AA+P has shown to improve overall survival (OS) in large, randomized trial in the treatment of mCRPC both in pre and post-docetaxel setting. AA is a steroidal CYP17A1 inhibitor, which suppresses androgen synthesis. Because of secondary mineralocorticoid excess it is licensed in combination with P.
Based on previous data reporting responses following steroid switch upon progression during AA+P a prospective study in mCRPC pts was started. (Lorente at al BJC (2014) 111, 2248–2253).
23 mCRPC pts were treated with AA (1000 mg q.d.) and P (5 mg b.i.d). Pts characteristics were as follows: median age 73 (95% CI 69-77) years, median Gleason score 8 (7-9), time-span since diagnosis was median 5.6 (3.6-7.8) yrs and all pts. had previous docetaxel treatment and received concomitant androgen deprivation treatment. Pts were on AA+P therapy for median 11.4 (6.4-19.8) mos. In case of PSA progression steroid switch has been applied to dexamethasone (D) (0.5 mg q.d). The PSA progression-free survival on AA+D combination was 5 (3.7-5) mos. 13 (57%) pts are still on AA+D treatment. The OS for AA was 53 (39-53) mos.Table:
|Schedule||PSA progression-free survival (mos)||PSA (ng/ml) at start||PSA (ng/ml) nadir|
|95% CI||6.4 -19.8||30-129||13-98|
|95% CI||3.7 - 5||27-133||20-100|
During AA+P therapy >25% decrease in PSA occurred in 65% of pts and further decrease (>25%, compared to the nadir during AA+P treatment) has been seen in 26% pts during AA+D treatment.
D can induce further response during AA therapy by reversing glucocorticoid receptor activation or by superior activity of D administered even as a single agent. Our data supports that steroid switch may induce further PSA regression.
Clinical trial identification
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All authors have declared no conflicts of interest.