Safety and efficacy of sorafenib in hepatocellular carcinoma: the impact of the Child-Pugh score

Hollebecque, Antoine; Cattan, Stéphane; Romano, O.; Sergent, Géraldine; Mourad, Abbas; Louvet, Alexandre; Dharancy, Sébastien; Boleslawski, Emmanuel; Truant, Stéphanie; Pruvot, François‐René; Hebbar, Mohamed; Ernst, Olivier; Mathurin, Philippe

doi:10.1111/j.1365-2036.2011.04860.x

Cited by 108 publications

(108 citation statements)

References 29 publications

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“…Therefore, it is important to establish predictive factors for sorafenib therapy. Previous studies demonstrated that several factors, such as Eastern Cooperative Oncology Group PS and CP class A status were predictive factors for patients with HCC receiving sorafenib therapy (11,12). In recent reports, skeletal muscle mass loss was found to be significantly associated with malnutrition and poor liver function (13,14).…”

Section: Discussionmentioning

confidence: 99%

Significance of psoas muscle thickness as an indicator of muscle atrophy in patients with hepatocellular carcinoma treated with sorafenib

Yamashima

Miyaaki

Honda

et al. 2017

Molecular and Clinical Oncology

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Abstract. Sarcopenia has been reported to be associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma (HCC). The aim of the present study was to determine whether sarcopenia was associated with the prognosis of patients with HCC treated with sorafenib. A total of 40 patients with HCC who were treated with sorafenib were evaluated. As an indicator of skeletal muscle mass, transverse psoas muscle thickness (TPMT) was measured on computed tomography images at the level of the umbilicus prior to treatment initiation and after 1-3 months of treatment. Pre-TPMT/height was not associated with progression-free survival (PFS) or overall survival (OS). The change in TPMT/height prior to and following treatment was also not associated with PFS; however, the change of TPMT/height was an independent factor affecting OS (P=0.020). A total of 40 patients were divided into two groups depending on the degree of TPMT/height loss (mild and severe muscle atrophy groups). Patients with mild muscle atrophy exhibited a significantly longer OS compared with patients with severe muscle atrophy (P=0.045). Thus, the change in skeletal muscle thickness calculated as TPMT/height may be a simple predictor of survival for patients with HCC treated with sorafenib.

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Section: Discussionmentioning

confidence: 99%

Significance of psoas muscle thickness as an indicator of muscle atrophy in patients with hepatocellular carcinoma treated with sorafenib

Yamashima

Miyaaki

Honda

et al. 2017

Molecular and Clinical Oncology

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“…An additional finding was the 8.1-month median OS of the five Child-Pugh B patients. Previous experience with comparable patient populations has shown an OS for Child Pugh B patients in the range of 3.5-5.5 months [1][2][3]. Considering that Child Pugh B patients treated with sorafenib generally have poor outcomes due to underlying liver dysfunction, CF102 also may be considered as a drug to be developed for this patient sub-population.…”

Section: Discussionmentioning

confidence: 99%

CF102 for the Treatment of Hepatocellular Carcinoma: A Phase I/II, Open-Label, Dose-Escalation Study

et al. 2012

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Background. The A 3 adenosine receptor (A 3 AR) is overexpressed in the tumor and in the peripheral blood mononuclear cells of patients with hepatocellular carcinoma (HCC). The orally active drug candidate CF102, an A 3 AR agonist, induces apoptosis of HCC cells via deregulation of the Wnt signaling pathway. In this open label phase I/II trial, the safety and clinical effects of CF102 were assessed in patients with advanced unresectable HCC.Methods. The primary objectives of this trial were to examine the safety and pharmacokinetic (PK) behavior of CF102 given orally (1, 5, and 25 mg BID) in 28-day cycles. Evaluation of anti-tumor effects and the utilization of A 3 AR as a biological predictive marker of response to CF102 were the secondary objectives.Results. Eighteen patients received CF102-six at each dose level. No serious drug-related adverse events or doselimiting toxicities were observed. CF102 demonstrated good oral bioavailability and linear PK behavior. Median overall survival in the study population, 67% of whom had received prior sorafenib, was 7.8 months, and for Child Pugh B patients (28%) it was 8.1 months. Stable disease by RECIST was observed in four patients for at least 4 months. CF102 maintained liver function over a 6-month period. A correlation between receptor overexpression levels at baseline and patients' overall survival was found. One of the patients who presented with skin nodules that were biopsy-proven to be HCC metastases prior to the trial showed complete metastasis regression during three months of treatment with CF102.

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“…The median OS for Child-Pugh A patients was 41 weeks and for Child-Pugh B patients 14 weeks (7). Several studies also demonstrated that Child-Pugh B patients fare worse compared with Child-Pugh A patients and also present with worsening of cirrhosis more frequently during treatment (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma

Fonseca

Barroso‐Sousa

Bento

et al. 2015

Molecular and Clinical Oncology

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Abstract. Sorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval ( CI): 0.33-5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22-13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and α-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction.

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Safety and efficacy of sorafenib in hepatocellular carcinoma: the impact of the Child-Pugh score

Abstract: SUMMARY BackgroundSorafenib increases median survival and time to radiological progression in patients with advanced hepatocellular carcinoma, but its benefit for ChildPugh B patients remains uncertain.

Cited by 108 publications

References 29 publications

Significance of psoas muscle thickness as an indicator of muscle atrophy in patients with hepatocellular carcinoma treated with sorafenib

Significance of psoas muscle thickness as an indicator of muscle atrophy in patients with hepatocellular carcinoma treated with sorafenib

CF102 for the Treatment of Hepatocellular Carcinoma: A Phase I/II, Open-Label, Dose-Escalation Study

Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma

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