Effectiveness and Safety of Combination Therapy of Transarterial Chemoembolization and Apatinib for Unresectable Hepatocellular Carcinoma in the Chinese Population: A Meta-Analysis

Chemotherapy ◽  
2019 ◽  
Vol 64 (2) ◽  
pp. 94-104 ◽  
Author(s):  
Yan Wei ◽  
Jianjun Liu ◽  
Min Yan ◽  
Shuguang Zhao ◽  
Yong Long ◽  
...  

Background: The combination of transarterial chemoembolization (TACE) and apatinib has been used in the treatment of intermediate or advanced hepatocellular carcinoma (HCC). However, its effectiveness and safety are also argued. Methods: Eligible studies were collected from a computer search of literatures published from the database establishment to May 2019 in PubMed, Web of Science, EMBASE, Ovid, the Cochrane Library, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine Disc. The objective response rate (ORR), the disease control rate (DCR), survival rate (SR), and the incidences of treatment-related adverse effects (AEs) were collected as the relevant outcomes. Data were analyzed through fixed/random effects of meta-analysis models with RevMan 5.3 software. Results: Eight randomized controlled clinical trials comprising 528 patients and 4 cohort studies comprising 226 patients were eventually included. Compared to the control group treated with TACE solely, combination therapy group, in which intermediate or advanced HCC patients were treated with TACE and apatinib, significantly enhanced ORR (relative risk [RR] 2.06, 95% CI 1.63–2.61, p < 0.001), DCR (RR 1.65, 95% CI 1.24–2.20, p < 0.001), and whole SRs of 6-month (RR 1.52, 95% CI 1.08–2.14, p = 0.02), 1-year (RR 1.52, 95% CI 1.25–1.84, p < 0.001), and 2-year (RR 1.84, 95% CI 1.34–2.54, p < 0.001). The incidence of hand foot syndrome, proteinuria, hypertension, and diarrhea was significantly increased in the combination therapy group compared with the control group (p < 0.05), and the incidence of nausea and vomiting, fever, and myelosuppression, respectively, was similar in 2 groups (p > 0.05). Conclusions: The combination therapy of TACE and apatinib can enhance the clinical effectiveness better than TACE solely in patients with intermediate or advanced HCC, while increase in the AEs is usually tolerable.

2020 ◽  
Vol 18 ◽  
pp. 205873922096055
Author(s):  
Xiu-Heng Qi ◽  
Zhen-Ming Wu ◽  
Qi Liu ◽  
Qian Guo ◽  
Ling-Ling Wang ◽  
...  

To explore the effects of two different administration routes of Endostar on the survival of patients with medium and advanced hepatocellular carcinoma (HCC) and underwent trans-arterial chemoembolization (TACE). Seventy-two patients with medium and advanced HCC were enrolled. Among them, 42 patients underwent the hepatic arterial infusion of Endostar combined with TACE (infusion therapy group); and the remaining 30 patients underwent the hepatic treatment of TACE combined with the intravenous application of Endostar (intravenous therapy group). All patients underwent regular examinations of CT (or MRI) and DSA to observe the conditions of tumor recurrence or metastasis, and to determine the existence of tumor angiogenesis. The response rate of treatment in the Endostar hepatic arterial infusion group was higher than that in the control group, and the difference was statistically significant (31/42:14/30, X2 = 5.501, p < 0.05). In addition, median progression free-survival time of the two groups were 8.67 months and 6.67 months, respectively ( p = 0.046); and the difference was statistically significant. The hepatic arterial infusion of Endostar combined with TACE can significantly improve recent clinical efficacy and mPFS in the treatment of medium and advanced HCC. However, improvement on the overall survival of long-term efficacy is not significant.


2021 ◽  
Vol 11 ◽  
Author(s):  
Qinqin Liu ◽  
Nan You ◽  
Jing Li ◽  
Ke Wu ◽  
Xuehui Peng ◽  
...  

BackgroundHepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis. Immunotherapy has gained great interest for various solid tumors due to its promising clinical efficacy. Targeted therapy also plays a crucial role in anticancer treatment. However, studies on the combination of immunotherapy and targeted therapy for advanced HCC are limited. Thus, the objective of this study was to investigate the efficacy and safety of camrelizumab combined with sorafenib in the treatment of advanced HCC.MethodsFrom January 2019 to January 2021, 100 consecutive patients with advanced HCC in our hospital were enrolled for this study. Patients were assigned into two groups: a combined-therapy group (camrelizumab + sorafenib) and a sorafenib-only group. Progression-free survival (PFS), overall survival (OS), treatment response, and relevant adverse effects (AEs) were evaluated and recorded.ResultsOf a total of 100 patients, 35 received a combination of camrelizumab and sorafenib, and 65 were treated with sorafenib alone. After 1:1 propensity score matching (PSM), each group had 34 patients. The overall response rate (ORR) of the combined-therapy group was statistically significantly higher than that of the sorafenib-only group (before PSM, p = 0.037; after PSM, p = 0.010). However, there was no significant difference in disease control rate (DCR) between the two groups (before PSM, p = 0.695; after PSM, p = 1.000). Patients who received the combination therapy had significantly longer PFS than those who received the sorafenib monotherapy (before PSM, p = 0.041; after PSM, p = 0.043). However, the two groups exhibited comparable median OS (before PSM, p = 0.135; after PSM, p = 0.105). Although the combined-therapy group showed a higher incidence of AEs such as thrombocytopenia than the sorafenib-only group after PSM, most of these AEs were easily controlled after treatment.ConclusionCamrelizumab plus sorafenib showed favorable efficacy and manageable toxicity for patients with advanced HCC. However, more prospective randomized trials are necessary to further verify the potential clinical benefits of this combination therapy.


2019 ◽  
Vol 33 (6) ◽  
pp. 504-516 ◽  
Author(s):  
Ida Untari ◽  
Achmad Arman Subijanto ◽  
Dyah Kurnia Mirawati ◽  
Ari Natalia Probandari ◽  
Rossi Sanusi

Purpose The purpose of this paper is to conduct systematic reviews on Indonesian papers, to examine the most recent evidence of the efficacy of the combination of cognitive training and physical exercise, and to make recommendations in order to improve prevention, care and treatment services in elderly patients with mild cognitive impairment (MCI). Design/methodology/approach The databases of Cochrane, Medline, NIH (US National Library Medicine), ProQuest, EbscoHost, Clinical Key, EMBASE, Medical Librarian (TWE) in Ovid, Science Direct, Scopus, The Lancet Global Health, PubMed, Emerald, Indonesian National Library, Google Scholar, Google Indonesia, and Garuda Portal were systematically searched using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to obtain empirical papers published between June 1976 and January 2018. Findings Out of the 3,293 articles collected, 10 were included in this analysis. The result of this combined meta-analysis compares the combination therapy group (cognitive therapy and physical exercise) with a control group. It shows that the control group was likely to experience MCI 1.65 times more often than the combination therapy group. According to the result acquired from the synthesized meta-analysis, the control group experienced MCI 1.65 times higher than the combination therapy. The finding is proven to be statistically significant (95% CI= 1.42–1.93). Research limitations/implications The research considers only English and Indonesian articles. Practical implications It is important to explore the most effective training characteristics in a special combined intervention differentiated by the duration, frequency, intervention, type and combination mode. There is a need for further investigation that focuses on the physiological mechanisms underlying the positive effects, by inserting a more comprehensive neuro-imaging measurement to assess specifically the domain that benefits in terms of cognitive functions and molecular markers. Finally, exploratory studies are definitely required, which will specifically examine maintenance and treatment effects as well as derive theoretical explanations related to the interventions and predictors. Social implications A combination of cognitive training and physical exercise intervention may improve the global health or cognitive functions. Originality/value A combination of cognitive training and physical exercise has been found to improve prevention, care and treatment services in elderly patients with MCI. There is an increase in value in comparison to the study of Karssemeijer, which considered five Indonesian articles.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Zhoujing Cheng ◽  
Lin He ◽  
Yingjie Guo ◽  
Yuhua Song ◽  
Shasha Song ◽  
...  

