TACE plus sorafenib for the treatment of hepatocellular carcinoma: results of the multicenter, phase II SOCRATES trial

Erhardt, Andreas; Kolligs, Frank T.; Dollinger, Matthias; Schott, Eckart; Wege, H.; Bitzer, Michael; Gog, C.; Lammert, Frank; Schuchmann, M.; Walter, Clemens; Blondin, D.; Ohmann, Christian; Häussinger, Dieter

doi:10.1007/s00280-014-2568-8

Cited by 60 publications

(38 citation statements)

References 28 publications

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“…Sorafenib can inhibit TACE-induced tumor angiogenesis. Therefore, a combination of both may help to control tumors synergistically and has been employed in several studies with variable success [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Combined Transarterial Embolization/Chemoembolization-Based Locoregional Treatment with Sorafenib Prolongs the Survival in Patients with Advanced Hepatocellular Carcinoma and Preserved Liver Function: A Propensity Score Matching Study

et al. 2018

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Background: Sorafenib is the standard treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). However, the treatment outcome is not satisfactory. We retrospectively analyzed whether adding transarterial embolization/chemoembolization (TA(C)E)-based locoregional therapy to sorafenib can further improve treatment efficacy. Patients and Methods: We included 147 BCLC stage C HCC patients with Child-Turcotte-Pugh class A liver function and treated with sorafenib for analysis. Through propensity score matching, we divided patients into the combined treatment group (n = 63; patients received TA(C)E-based locoregional treatment and sorafenib) and the sorafenib monotherapy group (n = 63). We analyzed the effects of patients’ clinical and tumor-related factors on their overall survival (OS) and time to tumor progression. Results: The OS was better in the combined treatment group than in the sorafenib monotherapy group (419 vs. 223 days, p = 0.028). In the Cox regression model, combined treatment, a lower baseline α-fetoprotein (AFP) level < 400 ng/mL, tumors without main portal venous tumorous thrombosis, and age ≥60 years were identified as independent factors for OS. Subgroup analysis demonstrated that patients with a higher baseline AFP level > 400 ng/mL, age < 60 years, tumors with branched portal venous tumorous thrombosis only or without extrahepatic metastasis benefited the most from combined treatment. Conclusion: Combining TA(C)E-based locoregional treatment with sorafenib resulted in better OS in patients with BCLC stage C HCC compared with sorafenib alone. TA(C)E-based locoregional treatment can be an adjunctive treatment to sorafenib for patients with advanced HCC and a satisfactory liver functional reserve.

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Section: Introductionmentioning

confidence: 99%

Combined Transarterial Embolization/Chemoembolization-Based Locoregional Treatment with Sorafenib Prolongs the Survival in Patients with Advanced Hepatocellular Carcinoma and Preserved Liver Function: A Propensity Score Matching Study

et al. 2018

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“…A recent review and meta-analysis reported that this combined approach may bring benefit to unresectable HCC in terms of TTP but not OS[37]. Recent studies (START, SOCRATES) that investigated the efficacy and safety of Sorafenib as an adjuvant to TACE displayed good tolerability and interesting response rate[38,39]. Clearly a better defined population of advanced HCC -that might have the maximal benefit from this approach- should be tested in clinical trial.…”

Section: The Story Of Near-failed Systemic Treatmentsmentioning

confidence: 99%

Systemic treatment for hepatocellular carcinoma: Still unmet expectations

Samonakis¹

2017

WJH

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Many patients with hepatocellular carcinoma (HCC) are diagnosed in an advanced stage, so they cannot be offered the option of curative treatments. The results of systemic chemotherapy are unsatisfactory and this has led to molecular targeted approaches. HCC develops in chronically damaged tissue due to cirrhosis in most patients. Several different cell types and molecules constitute a unique microenvironment in the liver, which has significant implications in tumor development and invasion. This, together with genome instability, contributes to a significant heterogeneity which is further enhanced by the molecular differences of the underlying causes. New classifications based on genetic characteristics of the tissue microenvironment have been proposed and key carcinogenic signaling pathways have been described. Tumor and adjacent tissue profiling seem biologically promising, but have not yet been translated into clinical settings. The encouraging first results with molecular - genetic signatures should be validated and clinically applicable. A more personalized approach to modern management of HCC is urgently needed.

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“…In the phase II SOCRATES trial which was a multicenter study evaluating TACE plus sorafenib in 43 patients with unresectable HCC, the median TTP was 16.4 months, median OS was 20.1 months, and DCR of 74.4%. The most common adverse events were diarrhea, hand-foot syndrome, fatigue, decreased appetite, and alopecia [60]. The START trial, a phase II prospective single-arm multinational study of sorafenib in combination with doxorubicin-based TACE in patient with unresectable, reported median PFS of 384 days (12.8 months), median TTP of 415 days (13.8 months), and 3-year OS of 86.1% with the most common grade 3 or worse adverse events were hand-foot syndrome and thrombocytopenia.…”

Section: Molecularly Targeted Agentmentioning

confidence: 99%

Hepatocellular Carcinoma: Past and Future of Molecular Target Therapy

2015

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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer related mortality worldwide. The incidence of HCC has been increasing annually. Viral infection, alcohol usage, and other causes of cirrhosis have been identified as major risk factors for HCC development. The underlying pathogenesis has not been as well defined. There have been multiple hypotheses to the specific mechanisms of hepatocarcinogenesis and they share the common theme of chronic inflammation, increase oxidative stress, and genomic alteration. Therapeutic options of HCC have been primarily local and/or regional including transplantation, resection, and radial frequency ablation, chemoembolization or radio-embolization. For unresectable or metastatic disease, the options are limited. Conventional chemotherapeutic options have been noted to have limited benefit. Sorafenib has been the one and only systemic therapy which has demonstrated modest overall survival benefit. This has led to more extensive research with focus on targeted therapy. Numerous pre-clinical and early phase clinical studies have been noted but failed to show efficacy in later phase clinical trials. In an effort to identify new potential therapeutic options, new understanding of underlying pathways to hepatocarcinogenesis should be one of the main focuses. This leads to development of more molecularly targeted agents to specific pathways, and immunotherapy. This article provides a review of major studies of molecular targeted agents which attempts to target these specific pathways in HCC.

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TACE plus sorafenib for the treatment of hepatocellular carcinoma: results of the multicenter, phase II SOCRATES trial

Abstract: Combination treatment of TACE and sorafenib in the present trial was tolerable and associated with an interesting response rate, TTP and OS. Combination therapies will probably close gaps in the present mono therapy driven treatment guidelines for locally advanced HCC.

Cited by 60 publications

References 28 publications

Combined Transarterial Embolization/Chemoembolization-Based Locoregional Treatment with Sorafenib Prolongs the Survival in Patients with Advanced Hepatocellular Carcinoma and Preserved Liver Function: A Propensity Score Matching Study

Combined Transarterial Embolization/Chemoembolization-Based Locoregional Treatment with Sorafenib Prolongs the Survival in Patients with Advanced Hepatocellular Carcinoma and Preserved Liver Function: A Propensity Score Matching Study

Systemic treatment for hepatocellular carcinoma: Still unmet expectations

Hepatocellular Carcinoma: Past and Future of Molecular Target Therapy

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