Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib

Pinter, Matthias; Sieghart, Wolfgang; Hucke, Florian; Graziadei, Ivo; Vogel, Wolfgang; Maieron, A; Königsberg, Robert; Weissmann, A; Kornek, Gabriela; Matejka, J.; Stauber, Rudolf; Buder, R; Grünberger, Birgit; Schöniger–Hekele, Maximilian; Muller, Cyril; Peck‐Radosavljevic, Markus

doi:10.1111/j.1365-2036.2011.04823.x

Cited by 70 publications

(67 citation statements)

References 31 publications

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“…Prior the second TACE, most patients had Child-Pugh A cirrhosis (n ¼ 69, 62%). Overall, the median number of TACE interventions was 3 (range [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The median time interval between the first and second TACE was 42 days (range 26-85).…”

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confidence: 99%

“…As most patients with HCC also suffer from liver cirrhosis, not only tumor characteristics but also the degree of liver dysfunction are of prognostic importance for patients undergoing TACE. Several studies showed 8 that baseline tumor characteristics like tumor size or extent, alpha-fetoprotein (AFP) values, as well as baseline Child-Pugh score, presence of ascites, and several baseline lab values, e.g., AST 9 are associated with OS of HCC patients.…”

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confidence: 99%

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The ART of decision making: Retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma

et al. 2013

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We aimed to establish an objective point score to guide the decision for retreatment with transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). In all, 222 patients diagnosed with HCC and treated with multiple TACE cycles between January 1999 and December 2009 at the Departments of Gastroenterology/Hepatology of the Medical Universities of Vienna (training cohort) and Innsbruck (validation cohort) were included. We investigated the effect of the first TACE on parameters of liver function and tumor response and their impact on overall survival (OS, log rank test) and developed a point score (ART score: Assessment for Retreatment with TACE) in the training cohort (n 5 107, Vienna) by using a stepwise Cox regression model. The ART score was externally validated in an independent validation cohort (n 5 115, Innsbruck). The increase of aspartate aminotransferase (AST) by >25% (hazard ratio [HR] 8.4; P < 0.001), an increase of Child-Pugh score of 1 (HR 2.0) or !2 points (HR 4.4) (P < 0.001) from baseline, and the absence of radiologic tumor response (HR 1.7; P 5 0.026) remained independent negative prognostic factors for OS and were used to create the ART score. The ART score differentiated two groups (0-1.5 points; !2.5 points) with distinct prognosis (median OS: 23.7 versus 6.6 months; P < 0.001) and a higher ART score was associated with major adverse events after the second TACE (P 5 0.011). These results were confirmed in the external validation cohort and remained significant irrespective of ChildPugh stage and the presence of ascites prior the second TACE. Conclusion: An ART score of !2.5 prior the second TACE identifies patients with a dismal prognosis who may not profit from further TACE sessions. (HEPATOLOGY 2013;57:2261-2273

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

The ART of decision making: Retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma

et al. 2013

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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.…”

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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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“…7,8 Furthermore, in Child-Pugh B patients, baseline aspartate aminotransferase has been proposed to predict for patients more likely to benefit from sorafenib. 9 To date, no molecular predictive biomarker for sorafenib response in HCC treatment has been validated and accepted in clinical practice. Efforts in such a direction were performed during the SHARP molecular biomarker program, but were of limited success.…”

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confidence: 99%

A needle in a haystack: Identifying biomarkers to personalize systemic therapy in patients with hepatocellular carcinoma

Wege

Brümmendorf²,

Gambacorti‐Passerini

2013

Hepatology

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Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib

Abstract: SUMMARY BackgroundSorafenib is the new reference standard for patients with advanced hepatocellular carcinoma (HCC).

Cited by 70 publications

References 31 publications

The ART of decision making: Retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma

The ART of decision making: Retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma

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

A needle in a haystack: Identifying biomarkers to personalize systemic therapy in patients with hepatocellular carcinoma

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