BACKGROUND: Cholangiocarcinoma is a relatively rare invasive carcinoma that arises from the lining of the gallbladder and bile ducts and carries a very poor prognosis (Chabner BA et al. Harrison's manual of oncology. New York: McGraw-Hill; 2008). Its incidence in the US is on average one case per 100,000 persons per year and may be increasing in frequency (Darwin PE. Cholangiocarcinoma [Web page]. emedicine from WebMD, http://www.emedicine.com/med/TOPIC343.HTM , accessed July 22, 2008). Currently, the only treatment option that offers a potential for cure is radical surgical resection. Typically, only 30% of patients qualify for this, while, for the remainder, treatment is only palliative (Chabner BA et al. Harrison's manual of oncology. New York: McGraw-Hill; 2008). Sorafenib is an oral-targeted agent that acts as a multikinase inhibitor and competitively inhibits the Raf, vascular endothelial growth factor receptor 2 (VEGFR2), VEGFR3, platelet-derived growth factor receptor beta, Flt3, and C-KIT receptors (Chabner BA et al. Harrison's manual of oncology. New York: McGraw-Hill; 2008). It has demonstrated effective clinical antitumor activity in both renal cell and inoperable hepatocellular carcinoma gaining Food and Drug Administration approval for the latter carcinoma in November 2007. Its role in advanced cholangiocarcinoma is yet to be defined. METHODS: Two female patients with biopsy-proven multifocal moderately differentiated cholangiocarcinoma received single-agent sorafenib at standard doses. RESULTS: Both patients derived benefit in the form of disease stabilization with negligible cancer-related side effects lasting 4+ months. Sorafenib side effects were relatively modest aside for rash in one patient. CONCLUSIONS: Sorafenib use resulted in effective palliation in two patients with advanced cholangiocarcinoma. Larger phase 2 trials, will be necessary to confirm this initial observation.
BACKGROUND:Cholangiocarcinoma is a relatively rare invasive carcinoma that arises from the lining of the gallbladder and bile ducts and carries a very poor prognosis (Chabner BA et al. Harrison's manual of oncology. New York: McGraw-Hill; 2008). Its incidence in the US is on average one case per 100,000 persons per year and may be increasing in frequency (Darwin PE. Cholangiocarcinoma [Web page]. emedicine from WebMD, http://www.emedicine.com/med/TOPIC343.HTM , accessed July 22, 2008). Currently, the only treatment option that offers a potential for cure is radical surgical resection. Typically, only 30% of patients qualify for this, while, for the remainder, treatment is only palliative (Chabner BA et al. Harrison's manual of oncology. New York: McGraw-Hill; 2008). Sorafenib is an oral-targeted agent that acts as a multikinase inhibitor and competitively inhibits the Raf, vascular endothelial growth factor receptor 2 (VEGFR2), VEGFR3, platelet-derived growth factor receptor beta, Flt3, and C-KIT receptors (Chabner BA et al. Harrison's manual of oncology. New York: McGraw-Hill; 2008). It has demonstrated effective clinical antitumor activity in both renal cell and inoperable hepatocellular carcinoma gaining Food and Drug Administration approval for the latter carcinoma in November 2007. Its role in advanced cholangiocarcinoma is yet to be defined. METHODS: Two female patients with biopsy-proven multifocal moderately differentiated cholangiocarcinoma received single-agent sorafenib at standard doses. RESULTS: Both patients derived benefit in the form of disease stabilization with negligible cancer-related side effects lasting 4+ months. Sorafenib side effects were relatively modest aside for rash in one patient. CONCLUSIONS:Sorafenib use resulted in effective palliation in two patients with advanced cholangiocarcinoma. Larger phase 2 trials, will be necessary to confirm this initial observation.
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Authors: Elena V Poddubskaya; Madina P Baranova; Daria O Allina; Philipp Y Smirnov; Eugene A Albert; Alexey P Kirilchev; Alexey A Aleshin; Marina I Sekacheva; Maria V Suntsova Journal: Exp Hematol Oncol Date: 2018-09-06