Abstract Background To compare the efficacy of three types of palliative therapy for advanced hepatocellular carcinoma (HCC), including transarterial chemoembolisation (TACE) monotherapy, sorafenib alone and their combination. Methods The databases of PubMed, Embase and Cochrane Library were retrieved. The odds ratio (OR) with its 95% confidence interval (CI) was used to investigate the binary variables, and the standardised mean difference (SMD) with its 95% CI was employed to evaluate the continuous variables. All statistical tests were performed by using Stata/SE, version 12.0. Results Thirty-one clinical studies, containing 5125 unique cases of patients with advanced HCC, were included. There were significant improvements in overall survival (OS) (pooled SMD = 2.54; 95% CI 1.74–3.34) and time to progression (TTP) (pooled SMD = 2.49; 95% CI 0.87–4.12) of the patients after receiving the combination therapy of TACE and sorafenib, compared to TACE monotherapy, and the OS in the combined treatment cohort was also longer than that in the sorafenib-alone cohort (pooled SMD = 2.92; 95% CI 1.72–4.13). The combination therapy group in comparison to the TACE group benefited a significantly increased overall response rate (ORR) (pooled OR = 2.61; 95% CI 1.43–4.77), 1-year (pooled OR = 2.96; 95% CI 1.71–5.14) and 2-year (pooled OR = 1.64; 95% CI 1.18–2.28) survival rates and reduced disease progression rate (DPR) (pooled OR = 0.47; 95% CI 0.33–0.68); in parallel, the ORR in the group was also significantly higher than that in the sorafenib-alone group (pooled OR = 3.62; 95% CI 1.28–10.22), although without a difference in the DPR (pooled OR = 0.28; 95% CI 0.05–1.48). In addition, we discovered that the 1-year (pooled OR = 1.39; 95% CI 0.84–2.29) and 2-year (pooled OR = 1.70; 95% CI 0.69–4.18) survival rates in the TACE monotherapy cohort were not significantly different to those in the sorafenib-alone cohort. Conclusion The combination therapy is more effective than monotherapy in improving the prognostic outcomes of patients with advanced HCC. Therefore, we recommend it as the preferred treatment intervention for those patients.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2984
Author(s):  
Stepan M. Esagian ◽  
Christos D. Kakos ◽  
Emmanouil Giorgakis ◽  
Lyle Burdine ◽  
J. Camilo Barreto ◽  
...  

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3903-3903
Author(s):  
Jiang Ji ◽  
Zhao Wang ◽  
Bing Han

