Fatal adverse events with molecular targeted agents in the treatment of advanced hepatocellular carcinoma: a meta-analysis of randomized controlled trials

Li, Xiaofei; Jia, Wei‐Hua; Wu, Zhenping; Tu, Juncai; Hu, Yongtao; Wu, Shuang; Lou, Lianqing

doi:10.2147/dddt.s151241

Cited by 7 publications

(6 citation statements)

References 34 publications

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“…HCC is the most common type of primary liver cancer, since most patients are already in advanced or metastasized stages at the time of initial diagnosis, which causes serious health problems worldwide. 18 Although various treatment strategies have been developed, including surgical resection, trans-arterial chemoembolization, 19 molecular-targeted drugs, 20 radiofrequency ablation, and liver transplantation, the prognosis of HCC remains unsatisfactory. 21 XJR is an effective antitumor prescription created by traditional Chinese medicine master Zhou Zhongying, through years of clinical practice experience.…”

Section: Discussionmentioning

confidence: 99%

Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis

Qiu¹,

Wang²,

Chen³

et al. 2020

CMAR

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Purpose Xiaoai Jiedu recipe (XJR), a formula long used by Chinese National Medical Professor Zhou Zhongying, has potent antitumor properties, but the molecular mechanism is still unclear. The aim of the study was to investigate the antitumor mechanism of XJR on hepatocellular carcinoma (HCC) by focusing on miRNA. Methods Three concentrations of XJR (low, middle, and high) were used to treat tumor xenograft mice models. Microarray technology was used to identify the differential expressed genes after XJR treatment, and bioinformatic tools and luciferase reporter assay to predict the potential pathways. HepG2 cells were transfected with inhibitor of miR-200b-3p to detect the effect of miR-200b-3p and Notch1 on tumor growth. Results XJR effectively exerted anti-HCC effect both in vitro and in vivo. MiRNA chip analysis results showed that the expression of 75 miRNAs was upregulated and 158 miRNAs was downregulated in blood from XJR-treated mice. Further validation by using real-time polymerase chain reaction (RT-PCR) assay showed that the expression of five miRNAs (miR-453, miR-200b-3p, miR-135a-1-3p, miR-1960, miR-378a-5p, and miR-466f) was consistent with the results of miRNA chip analysis. Among them, miR-200b-3p was selected as candidate for further research. Results of the MTT, migration, and wound healing assays showed that down-expression of miR-200b-3p abrogated the effect of XJR on cell growth and metastasis. Luciferase reporter assay confirmed that Notch1 was the direct target of miR-200b-3p. XJR significantly decreased Notch1 expression in HepG2 cells, whereas miR-200B-3p inhibitor abrogated the XJR-induced decrease in Notch1 expression. Conclusion This study indicated that XJR could effectively inhibit HCC and might exert its antitumor effect through the miR‐200b-3p/Notch1 axis. These findings provided new avenues for the use of XJR for prevention and treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis

Qiu¹,

Wang²,

Chen³

et al. 2020

CMAR

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“…Vascular endothelial growth factor (VEGF) inhibitor treatment was found to be associated with an increased incidence of hemorrhage events, according to a meta-analysis [44,45]; the major frequent hemorrhage events were reported to be upper gastrointestinal hemorrhage and intracranial hemorrhage [46]. Indeed, intracranial hemorrhage was found in three patients that were treated with lenvatinib in the REFLECT trial [12].…”

Section: The Hemorrhage Eventsmentioning

confidence: 99%

Lenvatinib for Hepatocellular Carcinoma: A Literature Review

2021

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Lenvatinib, which is an oral multikinase inhibitor, showed non-inferiority to the sorafenib in terms of overall survival (OS) and a higher objective response rate (ORR) and better progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). A good liver function and Barcelona Clinic Liver Cancer (BCLC) intermediate stage were the key factors in achieving therapeutic efficacy. The management of adverse events plays an important role in continuing lenvatinib treatment. While sequential therapies contributed to prolonging overall survival, effective molecular targeted agents for the administration after lenvatinib have not been established. Repeated transcatheter arterial chemoembolization (TACE) was associated with a decline in the liver function and poor therapeutic response in BCLC intermediate patients. Recently, the Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement proposed the criteria for TACE unsuitability. Upfront systemic therapy may be better for the BCLC intermediate stage HCC patients with a high tumor burden, while selective TACE will be recommended for obtaining a curative response in patients with a low tumor burden. This article reviews the therapeutic response, management of adverse events, post-progression treatment after Lenvatinib, and treatment strategy for BCLC intermediate stage HCC.

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“…There are some other reports about hemorrhagic events in HCC patients treated with MTAs. However, the major hemorrhagic events during MTA treatment are gastrointestinal hemorrhage, including variceal hemorrhage and intracranial hemorrhage [10, 11]. Thus, to the best of our knowledge, no previous report on HCC has identified tumor-related hemorrhage as an MTA-related AE other than our case reports [8].…”

Section: Discussion/conclusionmentioning

confidence: 71%

Lenvatinib-Induced Tumor-Related Hemorrhages in Patients with Large Hepatocellular Carcinomas

et al. 2020

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Introduction: Lenvatinib has been approved as a systemic therapy for patients with unresectable hepatocellular carcinoma (HCC). We recently experienced lenvatinib-induced tumor-related hemorrhage in patients with HCC. The full details of tumor-related hemorrhage as a lenvatinib-related adverse event have not been elucidated. Methods: This was a retrospective single-center study that enrolled consecutive patients treated with lenvatinib for unresectable HCC from April 2018 to February 2020. Results: Sixty-eight consecutive patients were enrolled in this study. Among them, 5 cases developed intraperitoneal or intratumoral hemorrhages. The patients with hemorrhage had larger tumors (maximum tumor size, 97.5 ± 46.4 and 38.2 ± 28.8 mm, respectively; p = 0.009) than the patients without hemorrhage. The dosing period of lenvatinib (median, 3 and 93 days, respectively; p < 0.001) and the survival time from initial administration of lenvatinib (median, 77 and 495 days, respectively; p < 0.001) of the patients with hemorrhage were shorter than those of the patients without hemorrhage. Especially, in 4 cases with large HCCs (maximum tumor diameter was >90 mm), tumor hemorrhage with vascular lake-like phenomenon was evident, although most tumor blood flow was suppressed. Discussion/Conclusion: It becomes clear that lenvatinib treatment brings about tumor-related hemorrhages despite rapid suppression of tumor blood flow. We speculate that lenvatinib quickly blocks the feeding circulation, resulting in tumor hemorrhage by necrosis. Clinicians should pay careful attention to the development of life-threatening hemorrhages when treating large HCCs with lenvatinib.

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Fatal adverse events with molecular targeted agents in the treatment of advanced hepatocellular carcinoma: a meta-analysis of randomized controlled trials

Cited by 7 publications

References 34 publications

<p>Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis</p>

<p>Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis</p>

Lenvatinib for Hepatocellular Carcinoma: A Literature Review

Lenvatinib-Induced Tumor-Related Hemorrhages in Patients with Large Hepatocellular Carcinomas

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