动脉化疗栓塞联合顺铂与表柔比星治疗肝细胞癌（ACE500 研究）：一项多中心、随机对照 2/3 期试验。
Arterial chemoembolisation with cisplatin versus epirubicin for hepatocellular carcinoma (ACE 500 study): A multicentre, randomised controlled phase 2/3 trial.
机构信息
Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.
Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan.
出版信息
Eur J Cancer. 2021 Nov;157:373-382. doi: 10.1016/j.ejca.2021.08.027. Epub 2021 Sep 23.
BACKGROUND
Transarterial chemoembolisation (TACE) is a treatment option for hepatocellular carcinoma (HCC), but the optimum agent for TACE remains unclear. We compared the efficacy of TACE with cisplatin versus with epirubicin in patients with unresectable HCC.
METHODS
This multicentre, randomised, phase 2/3 trial was performed at 21 hospitals in Japan. Patients with liver-confined HCC, performance status 0-2, and Child-Pugh class A/B were randomised to receive TACE with cisplatin or epirubicin. Patients were stratified in accordance with the institution, Child-Pugh class, tumour size, tumour thrombosis, α-fetoprotein and prior treatment. The primary end-point was overall survival in the intention-to-treat population. Tumour response was evaluated in accordance with the Response evaluation criteria in solid tumours criteria.
FINDINGS
Between 2008 and 2012, 455 patients were randomly assigned to undergo TACE with cisplatin (n = 228) or epirubicin (n = 227). Eleven patients were ineligible, and 444 patients were included in the full analysis. Twelve patients not receiving TACE were excluded, and 432 patients were included in the safety analysis set. In phase 2, disease control rates in cisplatin (91·7%) and epirubicin (91·8%) groups exceeded the predefined threshold of 70%, and the study proceeded to phase 3. After a median follow-up of 32·7 months (IQR = 15·3-49·3), median overall survival periods were 2·93 years (95% CI 2·60-3·79) and 2·74 years (95%CI 2·26-3·21), respectively (hazard ratio 0·90 [95% CI 0·71-1·15], p = 0·22). Median times to treatment failure were 1·38 and 1·46 years (hazard ratio 1·09 [95% CI 0·88-1·35], p = 0·88), response rates were 65·3% and 60·6% (p = 0·31), and serious adverse event rates were 49·8% and 48·3% (p = 0·56), respectively. No treatment-related deaths occurred in either group.
INTERPRETATION
In our phase 2/3 randomised trial, cisplatin is not significantly superior to epirubicin in TACE for patients with HCC.
背景
经导管动脉化疗栓塞术（TACE）是治疗肝细胞癌（HCC）的一种选择，但 TACE 的最佳药物仍不清楚。我们比较了顺铂与表柔比星用于不可切除 HCC 患者的 TACE 的疗效。
方法
这项多中心、随机、2/3 期试验在日本的 21 家医院进行。患有局限于肝脏的 HCC、表现状态 0-2 级和 Child-Pugh 分级 A/B 的患者被随机分配接受顺铂或表柔比星的 TACE。患者按照机构、Child-Pugh 分级、肿瘤大小、肿瘤血栓形成、α-胎蛋白和既往治疗进行分层。主要终点是意向治疗人群的总生存。根据实体瘤反应评价标准评估肿瘤反应。
结果
2008 年至 2012 年间，455 名患者被随机分配接受顺铂（n=228）或表柔比星（n=227）的 TACE。11 名患者不符合条件，444 名患者被纳入全分析集。12 名未接受 TACE 的患者被排除在外，432 名患者被纳入安全性分析集。在 2 期，顺铂（91.7%）和表柔比星（91.8%）组的疾病控制率超过了 70%的预设阈值，研究进入 3 期。中位随访 32.7 个月（IQR=15.3-49.3）后，中位总生存期分别为 2.93 年（95%CI 2.60-3.79）和 2.74 年（95%CI 2.26-3.21）（风险比 0.90 [95%CI 0.71-1.15]，p=0.22）。中位治疗失败时间分别为 1.38 年和 1.46 年（风险比 1.09 [95%CI 0.88-1.35]，p=0.88），反应率分别为 65.3%和 60.6%（p=0.31），严重不良事件发生率分别为 49.8%和 48.3%（p=0.56）。两组均未发生与治疗相关的死亡。
解释
在我们的 2/3 期随机试验中，顺铂在 TACE 治疗 HCC 患者中并不明显优于表柔比星。
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