Background
To establish the maximum tolerated dose of abiraterone acetate plus prednisone (AA) combined with salvage radiotherapy (SRT) and goserelin in a phase 1 study in men with rising PSA following radical prostatectomy.
Conclusions
When AA was administered without goserilin, only 78% achieved castration levels. AA combined with SRT and goserilin did not increase pelvic toxicity, but lead to an unsuspected high frequency of grade 3 liver toxicity. The phase II recommended dose of AA combined to goserelin and SRT is 750 mg.
Methods
AA was given during one month before SRT at 1000 mg PO once daily, then 750 mg (Dose Level 1, DL1) or 1000 mg (DL2) during 5 months combined with 6-months goserelin by injection on the first day of irradiation (scheme NEO) or one month before starting SRT (scheme CONCO).
Results
In scheme NEO at DL1, 2/9 patients did not achieve castration levels of testosterone. 4/9 patients (44%) presented with grade 3 liver enzyme elevation. In scheme CONCO testosterone dropped to undetectable levels. At DL1, 6 patients were recruited, with no dose limiting toxicities. At DL2, 2/3 patients presented with grade 3 liver enzyme elevation occurring during SRT. Conclusions: When AA was administered without goserilin, only 78% achieved castration levels. AA combined with SRT and goserilin did not increase pelvic toxicity, but lead to an unsuspected high frequency of grade 3 liver toxicity. The phase II recommended dose of AA combined to goserelin and SRT is 750 mg.