TACE with or without systemic therapy?

Dufour, Jean–François

doi:10.1016/j.jhep.2012.02.011

Cited by 22 publications

(19 citation statements)

References 16 publications

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“…Studies by Gillmore and colleagues (13) have demonstrated that the EASL and modified RECIST (mRECIST) responses at the first follow-up assessment after TACE are independently associated with survival. A new treatment modality of sorafenib combined with TACE (combination therapy) is considered an alternative for patients with unresectable hepatocellular carcinoma (17), and studies have demonstrated a favorable safety profile and a high disease control rate in patients with hepatocellular carcinoma who have received this combination therapy (18)(19)(20). In agreement with these previously published reports, a recent multicenter study led by our team found impressive benefits of combination therapy in patients with hepatocellular carcinoma, even among those with advanced disease (21).…”

Section: Introductionsupporting

confidence: 77%

EASL- and mRECIST-Evaluated Responses to Combination Therapy of Sorafenib with Transarterial Chemoembolization Predict Survival in Patients with Hepatocellular Carcinoma

Liu

Wang

Chen

et al. 2014

Clinical Cancer Research

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Purpose: Published studies have not investigated the suitability of Response Evaluation Criteria in Solid Tumors (RECIST), European Association for the Study of the Liver (EASL) criteria, and modified RECIST (mRECIST) for assessing the response of patients with hepatocellular carcinoma to treatment with sorafenib combined with transarterial chemoembolization. Here, we aimed to define the earliest time at which the response to combination therapy could be accurately assessed and validate the prognostic value of these criteria at this early posttherapy time point.Experimental Design: A total of 114 consecutive patients with hepatocellular carcinoma receiving combination therapy were retrospectively enrolled. The therapy response at different time points was assessed using RECIST, EASL, and mRECIST. Cox regression analysis and Kaplan-Meier curves were used to assess overall survival (OS) in the responders and nonresponders.Results: At the third follow-up (median, 94 days; range, 89-102 days) after therapy, the response rates obtained using EASL (50.6%) and mRECIST (51.6%) were greater than that obtained using RECIST (16.5%). The agreement was strong between the mRECIST and EASL results (k ¼ 0.9) but weak between mRECIST and RECIST (k ¼ 0.3). The EASL and mRECIST responses significantly correlated with survival. Risk reductions of 52% and 50% were observed for EASL and mRECIST responders, respectively, compared with nonresponders. However, no significant association between the treatment response and survival was observed using RECIST.Conclusions: The earliest time to evaluate the response to combination therapy is 3 months (median, 94 days) after therapy. EASL and mRECIST responses are independent predictors for OS at this early time point.

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Section: Introductionsupporting

confidence: 77%

EASL- and mRECIST-Evaluated Responses to Combination Therapy of Sorafenib with Transarterial Chemoembolization Predict Survival in Patients with Hepatocellular Carcinoma

Liu

Wang

Chen

et al. 2014

Clinical Cancer Research

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“…The combination of the (doxorubicin-loaded) spheres with systemic anti-angiogenic therapy has already been reported (9)(10)(11), and several phase II and III trials with oral sunitinib (SATURNE) or sorafenib are under way or completed (12,13). Sunitinib malate (SU11248) is available as an oral formulation from Pfizer (New York, New York) and was approved by the U.S. Food and Drug Administration in 2006 for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor (14).…”

Section: Introductionmentioning

confidence: 98%

Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

Fuchs

Bize

Dormond

et al. 2014

Journal of Vascular and Interventional Radiology

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Purpose: The combination of embolic beads with a multi-targeted tyrosine kinase inhibitor that inhibits tumor vessel growth is suggested as an alternative and improvement to the current standard doxorubicin-eluting beads for use in transarterial chemoembolization. This study demonstrates the in vitro loading and release kinetics of sunitinib using commercially available embolization microspheres, and evaluates the in vitro biological efficacy on cell cultures and the resulting in vivo pharmacokinetic profiles in an animal model. Materials and Methods:DC Bead microspheres, 70-150 µm and 100-300 µm (Biocompatibles Ltd., Farnham, United Kingdom), were loaded by immersion in sunitinib solution. Drug release was measured in saline in a USP-approved flow-through apparatus and quantified by spectrophotometry. Activity after release was confirmed in cell culture. For pharmacokinetics and in vivo toxicity evaluation, New-Zealand white rabbits received sunitinib either by intra-arterial injection of 100-300 µm sized beads or per os. Drug concentrations in the plasma and liver tissue were assessed by liquid chromatography-tandem mass spectrometry.Results: Sunitinib loading on beads was close to complete and homogeneous. A total release of 80% in saline was measured, with similar fast release profiles for both sphere sizes. After embolization, drug plasma levels remained below the therapeutic threshold (< 50 ng/ml), but high concentrations at 6 h (14.9 µg/g) and 24 h (3.4 µg/g) were found in the liver tissue.Conclusions: DC Bead microspheres of two sizes were efficiently loaded with sunitinib and displayed a fast and almost complete release in saline. High liver drug concentrations and low systemic levels indicated the potential of sunitinib-eluting beads for use in embolization.

