In December 2009 he experienced an episode of mild epistaxis secondary to thrombocytopenia, requiring the cessation of the drug for a period of 7 days. It was resumed at a lower dose of 200 mg twice a day. Attempts to increase the drug dosage have resulted in recurrent thrombocytopenia and the patient has remained on 200 mg twice a day since June 2011. The patient’s disease has now remained stable for 44 months, far exceeding any reports that we were able to find in the current literature.
#selleck inhibitor keyword# Discussion Sorafenib is a small molecule that inhibits tumor-cell proliferation and tumor angiogenesis and increases the rate of apoptosis in a wide range of tumor models. It acts by inhibiting the serine-threonine kinases Raf-1 and B-Raf and the receptor tyrosine kinase activity of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3 and platelet-derived
growth factor receptor β (PDGFR-β) (6). In cholangiocarcinoma cells, it interferes with the STAT3 signaling pathway, reduces cellular expression Inhibitors,research,lifescience,medical of Mcl-1 and sensitizes cells to TRAIL mediated apoptosis (7). It may also work by inhibiting the VEGF stimulation produced by the cholangiocytes (8). Sorafenib has not gained FDA approval for use in advanced cholangiocarcinoma. Despite showing some early Inhibitors,research,lifescience,medical promise (9), results of http://www.selleckchem.com/products/ganetespib-sta-9090.html trials using Sorafenib Inhibitors,research,lifescience,medical have been rather disappointing with response rates and median overall survival similar to commonly used chemotherapeutic agents. A phase II trial using Sorafenib as a single agent in advanced cholangiocarcinoma and gall bladder cancer failed to demonstrate a clinically significant objective response, but did show a positive impact on survival that is comparable to most active chemotherapy agents (4). A more recent trial reported a progression free survival of 2.3 months, with median overall survival of 4.4 months (10). The role of Sorafenib in cholangiocarcinoma remains uncertain. There is an ongoing trial evaluating its potential benefit when combined with gemcitabine and Inhibitors,research,lifescience,medical oxaliplatin in patients
Carfilzomib with advanced cholangiocarcinoma. Our patient has derived a very impressive benefit from the drug with a progression-free-survival approaching 4 years. The side effect profile has been very manageable and he has maintained an excellent quality of life. We hope our patient provides promise that in the future we may be able to selectively identify individuals that may derive a similar benefit. Acknowledgements Disclosure: The authors declare no conflict of interest.
Pancreatic cancer is the fifth leading cause of cancer mortality in the United States. In 2011, there were an estimated 44,030 new cases and 37,660 deaths (1). Curative therapy for patients with nonmetastatic disease necessarily includes extirpative surgery.