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The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma.

ABSTRACT: Standard of practice involves using transarterial therapy for multifocal hepatocellular carcinoma (HCC) alone and sorafenib only for more advanced HCC, but the sorafenib and transarterial therapy combination may provide greater efficacy.To evaluate the safety and efficacy of concurrent sorafenib and transarterial therapy in HCC.Consecutive cases of HCC were treated with sorafenib and transarterial therapy, receiving sorafenib 2 to 4weeks before transarterial therapy. Baseline clinical parameters, adverse events (AEs) and survival were collected.A total of 47 patients received sorafenib and transarterial therapy. The majority of the patients were male (70%) with HCV (60%), median age of 60years, good performance status (0-1), stable cirrhosis (Child: A 72%; B 28%), unresectable tumour (stage: B 81%; C 19%) and median AFP of 24ng/mL. Median follow-up was 12months and median time on sorafenib was 6months. LC Bead TACE was used with a median frequency of 3. The majority of the patients (89%) experienced AEs. The most common AEs were fatigue (51%), hand-foot skin reaction (51%) and diarrhoea (43%). Grade 3 and 4 AEs included fatigue (13%) and hand-foot skin reaction (26%). Most patients required a dose reduction (66%). The main AE related to transarterial therapy was post-TACE syndrome (23%). The disease control rate was 68% at 6months. Overall median survival rate was 18.5months (95% CI 16.1-20.9months).Concurrent sorafenib and transarterial therapy is overall safe with no unexpected side effects and encouraging efficacy that warrants further study.

SUBMITTER: Cabrera R

PROVIDER: S-EPMC3807574 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma.

Cabrera R R Pannu D S DS Caridi J J Firpi R J RJ Soldevila-Pico C C Morelli G G Clark V V Suman A A George T J TJ Nelson D R DR

Alimentary pharmacology & therapeutics 20110523 2

<h4>Background</h4>Standard of practice involves using transarterial therapy for multifocal hepatocellular carcinoma (HCC) alone and sorafenib only for more advanced HCC, but the sorafenib and transarterial therapy combination may provide greater efficacy.<h4>Aim</h4>To evaluate the safety and efficacy of concurrent sorafenib and transarterial therapy in HCC.<h4>Methods</h4>Consecutive cases of HCC were treated with sorafenib and transarterial therapy, receiving sorafenib 2 to 4weeks before tran ...[more]

PMID: 21605146

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Project description: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.

Project description:BackgroundRecommended as the first-line treatment for advanced unresectable hepatocellular carcinoma (HCC), sorafenib has been shown to prolong median overall survival (OS) for patients. However, advanced HCC sees high heterogeneity across patient groups. Recently, a growing number of studies have indicated surgical resection and transarterial chemoembolisation (TACE) to perform well in patients with portal vein tumor thrombosis (PVTT). The aim of this study was to compare the outcomes of liver resection and TACE and to identify prognostic factors related to OS for BCLC stage C patients with performance status (PS) 1 who have a single tumor but no vascular invasion or extrahepatic spread.MethodsA total of 323 consecutive patients in BCLC stage C with PS 1 who had only one tumor and no vascular invasion or extrahepatic spread were enrolled in this retrospective study, regardless of tumor size. Survival analyses were performed using the Kaplan-Meier analysis, and statistical differences between the TACE and sorafenib groups were examined by the log-rank test. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS.ResultsBased on the Kaplan-Meier curves, patients treated with surgical resection showed a better OS than those who underwent TACE, with OS at 1, 3, and 5 years (85.7%, 48.8%, and 33.3% vs. 66.6%, 21.8%, and 13.4%, respectively; log-rank P<0.001). Univariate and multivariate analyses demonstrated that tumor size, albumin, bilirubin, Child-Pugh score, and treatment method were significant prognostic factors for OS. According to the subgroup analyses based on tumor size, there were significant differences in OS among overall subsets between patients who underwent hepatectomy and those who underwent TACE therapy.ConclusionsLiver resection had a better prognostic performance than TACE and should be put forward as an alternative treatment modality to TACE for BCLC stage C patients with PS 1 who have a single tumor and no vascular invasion or extrahepatic spread.

