TY - JOUR
T1 - Sorafenib in the treatment of hepatocellular carcinoma
T2 - A multi-centre real-world study
AU - Doyle, Adam
AU - Marsh, Philip
AU - Gill, Raghubinder
AU - Rodov, Marcia
AU - Mohsen, Waled
AU - Varma, Poornima
AU - Hong, Thai
AU - Strasser, Simone I
AU - Bell, Sally
AU - Ryan, Marno
AU - Nicoll, Amanda
AU - Lubel, John
AU - Gow, Paul J.
AU - Fink, Michael Anthony
AU - Roberts, Stuart
AU - Kemp, William
AU - Kronborg, Ian
AU - Arachchi, Niranjan
AU - Knight, Virginia
AU - Dev, Anouk
PY - 2016/8/2
Y1 - 2016/8/2
N2 - Objective: Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. Material and methods: Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. Results: Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2–3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2–3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). Conclusions: Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.
AB - Objective: Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. Material and methods: Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. Results: Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2–3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2–3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). Conclusions: Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.
KW - Adverse effects
KW - multivariate analysis
KW - progression
KW - survival
UR - http://www.scopus.com/inward/record.url?scp=84966701408&partnerID=8YFLogxK
U2 - 10.3109/00365521.2016.1166518
DO - 10.3109/00365521.2016.1166518
M3 - Article
C2 - 27161568
AN - SCOPUS:84966701408
SN - 0036-5521
VL - 51
SP - 979
EP - 985
JO - Scandinavian Journal of Gastroenterology
JF - Scandinavian Journal of Gastroenterology
IS - 8
ER -