阿帕替尼联合调强放疗治疗不可切除肝细胞癌的探索性临床试验。
An exploratory clinical trial of apatinib combined with intensity-modulated radiation therapy for patients with unresectable hepatocellular carcinoma.
机构信息
Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
出版信息
Cancer Med. 2023 Jan;12(1):213-222. doi: 10.1002/cam4.4900. Epub 2022 May 27.
PURPOSE
To evaluate the clinical efficacy and safety of apatinib combined with intensity-modulated radiation therapy (IMRT) in patients with unresectable hepatocellular carcinoma (uHCC).
MATERIALS AND METHODS
Open-label, single-arm, exploratory clinical trial of apatinib combined with IMRT for uHCC patients. Patients aged 18-75 years with adequate hematological, liver, and renal functions and Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were enrolled in this study from March 2017 to September 2020. Patients were received IMRT (biological effective dose: 46-60 Gy) and continuous apatinib (250-500 mg/day) oral administration until HCC progression or unacceptable toxic effects. The endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and safety. The trial registration number is ChiCTR-OPC-17011890.
RESULTS
A total of 33 patients have taken part in the study. The median age was 58 years old (range 32-77), 27 (81.9%) patients were ECOG PS 0-1, and 28 (84.9%) patients were male. In addition, 25 (75.7%) patients suffered from hepatitis B, 32 cases (97.0%) were in Barcelona Clinic Liver Cancer (BCLC) Stages B-C, and eight (24.2%) had portal vein involvement. Moreover, 12 (36.4%) and 21 (63.6%) patients received apatinib as first-line and second or later-line therapy, respectively. The average follow-up was 11.4 months, the median PFS was 7.8 months (95% confidence interval: 3.9-11.7). The OS rates at 6 and 12 months were 96.7% and 66.2%. The ORR and DCR were 15.1% and 81.8%, respectively. Hepatic toxicity was the most common treatment-related adverse events in Grades 3-4 (12.1%). No radiation-induced liver disease and Grade 5 toxicity were recorded.
CONCLUSION
Apatinib combined with IMRT is a safe and effective method to improve PFS and DCR and has good anti-tumor activity in patients with uHCC.
目的
评估阿帕替尼联合调强放疗（IMRT）治疗不可切除肝细胞癌（uHCC）患者的临床疗效和安全性。
材料和方法
这是一项阿帕替尼联合 IMRT 治疗 uHCC 患者的开放性、单臂、探索性临床试验。2017 年 3 月至 2020 年 9 月，纳入了年龄在 18-75 岁之间、具有足够的血液学、肝脏和肾功能以及东部肿瘤协作组（ECOG）体能状态为 2 分或以下的患者。患者接受 IMRT（生物有效剂量：46-60Gy）和连续口服阿帕替尼（250-500mg/天）治疗，直至 HCC 进展或出现无法耐受的毒性作用。主要终点包括无进展生存期（PFS）、总生存期（OS）、疾病控制率（DCR）、客观缓解率（ORR）和安全性。试验注册号为 ChiCTR-OPC-17011890。
结果
共有 33 名患者参与了这项研究。中位年龄为 58 岁（范围 32-77 岁），27 名（81.9%）患者 ECOG PS 为 0-1，28 名（84.9%）患者为男性。此外，25 名（75.7%）患者患有乙型肝炎，32 例（97.0%）患者处于巴塞罗那临床肝癌（BCLC）分期 B-C，8 例（24.2%）患者存在门静脉侵犯。此外，12 名（36.4%）和 21 名（63.6%）患者分别接受阿帕替尼作为一线和二线或以后线治疗。平均随访时间为 11.4 个月，中位 PFS 为 7.8 个月（95%置信区间：3.9-11.7）。6 个月和 12 个月的 OS 率分别为 96.7%和 66.2%。ORR 和 DCR 分别为 15.1%和 81.8%。最常见的 3-4 级治疗相关不良事件是肝毒性（12.1%）。未记录到放射性肝损伤和 5 级毒性。
结论
阿帕替尼联合 IMRT 是一种安全有效的方法，可提高不可切除 HCC 患者的 PFS 和 DCR，并具有良好的抗肿瘤活性。
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