Introduction: Hypomethylating agents (HMA) azacitidine and decitabine were the first-line therapy for intermediate/ higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients unsuitable for hematopoietic cell transplantation (HSCT). HMA combined with chemotherapy was recently used to achieve for a better outcome. However, few studies were carried out to compare the HMA monotherapy to the HMA and chemotherapy combination therapy. This meta-analysis aimed to compare the efficacy, survival benefit and safety of HMA monotherapy and combination therapy (with chemotherapy) in patients with intermediate/high-risk MDS or AML. Methods: Related articles published between January 2009 and April 2019 were selected and patients were separated as monotherapy group and combination group for meta-analysis. To further eliminate the potential influence of differences in patients' baseline characteristic between the two groups, subgroups with similar patients' baseline characteristics were selected for further analysis. Complete response (CR) rate, overall response (ORR) rate, 1-year overall survival (OS) rate, 1-month death rate and the proportion of adverse event (AE) were pooled and compared. Results: 13 RCT or cohort studies with 997 patients (790 in monotherapy group, 207 in HMA combination group) were selected for meta-analysis. For the pooled data, there was no significant difference in sex and cytogenetic risk between the 2 groups, but the age of combination therapy group was significantly younger than that of the monotherapy group (61.3±13.2 year-old vs 67.7±10.2 year-old, p=0.000). The CR and ORR rate were significantly higher in combination therapy group (53% vs 17%, p=0.000 for CR and 67% vs 44%, p=0.000 for ORR). However, the 1-year OS (56% for combination therapy vs 51% for HMA monotherapy group, p=0.282) and 1-month death rate (5% for combination therapy vs 4% for HMA monotherapy group, p=0.965) were similar between the two groups. The incidence of CTCAE grade 3-4 infection and bleeding were significantly higher (infection: 50% for combination therapy vs 25.7% for monotherapy group, p=0.003; bleeding: 27.5%% for combination therapy vs 7.8% for monotherapy group, p=0.004) in combination group. In subgroup analysis, 117 and 179 patients were included in combination group and HMA monotherapy group, respectively. There was no significant difference in age (69.5±4.6 vs 69.0±6.8 years old, p=0.451) and proportion of favorable/intermediate cytogenetic risk (62% vs 71%, p=0.114) between the two groups, but a significantly lower proportion of male was found in combination therapy group (57% vs 74%, p=0.003). Although combination group had a higher CR rate (49% vs 17%, p=0.000), it had similar ORR rate (58% vs 49%, p=0.140) to monotherapy group. Meanwhile, combination therapy came with higher 1-month death rate (12% vs 3%, p=0.008) and lower 1-year OS (54% vs 68%, p=0.013) compared with monotherapy group. Conclusions: HMA combined with chemotherapy could increase CR rate in all patients and ORR rate in younger patients, but could not improve OS. For patients with similar older age, combination therapy could result in higher 1-month death rate and less 1-year OS. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 14 (2) ◽  
pp. 367-372 ◽  
Author(s):  
Tsai-Hung Yen ◽  
Chung-Hsin Chang ◽  
Sz-Iuan  Shiu

Tumor lysis syndrome (TLS) is a life-threatening emergency that usually develops in rapidly proliferating hematologic malignancies or advanced solid tumor following cytotoxic chemotherapy or therapeutic interventions. TLS is especially rare in patients with hepatocellular carcinoma (HCC). Therefore, we present a case of a female patient with newly diagnosed advanced HCC who developed TLS and hepatic failure after receiving combination therapy of nivolumab and sorafenib. To our knowledge, this is the first case of TLS in a patient with advanced HCC owing to combination therapy of nivolumab and sorafenib. We also reviewed the literature and summarized the characteristics of TLS in patients with advanced HCC receiving various therapeutic interventions. The overall mortality rate was 63% and regarding the management, transarterial chemoembolization (TACE) was the most common etiology. TACE-related TLS developed more rapidly than sorafenib-related TLS. Furthermore, the efficacy and safety of combination therapy of nivolumab and sorafenib should be further evaluated, and TLS should still be a concern, especially in patients with large tumor burden.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yun Huang ◽  
Zeyu Zhang ◽  
Weijun Liao ◽  
Kuan Hu ◽  
Zhiming Wang

