Correlation Between Trough Level of Abiraterone and Prostate-Specific Antigen (PSA) Response in Metastatic Hormone-Sensitive Prostate Cancer

Overview

Journal Med Sci Monit

Specialties General Medicine
Pathology

Date 2022 Oct 14

PMID 36229939

Authors

Zin W Myint

Jill M Kolesar

Joseph Robert McCorkle

Jianrong Wu

Carleton S Ellis

Danielle E Otto

Peng Wang

Affiliations

Soon will be listed here.

Abstract

BACKGROUND Prostate cancer growth is primarily driven by testosterone and 5a-dihydrotestosterone. Abiraterone is an irreversible inhibitor of CYP17, and CYP17 inhibition is a required step in testosterone biosynthesis. Previous studies have shown that abiraterone trough levels are predictive of prostate-specific antigen (PSA) response in metastatic castrate-resistant prostate cancer (mCRPC). It has not been demonstrated if this association exists for patients with metastatic hormone-sensitive prostate cancer (mHSPC). In this study, we aimed to explore the correlation and association between abiraterone trough levels and PSA levels in patients with mHSPC. MATERIAL AND METHODS This was a single-center, prospective, observational study of patients with mHSPC being treated with abiraterone acetate (AA) 1000 mg once daily. Abiraterone trough levels (22-26 h after drug administration) were drawn at 1, 3, and 7 months after treatment initiation. RESULTS Thirteen patients with mHSPC were enrolled, and complete pharmacokinetic data were available for 8 patients. The mean trough levels at 1 month, 3 months, and 7 months were 34.49 ng/mL (3.36-240.46), 13.82 ng/mL (2.91-29.96), and 15.7 ng/mL (3.58-26.86), respectively. The correlation between the 1-month abiraterone trough level and 1-month PSA level was 0.29 (P=0.38), between 3-month abiraterone trough and 3-month PSA was -0.61 (P=0.08), and between 7-month abiraterone trough and 7-month PSA was -0.31 (P=0.54). CONCLUSIONS This study demonstrated a trend toward a negative correlation between 3-month abiraterone trough levels and PSA levels, but the correlation was not statistically significant. A study with a larger prospective sample size is needed to validate these findings.

References

Ryan C, Smith M, de Bono J, Molina A, Logothetis C, de Souza P . Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2012; 368(2):138-48. PMC: 3683570. DOI: 10.1056/NEJMoa1209096. View

Alyamani M, Li Z, Upadhyay S, Anderson D, Auchus R, Sharifi N . Development and validation of a novel LC-MS/MS method for simultaneous determination of abiraterone and its seven steroidal metabolites in human serum: Innovation in separation of diastereoisomers without use of a chiral column. J Steroid Biochem Mol Biol. 2016; 172:231-239. PMC: 5124534. DOI: 10.1016/j.jsbmb.2016.04.002. View

Agarwal N, Hahn A, Gill D, Farnham J, Poole A, Cannon-Albright L . Independent Validation of Effect of HSD3B1 Genotype on Response to Androgen-Deprivation Therapy in Prostate Cancer. JAMA Oncol. 2017; 3(6):856-857. PMC: 5824318. DOI: 10.1001/jamaoncol.2017.0147. View

Aurilio G, Cimadamore A, Mazzucchelli R, Lopez-Beltran A, Verri E, Scarpelli M . Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications. Cells. 2020; 9(12). PMC: 7763510. DOI: 10.3390/cells9122653. View

Khalaf D, Aragon I, Annala M, Lozano R, Taavitsainen S, Lorente D . HSD3B1 (1245A>C) germline variant and clinical outcomes in metastatic castration-resistant prostate cancer patients treated with abiraterone and enzalutamide: results from two prospective studies. Ann Oncol. 2020; 31(9):1186-1197. DOI: 10.1016/j.annonc.2020.06.006. View

Chang K, Li R, Kuri B, Lotan Y, Roehrborn C, Liu J . A gain-of-function mutation in DHT synthesis in castration-resistant prostate cancer. Cell. 2013; 154(5):1074-1084. PMC: 3931012. DOI: 10.1016/j.cell.2013.07.029. View

Barrie S, Potter G, Goddard P, Haynes B, Dowsett M, Jarman M . Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase). J Steroid Biochem Mol Biol. 1994; 50(5-6):267-73. DOI: 10.1016/0960-0760(94)90131-7. View

Nakanishi S, Goya M, Tamaki M, Oshiro T, Saito S . Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer. BMC Res Notes. 2021; 14(1):227. PMC: 8176613. DOI: 10.1186/s13104-021-05641-5. View

Caffo O, Veccia A, Maines F, Bonetta A, Spizzo G, Galligioni E . Potential value of rapid prostate-specific antigen decline in identifying primary resistance to abiraterone acetate and enzalutamide. Future Oncol. 2014; 10(6):985-93. DOI: 10.2217/fon.14.24. View

10.

Altman N, Krzywinski M . Association, correlation and causation. Nat Methods. 2015; 12(10):899-900. DOI: 10.1038/nmeth.3587. View

11.

Hearn J, Sweeney C, Almassi N, Reichard C, Reddy C, Li H . HSD3B1 Genotype and Clinical Outcomes in Metastatic Castration-Sensitive Prostate Cancer. JAMA Oncol. 2020; 6(4):e196496. PMC: 7042830. DOI: 10.1001/jamaoncol.2019.6496. View

12.

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

13.

Almassi N, Reichard C, Li J, Russell C, Perry J, Ryan C . HSD3B1 and Response to a Nonsteroidal CYP17A1 Inhibitor in Castration-Resistant Prostate Cancer. JAMA Oncol. 2017; 4(4):554-557. PMC: 5933361. DOI: 10.1001/jamaoncol.2017.3159. View

14.

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

15.

Mei Z, Yang T, Liu Y, Gao Y, Hou Z, Zhuang Q . Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment. Cell Rep Med. 2022; 3(5):100608. PMC: 9133401. DOI: 10.1016/j.xcrm.2022.100608. View

16.

Boerrigter E, Benoist G, van Oort I, Verhaegh G, de Haan A, van Hooij O . RNA Biomarkers as a Response Measure for Survival in Patients with Metastatic Castration-Resistant Prostate Cancer. Cancers (Basel). 2021; 13(24). PMC: 8699291. DOI: 10.3390/cancers13246279. View

17.

Stein C, Levin R, Given R, Higano C, Nemeth P, Bosch B . Randomized phase 2 therapeutic equivalence study of abiraterone acetate fine particle formulation vs. originator abiraterone acetate in patients with metastatic castration-resistant prostate cancer: The STAAR study. Urol Oncol. 2017; 36(2):81.e9-81.e16. DOI: 10.1016/j.urolonc.2017.10.018. View

18.

Buttigliero C, Tucci M, Bertaglia V, Vignani F, Bironzo P, Di Maio M . Understanding and overcoming the mechanisms of primary and acquired resistance to abiraterone and enzalutamide in castration resistant prostate cancer. Cancer Treat Rev. 2015; 41(10):884-92. DOI: 10.1016/j.ctrv.2015.08.002. View

19.

Antonarakis E, Lu C, Wang H, Luber B, Nakazawa M, Roeser J . AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014; 371(11):1028-38. PMC: 4201502. DOI: 10.1056/NEJMoa1315815. View

20.

Sweeney C, Chen Y, Carducci M, Liu G, Jarrard D, Eisenberger M . Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015; 373(8):737-46. PMC: 4562797. DOI: 10.1056/NEJMoa1503747. View