A randomised phase 2 trial of dexamethasone versus prednisolone in castration-resistant prostate cancer.

BACKGROUND: Prednisolone is widely used as secondary hormonal treatment for castration-resistant prostate cancer (CRPC). We hypothesised that dexamethasone, another corticosteroid, is more active. OBJECTIVE: To compare the activity of prednisolone and dexamethasone in CRPC. DESIGN, SETTING, AND PARTICIPANTS: This single-centre, randomised, phase 2 trial was performed in 82 men with chemotherapy-naïve CRPC enrolled from 2006 to 2010. INTERVENTION: Prednisolone 5mg twice daily versus dexamethasone 0.5mg once daily versus intermittent dexamethasone 8mg twice daily on days 1-3 every 3 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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. CONCLUSIONS: Dexamethasone may be more active than prednisolone in CRPC. In the absence of more definitive trials, dexamethasone should be used in preference to prednisolone. PATIENT SUMMARY: 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. CLINICAL TRIAL REGISTRY: EUDRAC 2005-006018-16.