Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stool or dark urine may also occur. Other biliary tract cancers include gallbladder cancer and cancer of the ampulla of Vater.Risk factors for cholangiocarcinoma include primary sclerosing cholangitis (an inflammatory disease of the bile ducts), ulcerative colitis, cirrhosis, hepatitis C, hepatitis B, infection with certain liver flukes, and some congenital liver malformations. However, most people have no identifiable risk factors. The diagnosis is suspected based on a combination of blood tests, medical imaging, endoscopy, and sometimes surgical exploration. The disease is confirmed by examination of cells from the tumor under a microscope. It is typically an adenocarcinoma (a cancer that forms glands or secretes mucin).Cholangiocarcinoma is typically incurable at diagnosis which is why early detection is ideal. In these cases palliative treatments may include surgical resection, chemotherapy, radiation therapy, and stenting procedures. In about a third of cases involving the common bile duct and less commonly with other locations the tumor can be completely removed by surgery offering a chance of a cure. Even when surgical removal is successful chemotherapy and radiation therapy are generally recommended. In certain cases surgery may include a liver transplantation. Even when surgery is successful the 5-year survival is typically less than 50%.Cholangiocarcinoma is rare in the Western world, with estimates of it occurring in 0.5–2 people per 100,000 per year.
The U.S. Food and Drug Administration rejected the application for marketing approval in 2012, on the basis that the clinical trial did not show efficacy based on a functional endpoint, and requested further clinical trials. In May 2019, the FDA approved two tafamidis preparations, Vyndaqel (tafamidis meglumine) and Vyndamax (tafamidis), for the treatment of transthyretin-mediated cardiomyopathy. The drug was approved in Japan in 2013; regulators there made the approval dependent on further clinical trials showing better evidence of efficacy.The FDA approved tafamidis meglumine based primarily on evidence from a clinical trial of 441 adult patients conducted at 60 sites in Belgium, Brazil, Canada, Czech Republic, Spain, France, Greece, Italy, Japan, Netherlands, Sweden, Great Britain, and the United States.There was one trial that evaluated the benefits and side effects of tafamidis for the treatment of transthyretin amyloidosis with cardiomyopathy, in which patients were randomly assigned to receive either tafamidis (either 20 or 80 mg) or placebo for 30 months. About 90% of patients in the trial were taking other drugs for heart failure (consistent with the standard of care).The European Medicines Agency designated tafamidis an orphan medicine and the Food and Drug Administration designated tafamidis meglumine an orphan drug. Society and culture
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Tafamidis was approved in the European Union in 2011 for the treatment of transthyretin amyloidosis with polyneuropathy, and in Japan in 2013.