better clinical benefit was observed ( = 0.041). The safety data did not correlate with the AA PK data. A significant positive correlation (r = 0.40, < 0.001) was observed between mean AA concentration and patient age: the older the patient, the higher the AA concentration. Patient age was found to impact steady-state AA concentration: the older the patient, the higher the mean AA concentration. Altogether, these data may help to guide future research and clinical trials in order to maximize the benefits of AA metastatic castration-resistant prostate cancer patients.

References

Crombag M, van Nuland M, Bergman A, Rosing H, Schellens J, Huitema A . Impact of age on exposure to oral antiandrogen therapies in clinical practice. Prostate Cancer Prostatic Dis. 2018; 22(1):168-175. DOI: 10.1038/s41391-018-0096-z. View

Fallah J, Xu J, Weinstock C, Brave M, Bloomquist E, Fiero M . FDA Approval Summary: Olaparib in Combination With Abiraterone for Treatment of Patients With -Mutated Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023; 42(5):605-613. DOI: 10.1200/JCO.23.01868. View

Nkeck J, Ida C, Koe V, Ndam A, Jessica Y, Manuella E . Gamma glutamyl transferases in association with cardiovascular risk scores in non-diabetic hypertensive Cameroonians: preliminary data from HYRICCA study. BMC Res Notes. 2022; 15(1):300. PMC: 9479233. DOI: 10.1186/s13104-022-06190-1. View

Stuyckens K, Saad F, Xu X, Ryan C, Smith M, Griffin T . Population pharmacokinetic analysis of abiraterone in chemotherapy-naïve and docetaxel-treated patients with metastatic castration-resistant prostate cancer. Clin Pharmacokinet. 2014; 53(12):1149-60. DOI: 10.1007/s40262-014-0178-6. View

Blanchet B, Carton E, Alyamani M, Golmard L, Huillard O, Thomas-Scheomann A . A PK/PD study of Delta-4 abiraterone metabolite in metastatic castration-resistant prostate cancer patients. Pharmacol Res. 2018; 136:56-61. DOI: 10.1016/j.phrs.2018.08.016. View

Benoist G, van der Meulen E, Lubberman F, Gerritsen W, Smilde T, Schalken J . Analytical challenges in quantifying abiraterone with LC-MS/MS in human plasma. Biomed Chromatogr. 2017; 31(11). PMC: 6114173. DOI: 10.1002/bmc.3986. View

de Bono J, Logothetis C, Molina A, Fizazi K, North S, Chu L . Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011; 364(21):1995-2005. PMC: 3471149. DOI: 10.1056/NEJMoa1014618. View

Stillhart C, Asteriadis A, Bocharova E, Eksteen G, Harder F, Kusch J . The impact of advanced age on gastrointestinal characteristics that are relevant to oral drug absorption: An AGePOP review. Eur J Pharm Sci. 2023; 187:106452. DOI: 10.1016/j.ejps.2023.106452. View

Mangoni A, Jackson S . Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2003; 57(1):6-14. PMC: 1884408. DOI: 10.1046/j.1365-2125.2003.02007.x. View

10.

Scher H, Halabi S, Tannock I, Morris M, Sternberg C, Carducci M . Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008; 26(7):1148-59. PMC: 4010133. DOI: 10.1200/JCO.2007.12.4487. View

11.

ODonnell A, Judson I, Dowsett M, Raynaud F, Dearnaley D, Mason M . Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer. 2004; 90(12):2317-25. PMC: 2409523. DOI: 10.1038/sj.bjc.6601879. View

12.

Logothetis C, Basch E, Molina A, Fizazi K, North S, Chi K . Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301.... Lancet Oncol. 2012; 13(12):1210-7. DOI: 10.1016/S1470-2045(12)70473-4. View

13.

Mulders P, Molina A, Marberger M, Saad F, Higano C, Chi K . Efficacy and safety of abiraterone acetate in an elderly patient subgroup (aged 75 and older) with metastatic castration-resistant prostate cancer after docetaxel-based chemotherapy. Eur Urol. 2013; 65(5):875-83. DOI: 10.1016/j.eururo.2013.09.005. View

14.

Ferrero J, Mahammedi H, Gravis G, Roubaud G, Beuzeboc P, Largillier R . Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer. Pharmaceutics. 2023; 15(2). PMC: 9959353. DOI: 10.3390/pharmaceutics15020651. View

15.

Franzini M, Scataglini I, Ricchiuti A, Fierabracci V, Paolicchi A, Pompella A . Association between plasma gamma-glutamyltransferase fractions and metabolic syndrome among hypertensive patients. Sci Rep. 2017; 7(1):12003. PMC: 5607275. DOI: 10.1038/s41598-017-12356-w. View

16.

Narendra G, Choudhary S, Raju B, Verma H, Silakari O . Role of Genetic Polymorphisms in Drug-Metabolizing Enzyme-Mediated Toxicity and Pharmacokinetic Resistance to Anti-Cancer Agents: A Review on the Pharmacogenomics Aspect. Clin Pharmacokinet. 2022; 61(11):1495-1517. DOI: 10.1007/s40262-022-01174-7. View

17.

Carton E, Noe G, Huillard O, Golmard L, Giroux J, Cessot A . Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients. Eur J Cancer. 2016; 72:54-61. DOI: 10.1016/j.ejca.2016.11.027. View

18.

Boerrigter E, Benoist G, Overbeek J, Donders R, Mehra N, van Oort I . The effect of chemotherapy on the exposure-response relation of abiraterone in metastatic castration-resistant prostate cancer. Br J Clin Pharmacol. 2021; 88(3):1170-1178. PMC: 9293353. DOI: 10.1111/bcp.15057. View

19.

Verma H, Bahia M, Choudhary S, Singh P, Silakari O . Drug metabolizing enzymes-associated chemo resistance and strategies to overcome it. Drug Metab Rev. 2019; 51(2):196-223. DOI: 10.1080/03602532.2019.1632886. View

20.

Caffo O, Maines F, Rizzo M, Kinspergher S, Veccia A . Metastatic castration-resistant prostate cancer in very elderly patients: challenges and solutions. Clin Interv Aging. 2017; 12:19-28. PMC: 5192056. DOI: 10.2147/CIA.S98143. View