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Clinical Research

Reversal of PSA progression on abiraterone acetate through the administration with food in men with metastatic castration-resistant prostate cancer

Abstract

Background:

Owing to efficacy and tolerability, abiraterone acetate (AA) is a leading treatment for men with metastatic castration-resistant prostate cancer. Increased serum concentrations of AA, such as by taking AA with food, may lead to the inhibition of additional enzymes in the androgen synthesis pathway implicated in castration-resistant prostate cancer progression.

Methods:

Medical records of men with metastatic castration-resistant prostate cancer (mCRPC) who received AA between 1 April 2011 and 31 December 2013 were retrospectively reviewed. The primary outcome was the percent of men with a rising PSA on AA who experienced any PSA decline within 3 months after changing the administration of AA from without food to with food. Secondary outcomes were median time on AA therapy in men who received AA therapy without food versus those that switched administration from without food to with food at PSA progression, and the percent of men who experienced any decline in serum testosterone concentration, and the rate of adverse events observed while taking AA with food.

Results:

Nineteen men who switched AA administration from without food to with food and 41 patients who administered AA without food only were included in the study. Of those patients who took AA with food at PSA progression, a PSA decline was observed in 3 of the 19 (16%) men, including 3 of the 14 men who had an initial response to AA (21%). Testosterone declined in five out of seven patients from pre-food levels. The median time on AA therapy was increased by nearly 100 days in patients who switched AA administration from without food to with food. No increases in toxicity were observed.

Conclusion:

Some men with mCRPC may benefit from taking AA with food. Further prospective comparative studies are needed to determine if changing AA administration is beneficial.

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References

  1. Siegel R, Ma J, Zou Z, Jemal A . Cancer Statistics, 2014. CA Cancer J Clin 2014; 64: 9–24.

    Article  Google Scholar 

  2. Culig Z . Role of androgen receptor axis in prostate cancer. Urology 2003; 62: 21–26.

    Article  Google Scholar 

  3. Scher HI, Sawyers CL . Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen receptor signaling axis. J Clin Oncol 2005; 23: 8253–8261.

    Article  CAS  Google Scholar 

  4. Attard G, Reid AHM, Yap TA, Raynard F, Dowsett M, Settatree S et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration resistant prostate cancer commonly remains hormone driven. J Clin Oncol 2008; 26: 4563–4571.

    Article  CAS  Google Scholar 

  5. Massard C, Fizazi K . Targeting continued androgen receptor signaling in prostate cancer. Clin Cancer Res 2011; 17: 3876–3883.

    Article  CAS  Google Scholar 

  6. Ware KE, Garcia-Blanco MA, Armstrong AJ, Dehm SM . Biologic and clinical significance of androgen receptor variants in castration resistant prostate cancer. Endo Rel Cancer 2014; 21: T87–T103.

    Article  CAS  Google Scholar 

  7. Chang KH, Li R, Kuri B, Lotan Y, Roehrbom CG, Liu J et al. A gain-of-function mutation in DHT synthesis in castration-resistant prostate cancer. Cell 2013; 154: 1–11.

    Article  Google Scholar 

  8. O’Donnell A, Judson I, Dowsett M, Raynard F, Dearnaley D, Mason M et al. Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer 2004; 90: 2317–2325.

    Article  Google Scholar 

  9. Danila DC, Morris MJ, de Bono JS, Ryan CJ, Denmeade SR, Smith MR et al. Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration resistant prostate cancer. J Clin Oncol 2010; 28: 1496–1501.

    Article  CAS  Google Scholar 

  10. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011; 364: 1995–2005.

    Article  CAS  Google Scholar 

  11. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013; 368: 138–148.

    Article  CAS  Google Scholar 

  12. Helen Diller Family Comprehensive Cancer Center; University of California, San Francisco A phase II study of increased dose abiraterone acetate in patients with castration resistant prostate cancer. In: ClinicalTrials.gov. US National Library of Medicine: Bethesda, MD, 2000; [NCT01637402].

  13. Szmulewitz R ; University of Chicago Food effect study of abiraterone acetate for treatment of patients with castration resistant prostate cancer. In: ClinicalTrials.gov. US National Library of Medicine: Bethesda, MD, 2000; [NCT01543776].