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“…In the smaller Italian SOFIA study, the OS of the 74 BCLC-B patients treated with sorafenib was longer than that reported in the 222 BCLC-C patients evaluated (20.6 versus 8.4 months; P < 0.0001) [39]. Taken together, these It is widely accepted that TACE promotes the synthesis of proangiogenic factors via a hypoxia-driven mechanism [35,40]. Therefore, there may be a rationale for the combination of sorafenib with TACE, since sorafenib inhibits the action of proangiogenic factors promoted by TACE [35,40,41].…”

Section: Radioembolizationmentioning

confidence: 73%

“…Taken together, these It is widely accepted that TACE promotes the synthesis of proangiogenic factors via a hypoxia-driven mechanism [35,40]. Therefore, there may be a rationale for the combination of sorafenib with TACE, since sorafenib inhibits the action of proangiogenic factors promoted by TACE [35,40,41]. Preliminary evidence, collected in a phase I trial, shows that the combination of sorafenib and TACE is not associated with major AEs and, therefore, could deserve further investigations [42].…”

Section: Radioembolizationmentioning

confidence: 93%

“…sorafenib in the treatment of the intermediate patient Sorafenib is currently the only drug approved for the treatment of patients with advanced HCC (BCLC-C stage); however, the use of this molecule in the treatment of intermediate patients is approved in patients with BCLC-B HCC who are unsuitable to TACE or in whom TACE resulted in unacceptable toxicity [1,22,[34][35][36]. According to available evidence, sorafenib has a role in patients who fail or are not eligible to TACE, as recently suggested by a Panel of Experts [22].…”

Section: Radioembolizationmentioning

confidence: 99%

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Intermediate hepatocellular carcinoma: current treatments and future perspectives

et al. 2013

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Current guidelines recommend transarterial chemoembolization (TACE) as the standard treatment of Barcelona-Clinic Liver Cancer (BCLC)-B patients. However, the long-term survival outcomes of patients managed with this technique do not appear fully satisfactory; in addition, intermediate-stage hepatocellular carcinoma (HCC) includes a heterogeneous population of patients with varying tumour burdens, liver function and disease aetiology. Therefore, not all patients with intermediate-stage HCC may derive similar benefit from TACE, and some patients may benefit from other treatment options, which are currently approved or being explored. These include different TACE modalities, such as selective TACE or drug-eluting beads TACE and radioembolization. The introduction of sorafenib in the therapeutic armamentarium for HCC has provided a new therapeutic option for the treatment of BCLC-B patients who are unsuitable to TACE or in whom TACE resulted in unacceptable toxicity. In addition, clinical trials aimed at investigating the potential role of this molecule in the treatment of patients with intermediate-stage HCC within combination therapeutic regimens are ongoing. This narrative review will present and discuss the most recent evidence on the locoregional or medical treatment with sorafenib in patients with intermediate-stage HCC.

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TACE with or without systemic therapy?

Cited by 22 publications

References 16 publications

EASL- and mRECIST-Evaluated Responses to Combination Therapy of Sorafenib with Transarterial Chemoembolization Predict Survival in Patients with Hepatocellular Carcinoma

EASL- and mRECIST-Evaluated Responses to Combination Therapy of Sorafenib with Transarterial Chemoembolization Predict Survival in Patients with Hepatocellular Carcinoma

Drug-Eluting Beads Loaded with Antiangiogenic Agents for Chemoembolization: In Vitro Sunitinib Loading and Release and In Vivo Pharmacokinetics in an Animal Model

Intermediate hepatocellular carcinoma: current treatments and future perspectives

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