Gustave Roussy, Université Paris-Saclay, Oncology Medicine Department, Villejuif, F-94805, France.
Department of Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
Eur J Cancer. 2020 Apr;129:117-122. doi: 10.1016/j.ejca.2020.01.017. Epub 2020 Mar 6.
Abiraterone acetate (abiraterone) combined with prednisone is a standard of care in metastatic castration-resistant prostate cancer. Recently, benefit in overall survival was reported in metastatic castration-sensitive prostate cancer also, and an extension of indication has been granted. Abiraterone is seldom associated with liver toxicity. The clinical management and the outcome of patients with transaminase increase while on abiraterone have not been described.
We identified 25 men with metastatic prostate cancer and liver function test disorders occurring while on abiraterone treatment from December 2009 to September 2017 in three oncology centres in France.
Forty-six liver disorder events occurred in 25 patients while on abiraterone treatment. The median age at liver function test increase was 67 (55-85) years. The incidence of aspartate aminotransférase (AST) (24 events) and that of alanine aminotransférase (ALT) (22 events) increases were similar. Liver toxicity was of grade 1, 2 and 3 (Common Terminology Criteria for Adverse Events. version 4) in 7 (32%), 6 (27%) and 9 (41%) patients for ALT, and in 12 (50%), 6 (25%) and 6 (25%) for AST, respectively. The median time from abiraterone initiation to the detection of liver toxicity was 7.1 (4-95) weeks. The median time from highest ALT/AST increase to normalisation was 6.2 [2-14] weeks. In 13 patients (52%), liver tests spontaneously returned to baseline values, while abiraterone was continued at full dose.
Liver function test increase is a rare event that typically occurs within the first two months on abiraterone. Most patients experience normalisation of the tests, either spontaneously or after dose reduction/discontinuation.
醋酸阿比特龙（阿比特龙）联合泼尼松是转移性去势抵抗性前列腺癌的标准治疗方法。最近，转移性去势敏感性前列腺癌的总生存期也有获益的报道，适应证也得到了扩展。阿比特龙很少引起肝毒性。目前尚未描述接受阿比特龙治疗时出现转氨酶升高的患者的临床处理和结局。
我们在法国的三个肿瘤中心，从 2009 年 12 月至 2017 年 9 月期间，共确定了 25 例转移性前列腺癌患者在接受阿比特龙治疗时出现肝功能检查异常。
25 例患者中有 46 例出现与阿比特龙治疗相关的肝功能异常事件。转氨酶升高患者的中位年龄为 67（55-85）岁。天门冬氨酸氨基转移酶（AST）（24 例）和丙氨酸氨基转移酶（ALT）（22 例）升高的发生率相似。ALT 肝毒性按不良事件常用术语标准（第 4 版）分级为 1 级、2 级和 3 级的患者分别为 7（32%）、6（27%）和 9（41%），AST 分别为 12（50%）、6（25%）和 6（25%）。从开始使用阿比特龙到检测到肝毒性的中位时间为 7.1（4-95）周。从 ALT/AST 升高的最高值到恢复正常的中位时间为 6.2[2-14]周。在 13 例患者（52%）中，肝功能检查值自发恢复到基线值，同时继续全剂量使用阿比特龙。
肝功能检查异常是一种罕见事件，通常发生在开始使用阿比特龙后的前两个月内。大多数患者的检查结果可自行恢复正常，或者在减少剂量/停药后恢复正常。