    Google Scholar 

  14. Li R, Evaul K, Sharma K, Chang KH, Yoshimoto J, Liu J et al. Abiraterone inhibits 3β-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration resistant prostate cancer. Clin Cancer Res 2012; 18: 3571–3579.

    Article  CAS  Google Scholar 

  15. Ryan CJ, Shah S, Efstathiou E, Smith MR, Taplin ME, Bubley GJ et al. Phase II study of abiraterone acetate in chemotherapy-naïve metastatic castration-resistant prostate cancer displaying bone flare discordant with serologic response. Clin Cancer Res 2011; 17: 4854–4861.

    Article  CAS  Google Scholar 

  16. Ryan CJ, Smith MR, Fong L, Rosenberg JE, Kantoff P, Raynaud F et al. Phase 1 clinical trial of CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J Clin Oncol 2010; 28: 1481–1488.

    Article  CAS  Google Scholar 

  17. Noonan KL, North S, Bitting RL, Armstrong AJ, Ellard SL, Chi KN . Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progression after enzalutamide. Ann Oncol 2013; 24: 1802–1807.

    Article  CAS  Google Scholar 

  18. Loriot Y, Bianchini D, Ileana E, Sandhu S, Patrikidou A, Pexaro C et al. Antitumor activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Ann Oncol 2013; 24: 1807–1812.

    Article  CAS  Google Scholar 

  19. Suzman DL, Luber D, Schweizer MT, Antonarakis ES . Clinical activity of enzalutamide versus docetaxel in men with castration-resistant prostate cancer progressing after abiraterone. Prostate 2014; 74: 1278–1285.

    Article  CAS  Google Scholar 

  20. Bianchini D, Lorente D, Rodriguez-Vida A, Omlin A, Pezaro C, Ferraldeschi R et al. Antitumor activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone. Eur J Cancer 2014; 50: 78–84.

    Article  CAS  Google Scholar 

  21. Schrader AJ, Boegemann M, Ohlmann CH, Schnoeller TJ, Krabbe LM, Hajili T et al. Enzalutamide in castration-resistant prostate cancer patients progressing after docetaxel and abiraterone. Eur Urol 2014; 65: 30–36.

    Article  CAS  Google Scholar 

  22. Ghani S, Attwood K, Elefante A, Khalid K, Trump D . Evaluation of prostate specific antigen (PSA) response following abiraterone in metastatic, castration resistant prostate cancer (mCRPC) previously treated with ketoconazole compared to ketoconazole naïve patients: a retrospective review. J Clin Oncol 2014 ASCO Meeting Abstracts; 32, suppl (abstract e16067).

  23. Kim W, Wilton J, Li Z, Fong L, Friedlander TW, Hsieh AC et al. Activity of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) patients previously treated with ketoconazole: a prospective phase II study from the Prostate Cancer Clinical Trials Consortium. J Clin Oncol 2014; ASCO Meeting Abstracts 32, suppl: 4 (abstract 5039).

  24. Zhao B, Garcia JA, Gilligan TD, Rini BI, Drecicer R . Clinical activity of abiraterone acetate in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J Clin Oncol 2014; 32, suppl: 4 (abstract 5039).

  25. Enzalutamide (Xtandi® Prescribing Information. Catalent Pharma Solutions, LLC, 2012.

  26. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014; 371: 1028–1038.

    Article  Google Scholar 

  27. Leibowitz-Amit R, Atenafu EG, Seah J, Templeton AJ, Vera-Badillo FE, Alimohamed NS et al. Low-dose abiraterone with food in men with metastatic castration-resistant prostate cancer (mCRPC): The Princess Margaret Cancer Center experience. J Clin Oncol 2014 ASCO Meeting Abstracts; 32, suppl: 5 (abstract 5077).

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Acknowledgements

We thank John Pura, MPH and Maragatha Kuchibhatla, PhD for statistical support and Ceci Chamorro for database management. No funding was obtained for this research.

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Correspondence to A J Armstrong.

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Competing interests

AJA receives research support, serves on the advisory board, and is a consultant for Janssen Pharmaceutica, the manufacturer of abiraterone acetate. MRH receives research support from Janssen Pharmaceutica. JTS, RAM and KD declare no conflicts of interest.

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Stover, J., Moore, R., Davis, K. et al. Reversal of PSA progression on abiraterone acetate through the administration with food in men with metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 18, 161–166 (2015). https://doi.org/10.1038/pcan.2015.7

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