TY - JOUR
T1 - Psychotic disorder induced by a combination of sorafenib and BAY86-9766
AU - Kuo, Yen Lin
AU - Yang, Yen Kuang
AU - Cheng, Hsiu Chi
AU - Yen, Chia Jui
AU - Chen, Po See
PY - 2014/7
Y1 - 2014/7
N2 - The Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK cascade is important in the intra-cellular transduction of neurotransmitters, such as dopamine and glutamate. Sorafenib (Nexavar), a multi-kinase inhibitor targeting Raf kinase, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor, has shown promising results in the treatment of malignancies. BAY86-9766, a novel selective MEK 1/2 inhibitor, is being evaluated in clinical trials as an anticancer drug. We describe herein a hepatocellular carcinoma patient presenting with recurrent psychotic symptoms in the course of the BASIL trial (assessing BAY86-9766 plus sorafenib for the treatment of liver cancer). In this case, VEGFR inhibition caused by sorafenib alone may have contributed to the development of psychosis. A change in ERK activity might also have been involved. However, whether single or combination use of the two drugs is responsible for inducing the psychotic symptoms remains unclear. In summary, the role of the ERK pathway in psychosis is still vague. Further investigation of the ERK activity in patients with psychotic disorders may disclose its role in the pathophysiology of psychosis.
AB - The Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK cascade is important in the intra-cellular transduction of neurotransmitters, such as dopamine and glutamate. Sorafenib (Nexavar), a multi-kinase inhibitor targeting Raf kinase, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor, has shown promising results in the treatment of malignancies. BAY86-9766, a novel selective MEK 1/2 inhibitor, is being evaluated in clinical trials as an anticancer drug. We describe herein a hepatocellular carcinoma patient presenting with recurrent psychotic symptoms in the course of the BASIL trial (assessing BAY86-9766 plus sorafenib for the treatment of liver cancer). In this case, VEGFR inhibition caused by sorafenib alone may have contributed to the development of psychosis. A change in ERK activity might also have been involved. However, whether single or combination use of the two drugs is responsible for inducing the psychotic symptoms remains unclear. In summary, the role of the ERK pathway in psychosis is still vague. Further investigation of the ERK activity in patients with psychotic disorders may disclose its role in the pathophysiology of psychosis.
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U2 - 10.1016/j.genhosppsych.2012.03.001
DO - 10.1016/j.genhosppsych.2012.03.001
M3 - Article
C2 - 24773940
AN - SCOPUS:84902651285
VL - 36
SP - 450.e5-450.e7
JO - General Hospital Psychiatry
JF - General Hospital Psychiatry
SN - 0163-8343
IS - 4
ER -