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肝动脉灌注化疗诱导治疗可提高乐伐替尼和PD1抑制剂治疗门静脉肿瘤血栓形成的肝细胞癌患者的疗效。

Induction therapy with hepatic arterial infusion chemotherapy enhances the efficacy of lenvatinib and pd1 inhibitors in treating hepatocellular carcinoma patients with portal vein tumor thrombosis.

作者信息

Fu Yizhen, Peng Wei, Zhang Weixiang, Yang Zhenyun, Hu Zili, Pang Yanxun, Hu Dandan, Chen Jinbin, Wang Juncheng, Zhou Zhongguo, Xu Li, Chen Minshan, Zhang Yaojun

机构信息

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People's Republic of China.

Department of Liver Surgery, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People's Republic of China.

出版信息

J Gastroenterol. 2023 Apr;58(4):413-424. doi: 10.1007/s00535-023-01976-x. Epub 2023 Mar 9.

Abstract

BACKGROUND

Hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX), lenvatinib and programmed death receptor-1 signaling inhibitors (PD1s) all alone have been proven effective in treating advanced hepatocellular carcinoma (HCC), yet the efficacy and safety of the tri-combination therapy in treating HCC patients with portal vein tumor thrombosis (PVTT) remains unknown.

METHODS

In this retrospective study, HCC patients with PVTT received either induction therapy of HAIC and lenvatinib plus PD1s in the initial period of treatment and then dual maintenance therapy of lenvatinib and PD1s (HAIC-Len-PD1) or continuous lenvatinib combined with PD1s (Len-PD1).

RESULTS

In total, 53 and 89 patients were enrolled into the Len-PD1 group and HAIC-Len-PD1 group, respectively. The median overall survival times were 13.8 months in the Len-PD1 group and 26.3 months in the HAIC-Len-PD1 group (hazard ratio (HR) = 0.43, P < 0.001). The median progression-free survival (PFS) time was significantly longer in the HAIC-Len-PD1 group than in the Len-PD1 group (11.5 months versus 5.5 months, HR = 0.43, P < 0.001). Induction therapy showed an objective response rate (ORR) 3 times higher than lenvatinib combined with PD1s therapy (61.8% versus 20.8%, P < 0.001), and exhibited inspiring intra- and extra-hepatic tumor control ability. Induction therapy led to more adverse events than lenvatinib combined with PD1s therapy, most of which were tolerable and controllable.

CONCLUSION

The induction therapy of FOLFOX-HAIC and lenvatinib plus PD1s is an effective and safe treatment for HCC patients with PVTT. The concept of induction therapy could be applied to other local-regional treatments and drugs combinations in HCC management.

摘要

背景

氟尿嘧啶、亚叶酸钙和奥沙利铂(FOLFOX)的肝动脉灌注化疗(HAIC)、乐伐替尼以及程序性死亡受体-1信号抑制剂(PD1)单独使用均已被证明对治疗晚期肝细胞癌(HCC)有效,但三联联合疗法治疗门静脉癌栓(PVTT)的HCC患者的疗效和安全性仍未知。

方法

在这项回顾性研究中,患有PVTT的HCC患者在治疗初期接受HAIC和乐伐替尼加PD1的诱导治疗,然后接受乐伐替尼和PD1的双重维持治疗(HAIC-Len-PD1)或持续的乐伐替尼联合PD1治疗(Len-PD1)。

结果

Len-PD1组和HAIC-Len-PD1组分别纳入了53例和89例患者。Len-PD1组的中位总生存时间为13.8个月,HAIC-Len-PD1组为26.3个月(风险比(HR)=0.43,P<0.001)。HAIC-Len-PD1组的中位无进展生存(PFS)时间明显长于Len-PD1组(11.5个月对5.5个月,HR=0.43,P<0.001)。诱导治疗的客观缓解率(ORR)比乐伐替尼联合PD1治疗高3倍(61.8%对20.8%,P<0.001),并表现出令人鼓舞的肝内和肝外肿瘤控制能力。诱导治疗导致的不良事件比乐伐替尼联合PD1治疗更多,其中大多数是可耐受和可控的。

结论

FOLFOX-HAIC和乐伐替尼加PD1的诱导治疗是治疗伴有PVTT的HCC患者的一种有效且安全的治疗方法。诱导治疗的概念可应用于HCC治疗中的其他局部区域治疗和药物联合。

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