Project description:Objective:This study aimed at assessing the effects of transcatheter arterial chemoembolisation (TACE) and antiviral therapy on improving the prognosis of patients with hepatocellular carcinoma (HCC) after radical hepatectomy. Methods:This study reviewed the data of 120 patients with HCC who received either radical hepatectomy alone (control group), radical hepatectomy with postoperative TACE (TACE group) or radical hepatectomy with combined postoperative TACE, and antiviral therapy (combined group) from January 2000 to May 2015. To reduce the impact of the possible biases on the conclusion of this study to the minimum, the cases with similar demographic and clinicopathological characteristics were collected and 40 cases were assigned into each group. Recurrence, disease-free survival (DFS), and overall survival (OS) rates were compared. Results:Median follow-up period was 54.26?±?22.65 months with a range of 17-110 months. Recurrence after radical surgery was observed for 39 (97.5%) patients in the TACE group, 32 (80%) in the combined group, and 40 (100%) in the control group with median recurrence duration of 33, 43, and 16.5 months, respectively. Postoperative TACE with or without antiviral therapy significantly prolonged the DFS rate compared with radical hepatectomy alone (P = 0.000). TACE combined with antiviral therapy significantly extended the DFS rate compared with TACE alone (P = 0.008). Postoperative TACE with or without antiviral therapy also significantly prolonged the OS rate compared with radical hepatectomy alone (P = 0.000). In addition, antiviral therapy combined with TACE significantly extended the 5-year OS rate of patients compared with individual TACE and radical hepatectomy (67.5% versus 55% and 2.5%; P = 0.032). Conclusion:TACE is an appropriate therapy for HCC patients after radical hepatectomy. When combined with antiviral therapy, this treatment may further prolong the recurrence time and thus lead to high DFS and OS rates.

Project description:BackgroundSorafenib and transarterial chemoembolization (TACE) might both provide survival benefit for advanced hepatocellular carcinoma (HCC). Adopting either as a first-line therapy carries major cost and resource implications. We aimed to estimate the cost-effectiveness of sorafenib and TACE in advanced HCC.MethodsA Markov model was constructed in a hypothetical cohort of patients aged 60 years with advanced HCC and Child-Pugh A/B cirrhosis over a 2-year time frame. Three strategies (full or dose-adjusted sorafenib and TACE) were compared in two cost settings: China and the USA. Transition probabilities, utility and costs were extracted from systematic review of 27 articles. Sensitivity analysis and Monte Carlo analysis were conducted.ResultsFull and dose-adjusted sorafenib respectively produced 0.435 and 0.482 quality-adjusted life years (QALYs) while TACE produced 0.375 QALYs. The incremental cost-effectiveness ratio (ICER) of full-dose sorafenib versus TACE was $101,028.83/QALY in China whereas full-dose sorafenib is a dominant strategy (ICER of -$1,014,507.20/ QALY) compared with TACE in the USA. Compared to full-dose sorafenib, dose-adjusted sorafenib was the dominant strategy with the negative ICERs in both China (-$132,238.94/QALY) and the USA (-$230,058.09/QALY). However, dose-adjusted sorafenib is not available currently, so full-dose sorafenib should be compared with TACE. As the acceptability curves shown, full-dose sorafenib was the optimal strategy at the accepted thresholds of WTP in these two countries. Specifically, full-dose sorafenib was the cost-effective treatment compared with TACE if a WTP was set above $21,670 in the USA, whereas in China, TACE could be more favorable than full-dose sorafenib if a WTP was set below $10,473.ConclusionsDose-adjusted sorafenib may be cost-effective compared to full-dose sorafenib or TACE for advanced HCC patients. However, when confining the comparisons between full-dose sorafenib and TACE, full-dose sorafenib was cost-effective for these patients, under the accepted thresholds of WTP.

Project description:AimsThe purpose of the present study was to compare the efficacies of transarterial chemoembolization (TACE) combined with sorafenib versus TACE monotherapy for treating patients with advanced hepatocellular carcinoma (HCC).MethodsWe enrolled 321 patients and selected 280 with advanced HCC (Barcelona Clinic Liver Cancer stage C) who underwent TACE therapy between February 2009 and February 2013. TACE alone (monotherapy group) was administered to 198 patients (70.7%), and the remaining 82 (29.3%) underwent repeat combined TACE and sorafenib therapy (combined group). To minimize selection bias, these latter 82 patients were matched using propensity-score matching at a 1∶2 ratio with 164 patients who received TACE monotherapy. The primary endpoints were overall survival (OS) and related subgroup analysis. The secondary endpoints were time to progression (TTP) and treatment-related adverse events.ResultsOf the respective patients in the combined and monotherapy groups, 64.6% and 49.2% had vascular invasion, 87.8% and 91.1% had extrahepatic metastasis, and 54.3% and 47.1% had both. In the propensity-score-matched cohort, the OS survival of the combined group was significantly higher compared with the monotherapy group (7.0 months vs. 4.9 months, respectively, P = 0.003). The TTP was significantly longer in the combined group (2.6 months vs. 1.9 months, respectively, P = 0.001). Subgroup analysis showed that the outcomes of patients with advanced HCC without main portal vein invasion who were treated with combined therapy were significantly better compared with those who received monotherapy (P<0.05). Univariate and subsequent multivariate analyses revealed that the addition of sorafenib was an independent predictor of favorable OS and TTP (adjusted hazard ratios, 0.63 and 0.62, respectively; P<0.05 for both).ConclusionSorafenib plus TACE was more effective than TACE monotherapy for treating patients with advanced HCC without main portal vein invasion. Future trials with larger samples are required to validate these preliminary findings.

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The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma.

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The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma.

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