`
`
`
`differences in the activity of synthetic giucocorticoids at the
`glucocorticoid receptor level might also cause alterations in
`efficacy 16].
`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 (Clinica|Triais.gov ID NCT01867710, Abiraterone with
`Different Steroid Regimens for Side Effect Related to
`Mineralcorticoid Excess Prevention in Prostate Cancer Prior
`
`to Chemotherapy).
`Grass §3$2§}AR
`
`Department of Preventive Oncology, Hacettepe University Cancer
`Institute, Sihhiye, Ankara, Turkey
`
`Disclosures
`The author indicated no financial relationships.
`
`
`1. Auchus it}; Yu MK, Nguyen S et al. Use of prednisone with abiraterone
`acetate in metastaticcastration—resistant prostate cancer. The Oncoingist2014;
`19:1231—1240.
`
`2. Lorente D, Drniin A, Ferraldeschi R et al. Tumour responses following
`a steroid switch from prednisone to dexamethasone in castrationresistant
`prostate cancer patients progressing on abiraterone. Br] Cancer 201-1;13.1:
`2248-2253.
`
`3. Bianchini D, Lorente D, Rodriguez-Vida A et al. Antitumour activity of
`enzaiutamide (MDV3100) in patients with metastatic castratiomresistant
`prostate cancer (CRPC) pretreated with docetaxeé and ablraterone. Eur J
`Cancer 201450178-84.
`4. Venkitaraman R, Lorente D, Murthyv et al. A randomised phase 2 trial of
`dexamethasone versus prednisolone in castration—re5istant prostate cancer.
`Eur Uroi 201 5_:67:573—67'9.
`S. Czock D, Keller F, Rasche FM et al. Pharmacokinetics and pharmacody—
`namics ofsystemically administered giucocorticoids. Clin Pharmacokinet 2005;
`44:51-93.
`
`6. Diederich 5, Scholz T, Eigendorff E at al. Pharrnacodynamics and
`pharmacokinetics of synthetic mineralocorticoids and glucocortacoidsz Re—
`ceptortransactivation and prereceptor metabolism by 11beta—hydroxysteroid-
`dehvdrogenases. Horm Metab Res 2004;36:423-429.
`
`http://dx.doi.org/10.1634/theoncologistzo14-0472
`
`
`
`Otto
`
`J.‘x
`
`is Dexamethasone a Better Partner for
`
`Abiraterone Than Prednisolone?
`
`I read with great interest the article by Auchus et al. [13 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 abirateronevprednisolone,
`11 of 30 patients (39%) had confirmed 230% PSA decline after
`switching to dexamethasone with median time to PSA progression
`of 11.7 weeks. These resuits are comparable with the response
`rate (41%) and duration (2.8 months) with enzalutamide after
`abiraterone in CRPC treatment [3].
`that
`The second trial
`is a randomized phase 2 triai
`compared the efficacy of prednisolone (5 mg b.i.d.) and
`dexamethasone (0.5 mg/day) in chemotherapy—nai've patients
`with CRPC.
`In evaluabie patients, the PSA response rates
`were 47% versus 24% for dexamethasone and prednisolone,
`respectively (p : .05). Median time to PSA progression was 9.7
`monthsondexamethasoneversus5.1monthson prednisolone
`(hazard ratio, 1.6; 95% confidence interval, 0.9-2.3). Among
`patients who crossed overat 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 ha£f~life of dexamethasone is longer, which
`may result in more effective suppression of adrenocorticotro—
`pic hormone and more proficient antitumorai 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,
`
`
`
`‘Hie Oncologist 2015;20:e13 www.TheOncologist.com
`
`©A|phaMed Press 2015
`
`