Supiot Stéphane, Campion Loic, Pommier Pascal, Dore Mélanie, Palpacuer Clément, Racadot Séverine, Rio Emmanuel, Milano Gérard A, Mahier-Ait Oukhatar Céline, Carrie Christian
Departments of Radiation Oncology and Biostatistics, Institut de Cancérologie de l'Ouest, Nantes, France.
Department of Radiation Oncology, Centre Léon Berard, Lyon, France.
Oncotarget. 2018 Apr 24;9(31):22147-22157. doi: 10.18632/oncotarget.25189.
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.
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).
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.
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.
在一项1期研究中，确定醋酸阿比特龙加泼尼松（AA）联合挽救性放疗（SRT）和戈舍瑞林用于根治性前列腺切除术后前列腺特异性抗原（PSA）升高男性的最大耐受剂量。
在SRT前1个月给予AA，口服1000 mg，每日1次，然后在5个月内给予750 mg（剂量水平1，DL1）或1000 mg（DL2），并在放疗第一天（方案NEO）或开始SRT前1个月（方案CONCO）联合注射6个月的戈舍瑞林。
在方案NEO的DL1组，2/9的患者未达到睾酮去势水平。4/9的患者（44%）出现3级肝酶升高。在方案CONCO组，睾酮降至检测不到的水平。在DL1组，招募了6名患者，无剂量限制毒性。在DL2组，2/3的患者在SRT期间出现3级肝酶升高。
当AA与戈舍瑞林联合使用时，只有78%的患者达到去势水平。AA联合SRT和戈舍瑞林并未增加盆腔毒性，但导致了意料之外的高频率3级肝毒性。AA联合戈舍瑞林和SRT的II期推荐剂量为750 mg。
