Abstract
45 Background: Salvage radiotherapy (RT) plus 6 months LH-RH therapy (ADT) improves biochemical relapse free survival in men with rising PSA following prostatectomy. Abiraterone acetate (Aa) increases overall survival in metastatic prostate cancer. We aimed to establish the toxicity of adding Aa combined with salvage RT and 6 months goserilin (Gos). Methods: We enrolled pT2-pT4a pN0 prostate cancer patients (pts) with rising PSA (0.2 to <2.0 μg/l) following radical prostatectomy. The primary endpoint was to determine the Maximum Tolerated Dose and recommended dose of Aa during RT plus Gos, two dose levels tested : 1 (750mg) and 2 (1000 mg). Two different schemes were explored: Sheme A: Aa (1000 mg) and predisone (10 mg) were given orally during 1 month to salvage IMRT (66 Gy in 33 fractions). The first day of irradiation, Aa is reduced to level 1 or 2 and 10.8 mg Gos is injected (sc). In sheme B, Gos is injected the first day (1 month before starting RT). Results: We recruited 9 + 9 pts in scheme A and B respectively. In scheme A, Testosterone (Tst) levels declined to castration level (<0.5ng/ml) after 10 days . Two/9 pts did not achieve castration levels at 30 days. Median LH levels increased to 10.4 (D10) and 12.5 IU/l (D20). At dose level 1, 4/9 pts (44%) experienced grade 3 hepatitis, occurring prior to RT or during RT (8 Gy, 36 and 54 Gy). We hypothesized that this unexpected liver toxicity was related to the LH increase during the first month (Aa administration without Gos). Therefore, we modified LH-RH administration (scheme B) and recruited 9 more pts. Tst levels dropped to undetectable at day 6, while median LH levels decreased to 6.1 (D10) and 1.7 IU/l (D20). At dose level 1 (3 + 3 pts), no grade 3 liver toxicity was reported. No other grade 3 toxicity was recorded. At dose level 2, 2/3 pts had grade 3 hepatitis occurring during RT. CYP17 polymorphism did not correlate with liver toxicity. Conclusions: The recommended dose of Aa combined to short-term androgen deprivation and salvage RT is 750 mg. Aa alone did lead to castration levels in 22% of pts.An unexpected high frequency of grade 3 liver toxicity was observed. Clinical trial information: NCT01780220.
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