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`Letters to the Editor
`
`Is Dexamethasone a Better Partner for
`
`Abiraterone Than Prednisolone?
`
`I read with great interest the article by Auchus et al. [1] in which
`they comprehensively reviewed the use of prednisone with
`abiraterone acetate in the treatment of metastatic castration-
`resistant prostate cancer (CRPC). Although prednisolone is the
`most commonly used corticosteroid with abiraterone in clinical
`trials and is the standard of care as recommended by current
`guidelines, two recent trials have shown better response rates
`and progression-free survival with dexamethasone compared
`with prednisolone. In the first trial, Lorente et al. [2] showed that
`durable prostate-specific antigen (PSA) responses might be
`achieved with a switch from prednisolone to dexamethasone
`(0.5 mg/day) in patients progressing on abiraterone. In patients
`with CRPC and progressive disease with abiraterone-prednisolone,
`11 of 30 patients (39%) had confirmed $30% PSA decline after
`switching to dexamethasone with median time to PSA progression
`of 11.7 weeks. These results are comparable with the response
`rate (41%) and duration (2.8 months) with enzalutamide after
`abiraterone in CRPC treatment [3].
`The second trial
`is a randomized phase 2 trial that
`compared the efficacy of prednisolone (5 mg b.i.d.) and
`dexamethasone (0.5 mg/day) in chemotherapy-na¨ıve patients
`with CRPC. In evaluable patients, the PSA response rates
`were 47% versus 24% for dexamethasone and prednisolone,
`respectively (p 5 .05). Median time to PSA progression was 9.7
`months on dexamethasone versus 5.1 months on prednisolone
`(hazard ratio, 1.6; 95% confidence interval, 0.9–2.8). Among
`patients who crossed over at PSA progression on prednisolone,
`37% had a confirmed PSA response to dexamethasone [4].
`Pharmacokinetic and pharmacodynamic differences between
`dexamethasone and prednisolone might partially explain this
`phenomenon. The half-life of dexamethasone is longer, which
`may result in more effective suppression of adrenocorticotro-
`pic hormone and more proficient antitumoral activity. Second,
`abiraterone inhibits CYP 3A4, decreases the clearance, and
`further increases the half-life of dexamethasone, whereas
`prednisolone is usually not affected [5]. On the other hand,
`
`differences in the activity of synthetic glucocorticoids at the
`glucocorticoid receptor level might also cause alterations in
`efficacy [6].
`In conclusion, dexamethasone may be a better partner
`for abiraterone compared with prednisolone. Upfront use
`of dexamethasone with abiraterone or a switch from pre-
`dnisolone to dexamethasone at PSA progression might
`be feasible options and are currently being tested in larger
`trials (ClinicalTrials.gov ID NCT01867710, Abiraterone With
`Different Steroid Regimens for Side Effect Related to
`Mineralcorticoid Excess Prevention in Prostate Cancer Prior
`to Chemotherapy).
`
`OMER DIZDAR
`
`Department of Preventive Oncology, Hacettepe University Cancer
`Institute, Sihhiye, Ankara, Turkey
`
`Disclosures
`
`The author indicated no financial relationships.
`
`REFERENCES
`
`1. Auchus RJ, Yu MK, Nguyen S et al. Use of prednisone with abiraterone
`acetate in metastatic castration-resistant prostate cancer.The Oncologist 2014;
`19:1231–1240.
`
`2. Lorente D, Omlin A, Ferraldeschi R et al. Tumour responses following
`a steroid switch from prednisone to dexamethasone in castration-resistant
`prostate cancer patients progressing on abiraterone. Br J Cancer 2014;111:
`2248–2253.
`
`3. Bianchini D, Lorente D, Rodriguez-Vida A et al. Antitumour 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.
`
`4. Venkitaraman R, Lorente D, Murthy V et al. A randomised phase 2 trial of
`dexamethasone versus prednisolone in castration-resistant prostate cancer.
`Eur Urol 2015;67:673–679.
`
`5. Czock D, Keller F, Rasche FM et al. Pharmacokinetics and pharmacody-
`namics of systemically administered glucocorticoids. Clin Pharmacokinet 2005;
`44:61–98.
`
`6. Diederich S, Scholz T, Eigendorff E et al. Pharmacodynamics and
`pharmacokinetics of synthetic mineralocorticoids and glucocorticoids: Re-
`ceptor transactivation and prereceptor metabolism by 11beta-hydroxysteroid-
`dehydrogenases. Horm Metab Res 2004;36:423–429.
`
`http://dx.doi.org/10.1634/theoncologist.2014-0472
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`The Oncologist 2015;20:e13 www.TheOncologist.com
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`©AlphaMed Press 2015
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