DEXAMETHASONE MAY BE BETTER THAN PREDNISOLONE FOR PROSTATE CANCER

NEW YORK (Reuters Health) - Daily dexamethasone may be more effective than daily prednisolone against castration-resistant prostate cancer (CRPC), as measured by prostate-specific antigen (PSA), according to a new phase 2 trial.

The researchers say their study, published online on October 16 in European Urology, is the only completed randomized comparison of different corticosteroids in CRPC.

On intent-to-treat analysis, serum PSA responses were seen in 16 of 39 patients in the dexamethasone arm, compared with just eight of 36 in the prednisolone arm (41% vs. 22%, p=0.08), according to Dr. Ramachandran Venkitaraman of Ipswich Hospital NHS and University Campus Suffolk in the UK and colleagues.

The results were slightly more pronounced in an analysis of patients with at least two on-treatment PSA measurements at least one week apart, in whom the response rates were 47% (16 of 34) for dexamethasone and 24% (eight of 33) for prednisolone (p=0.05).

The report also highlighted that seven of 19 patients (36%) who crossed over to dexamethasone after PSA progression on prednisolone achieved a PSA response to dexamethasone.

"Taken together with the previous data on prednisolone and dexamethasone in CRPC, our study challenges current clinical practice," the researchers write. "In the absence of more definitive trials, dexamethasone should be used in preference to prednisolone."

They also suggest that, "Given that abiraterone, docetaxel, and cabazitaxel are all approved for use in CRPC in combination with prednisolone, future studies should explore the use of dexamethasone in combination with these agents."

The primary study group consisted of 75 patients (median age 67), with 39 randomized to receive oral dexamethasone 0.5 mg daily and 36 randomized to receive oral prednisolone 5 mg twice daily. (Initially, a third arm of seven patients had received intermittent dexamethasone, but recruitment to this arm was stopped after none of the patients achieved a PSA response.)

The median time to PSA progression was 9.7 months for patients in the dexamethasone arm versus 5.1 months in the prednisolone arm.

Of the 36 patients on prednisolone, 23 crossed over to dexamethasone following biochemical disease progression.

Clinically significant toxicities were uncommon in both treatment arms, and no significant differences were seen between the two arms in terms of safety and tolerability.

The study's limitations included its relatively small size, an inability to gain any insight into how dexamethasone might be more active against CRPC than prednisolone and the lack of crossover to prednisolone after disease progression on dexamethasone.

The authors also noted that they could not exclude the possibility that dexamethasone activity following disease progression on prednisolone represented a withdrawal response to stopping prednisolone.

Although it's possible that dexamethasone could be more effective than prednisolone when combined with other anti-cancer drugs, such an option "cannot be recommended on current data," Dr. Chris Marsden of the Royal Marsden Hospital in Sutton, Surrey, UK, who was not involved in the study, told Reuters Health by email.

SOURCE: http://bit.ly/1tZQn5G

Eur Urol 2014.