Adis, a Wolters Kluwer Business, Auckland, New Zealand.
Drugs. 2011 Oct 22;71(15):2067-77. doi: 10.2165/11208080-000000000-00000.
Oral abiraterone acetate, in combination with prednisone/prednisolone, is used to treat patients with metastatic castration-resistant prostate cancer (CRPC) who have previously received docetaxel-containing chemotherapy. Abiraterone acetate was developed to specifically inhibit cytochrome P450 (CYP)17A1, which is an essential enzyme in the biosynthesis of testosterone. In a pivotal phase III trial in patients with metastatic CRPC who have previously received docetaxel-containing chemotherapy, abiraterone acetate 1000 mg once daily plus prednisone 5 mg twice daily significantly prolonged overall survival compared with placebo plus prednisone. In this trial, abiraterone acetate plus prednisone was significantly more effective than placebo plus prednisone in prolonging the time to prostate-specific antigen (PSA) progression and in prolonging progression-free survival. Significantly more abiraterone acetate plus prednisone recipients than placebo plus prednisone recipients were considered to be responders, when assessed by PSA levels or radiographic imaging. Treatment with abiraterone acetate plus prednisone in the phase III trial was associated with an acceptable tolerability profile, which was generally similar to that of the placebo plus prednisone group. However, adverse events of special interest (e.g. cardiac disorders and liver-function test abnormalities and adverse events resulting from elevated mineralocorticoid levels because of CYP17A1 inhibition [i.e. fluid retention and oedema, hypokalaemia, hypertension]) occurred in significantly more abiraterone acetate plus prednisone than in placebo plus prednisone recipients.
醋酸阿比特龙口服剂与泼尼松/强的松联合使用，用于治疗先前接受过含多西紫杉醇化疗的转移性去势抵抗性前列腺癌（CRPC）患者。醋酸阿比特龙的开发是为了专门抑制细胞色素 P450（CYP）17A1，这是睾丸激素生物合成中的一种必需酶。在一项先前接受过含多西紫杉醇化疗的转移性 CRPC 患者的关键 III 期试验中，醋酸阿比特龙 1000mg 每日一次加泼尼松 5mg 每日两次与安慰剂加泼尼松相比，显著延长了总生存期。在这项试验中，醋酸阿比特龙加泼尼松在延长前列腺特异性抗原（PSA）进展时间和无进展生存期方面明显比安慰剂加泼尼松更有效。根据 PSA 水平或影像学评估，与安慰剂加泼尼松组相比，更多的醋酸阿比特龙加泼尼松组患者被认为是应答者。在 III 期试验中，醋酸阿比特龙加泼尼松治疗的耐受性良好，与安慰剂加泼尼松组的耐受性相似。然而，特殊关注的不良事件（如心脏疾病和肝功能试验异常以及由于 CYP17A1 抑制导致的升高的盐皮质激素水平引起的不良事件[即体液潴留和水肿、低钾血症、高血压]）在醋酸阿比特龙加泼尼松组中明显多于安慰剂加泼尼松组。