Background and AimAlthough the treatment effect and availability of therapeutic options for advanced hepatocellular carcinoma (HCC) are limited, the downstaging strategy may improve patient prognosis. This study aimed to investigate the potential of combination therapy as a downstaging strategy for treating advanced HCC with portal vein tumor thrombus (PVTT).MethodsThis retrospective case series included patients having advanced HCC with PVTT, who received the combination therapy of sorafenib, camrelizumab, transcatheter arterial chemoembolization (TACE), and stereotactic body radiation therapy (SBRT) from January 2019 to December 2019 in Xiangya Hospital, Central South University. The downstaging rate, treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated.ResultsOf the 13 patients, HCC downstaging was achieved in 4 (33.3%) patients who later received hepatectomy. The overall response rate was 41.7%, and the disease control rate was 50.0%. The median PFS time was 15.7 months, with a 1-year PFS rate of 58.3%, whereas the median OS was not reached after 1 year (1-year OS, 83.3%). No severe adverse events or grade 3–4 adverse effect was observed in 12 of the 13 enrolled patients; therapy had to be discontinued in only one patient due to adverse events, who was excluded from the study. The most common adverse effect was fever (n = 4, 33.3%), followed by skin reaction (n = 3, 25%).ConclusionA combination therapy comprising sorafenib, camrelizumab, TACE, and SBRT is an effective downstaging strategy for advanced HCC with PVTT and is associated with few adverse events.


2021 ◽  
Author(s):  
Yue Hu ◽  
Tao Pan ◽  
Xi Cai ◽  
Quansheng He ◽  
Yubao Zheng ◽  
...  

Abstract BackgroundThe survival benefit and safety of transarterial chemoembolization (TACE) for advanced Hepatocellular Carcinoma (HCC) patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) is unclear. We aimed to investigate the efficacy and safety of TACE combined with TKIs and ICIs the treatment of advanced HCC. MethodsIn this study, the conditions of 147 patients with advanced HCC who underwent TKIs plus ICIs treatment between July 2017 and April 2020 were evaluated. We divided these patients into the TACE group and non-TACE group based on whether they were treated with TACE during TKIs plus ICIs treatment, and compared their survival outcomes, especially overall survival (OS), and whether they were exposed to unexpected toxicities. ResultsIn this study, a total of 98 patients who underwent TACE during TKIs plus ICIs treatment were included in the TACE group, while the other 49 patients were included in the non-TACE group. According to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST), the objective response rate (ORR) of the TACE group was higher than that of the non-TACE group (ORR 74.5% vs. 40.8%, p <0.001). The OS of the TACE group was significantly longer than the non-TACE group (OS 19.3 months vs. 10.8 months, p = 0.010). The incidence of grade 3-4 toxicities in the TACE group was similar to that in the non-TACE group (33.7% vs. 28.6%, p = 0.532). ConclusionsThe TACE treatment combined with TKIs plus ICIs resulted in longer OS compared to the treatment of systemic TKIs plus ICIs without TACE during the process of advanced HCC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Shukang He ◽  
Weichao Jiang ◽  
Kai Fan ◽  
Xiaobei Wang

BackgroundHepatocellular carcinoma (HCC) is often diagnosed at an advanced stage where only systemic treatment can be offered. The emergence of immune checkpoint inhibitors (ICIs) provides hope for the treatment of HCC. In this study, we performed a meta-analysis to provide evidence for the efficacy and safety of ICIs in the treatment of HCC.MethodsThe following databases and websites were searched: Embase, PubMed, Cochrane Library and ClinicalTrials.gov. The primary endpoints were response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).ResultsFinally, twelve studies were included in this meta-analysis. When the corresponding outcome indicators and their 95% confidence intervals (CIs) were pooled directly, the overall RR, DCR, PFS and OS were 0.17 (0.15-0.19, I2 = 56.2%, P=0.009), 0.58 (0.55-0.61, I2 = 75.9%, P&lt;0.001), 3.27 months (2.99-3.55, I2 = 73.0%, P=0.001), 11.73 months (10.79-12.67, I2 = 90.3%, P&lt;0.001). Compared to the control group, treatment with ICIs significantly improved RR, PFS and OS, the OR and HRs were 3.11 (2.17-4.44, P&lt;0.001), 0.852 (0.745-0.974, P=0.019) and 0.790 (0.685-0.911, P=0.001), respectively. However, no significant improvement in DCR was found in ICIs treatment in this meta-analysis.ConclusionHCC patients would benefit from ICIs treatment, however, more studies are needed in the future to provide more useful evidence for the treatment of HCC by programmed death-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors.


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