title: A randomised phase 2 trial of dexamethasone versus prednisolone in castration-resistant prostate cancer.
abstract: Prednisolone is widely used as secondary hormonal treatment for castration-resistant prostate cancer (CRPC). We hypothesised that dexamethasone, another corticosteroid, is more active.
  
  
  
  To compare the activity of prednisolone and dexamethasone in CRPC.
  
  
  
  This single-centre, randomised, phase 2 trial was performed in 82 men with chemotherapy-naïve CRPC enrolled from 2006 to 2010.
  
  
  
  Prednisolone 5mg twice daily versus dexamethasone 0.5mg once daily versus intermittent dexamethasone 8mg twice daily on days 1-3 every 3 wk.
  
  
  
  The main end point was prostate-specific antigen (PSA) response rate. Secondary end points included time to PSA progression, radiologic response rate using Response Evaluation Criteria In Solid Tumors (RECIST), and safety.
  
  
  
  The intermittent dexamethasone arm was dropped after no response was seen in seven patients. By intention to treat, confirmed PSA response was seen in 41% versus 22% for daily dexamethasone versus prednisolone, respectively (p=0.08). In evaluable patients, the PSA response rates were 47% versus 24% for dexamethasone and prednisolone, respectively (p=0.05). Median time to PSA progression was 9.7 mo on dexamethasone versus 5.1 mo on prednisolone (hazard ratio: 1.6; 95% confidence interval, 0.9-2.8). In 43 patients with measurable disease, the response rate by RECIST was 15% and 6% for dexamethasone and prednisolone, respectively (p=0.6). Of 23 patients who crossed over at PSA progression on prednisolone, 7 of the 19 evaluable (37%) had a confirmed PSA response to dexamethasone. Clinically significant toxicities were rare.
  
  
  
  Dexamethasone may be more active than prednisolone in CRPC. In the absence of more definitive trials, dexamethasone should be used in preference to prednisolone.
  
  
  
  We compared two different steroids used for treating men with advanced prostate cancer. Our results suggest that dexamethasone may be more effective than prednisolone and that both are well tolerated.
  
  
  
  EUDRAC 2005-006018-16.
authors.affiliation: Ipswich Hospital NHS and University Campus Suffolk, Ipswich, UK.
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Venkitaraman
authors.affiliation: Institute of Cancer Research, Sutton, UK.
authors.forename: David
authors.initials: D
authors.lastname: Lorente
authors.affiliation: Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India.
authors.forename: Vedang
authors.initials: V
authors.lastname: Murthy
authors.affiliation: Royal Marsden Hospital, Sutton, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Thomas
authors.affiliation: Institute of Cancer Research, Sutton, UK.
authors.forename: Lydia
authors.initials: L
authors.lastname: Parker
authors.affiliation: Institute of Cancer Research, Sutton, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Ahiabor
authors.affiliation: Institute of Cancer Research, Sutton, UK.
authors.forename: David
authors.initials: D
authors.lastname: Dearnaley
authors.affiliation: Institute of Cancer Research, Sutton, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Huddart
authors.affiliation: Institute of Cancer Research, Sutton, UK.
authors.forename: Johann
authors.initials: J
authors.lastname: De Bono
authors.affiliation: Royal Marsden Hospital, Sutton, UK. Electronic address: chris.parker@rmh.nhs.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: Parker
mesh_terms: D000368:Aged; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D011239:Prednisolone; D017430:Prostate-Specific Antigen
keywords: Dexamethasone; Prednisolone; Prostate cancer