J Howell1,2,3, D J Pinato1, R Ramaswami1, D Bettinger4, T Arizumi5, C Ferrari6, C Yen1, A Gibbin6, M E Burlone6, G Guaschino6, L Sellers1, J Black1, M Pirisi5, M Kudo5, R Thimme4, J-W Park7, R Sharma1. 1. Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK. 2. Department of Medicine, University of Melbourne, St Vincent's Hospital, Melbourne, Vic., Australia. 3. Centre for Population Health, Macfarlane-Burnet Institute, Melbourne, Vic., Australia. 4. Department of Medicine II, University Hospital Freiburg, Freiburg, Germany. 5. Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka-Sayama, Osaka, Japan. 6. Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro", Novara, Italy. 7. Center for Liver Cancer, National Cancer Center, Goyang, Gyeonggi, South Korea.
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.
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 sorafenibtoxicity 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 sorafenibtoxicity 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.
Authors: Samantha Armstrong; Tina Roy; Bhavana Singh; Monika Kulasekaran; Fatima Shaukat; Xue Geng; Hongkun Wang; Petra Prins; Reena C Jha; Marion L Hartley; Aiwu Ruth He Journal: J Cancer Res Clin Oncol Date: 2022-06-30 Impact factor: 4.553
Authors: Dominik Bettinger; David J Pinato; Michael Schultheiss; Rohini Sharma; Lorenza Rimassa; Tiziana Pressiani; Michela E Burlone; Mario Pirisi; Masatoshi Kudo; Joong Won Park; Nico Buettner; Christoph Neumann-Haefelin; Tobias Boettler; Nasrin Abbasi-Senger; Horst Alheit; Wolfgang Baus; Oliver Blanck; Sabine Gerum; Mathias Guckenberger; Daniel Habermehl; Christian Ostheimer; Oliver Riesterer; Jörg Tamihardja; Anca-Ligia Grosu; Robert Thimme; Thomas Baptist Brunner; Eleni Gkika Journal: Liver Cancer Date: 2018-07-12 Impact factor: 11.740
Authors: Giorgia Marisi; Alessandro Cucchetti; Paola Ulivi; Matteo Canale; Giuseppe Cabibbo; Leonardo Solaini; Francesco G Foschi; Serena De Matteis; Giorgio Ercolani; Martina Valgiusti; Giovanni L Frassineti; Mario Scartozzi; Andrea Casadei Gardini Journal: World J Gastroenterol Date: 2018-09-28 Impact factor: 5.742