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On-target sorafenib toxicity predicts improved survival in hepatocellular carcinoma: a multi-centre, prospective study

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Title: On-target sorafenib toxicity predicts improved survival in hepatocellular carcinoma: a multi-centre, prospective study
Authors: Howell, J
Pinato, DJ
Ramaswami, R
Bettinger, D
Arizumi, T
Ferrari, C
Yen, C
Gibbin, A
Burlone, ME
Guaschino, G
Sellers, L
Black, J
Pirisi, M
Kudo, M
Thimme, R
Park, J-W
Sharma, R
Item Type: Journal Article
Abstract: Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and has high mortality despite treatment. While sorafenib has a survival benefit for patients with advanced HCC, clinical response is highly variable. Aim: To determine whether development of sorafenib toxicity is a prognostic marker of survival in HCC. Methods: In this prospective multicentre cohort study, patients with advanced-stage HCC receiving sorafenib were recruited from five international specialist centres. Demographic and clinical data including development and grade of sorafenib toxicity during treatment, radiological response to sorafenib and survival time (months) were recorded prospectively. Results: A total of 634 patients with advanced-stage HCC receiving sorafenib were recruited to the study, with a median follow-up of 6692.3 person-months at risk. The majority of patients were male (81%) with Child–Pugh A stage liver disease (74%) and Barcelona Clinic Liver Cancer stage C HCC (64%). Median survival time was 8.1 months (IQR 3.8–18.6 months). 94% experienced at least one sorafenib-related toxicity: 34% diarrhoea, 16% hypertension and 37% hand-foot syndrome (HFS). Twenty-one per cent ceased sorafenib due to toxicity and 59% ceased treatment due to progressive disease or death. On multivariate analysis, sorafenib-related diarrhoea (HR 0.76, 95% CI 0.61–0.95, P = 0.017), hypertension (HR 0.531, 95% CI 0.37–0.76, P < 0.0001) and HFS (HR 0.65, 95% CI 0.51–0.81, P < 0.0001) were all significant independent predictors of overall survival after adjusting for age, severity of liver disease, tumour stage and sorafenib dose. Conclusion: Development of sorafenib-related toxicity including diarrhoea, hypertension and hand-foot syndrome is associated with prolonged overall survival in patients with advanced-stage HCC on sorafenib.
Issue Date: 2-Mar-2017
Date of Acceptance: 17-Jan-2017
URI: http://hdl.handle.net/10044/1/47864
DOI: https://dx.doi.org/10.1111/apt.13977
ISSN: 0269-2813
Publisher: WILEY
Start Page: 1146
End Page: 1155
Journal / Book Title: ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Volume: 45
Issue: 8
Copyright Statement: © 2017 John Wiley & Sons Ltd. This is the accepted version of the following article: Howell, J., Pinato, D. J., Ramaswami, R., Bettinger, D., Arizumi, T., Ferrari, C., Yen, C., Gibbin, A., Burlone, M. E., Guaschino, G., Sellers, L., Black, J., Pirisi, M., Kudo, M., Thimme, R., Park, J.-W. and Sharma, R. (2017), On-target sorafenib toxicity predicts improved survival in hepatocellular carcinoma: a multi-centre, prospective study. Aliment Pharmacol Ther, 45: 1146–1155. doi:10.1111/apt.13977, which has been published in final form at https://dx.doi.org/10.1111/apt.13977
Sponsor/Funder: The Academy of Medical Sciences
Funder's Grant Number: N/A
Keywords: Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
Pharmacology & Pharmacy
TYROSINE KINASE INHIBITORS
CHILD-PUGH SCORE
PROGNOSTIC-FACTORS
SKIN TOXICITY
PHASE-II
CIRRHOSIS
EFFICACY
LIVER
MICROBIOME
OUTCOMES
1103 Clinical Sciences
1115 Pharmacology And Pharmaceutical Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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