Unresectable, Recurrent, or Metastatic Extrahepatic Bile Duct Cancer
Patients with unresectable extrahepatic bile duct cancer have cancer that cannot be completely removed by the surgeon. These patients represent the majority of cases of bile duct cancer. Often a proximal bile duct cancer invades directly into the adjacent liver or into the hepatic artery or portal vein. Portal hypertension may result. Spread to distant parts of the body is uncommon, though transperitoneal and hematogenous hepatic metastases do occur with bile duct cancers of all sites. Invasion along the biliary tree and into the liver is common. Moreover, the majority of patients who undergo resection will develop recurrent disease within the hepatobiliary system or less frequently at distant sites.
Patients with unresectable, recurrent, or metastatic extrahepatic bile duct cancer should be considered for inclusion in clinical trials whenever possible. Information about ongoing clinical trials is available from the NCI Web site.
- Relief of biliary obstruction is warranted when symptoms such as pruritus and hepatic dysfunction outweigh other symptoms from the cancer. When possible, such palliation can be achieved by anastomosis of the bile duct to the bowel or by the placement of bile duct stents by operative, endoscopic, or percutaneous techniques.[1,2]
Palliative radiation therapy after biliary bypass or intubation may be beneficial, and patients may be candidates for inclusion in clinical trials that explore ways to improve the effects of radiation therapy with various radiation sensitizers, such as hyperthermia, radiosensitizer drugs, or cytotoxic chemotherapeutic agents. If a percutaneous catheter has been placed, it can be used as a conduit for placement of sources for brachytherapy.[3,4] Information about ongoing clinical trials is available from the NCI Web site.
- Systemic chemotherapy is appropriate for selected patients with adequate performance status and intact organ function. Fluoropyrimidines, gemcitabine, platinum agents, and docetaxel have been reported to produce transient partial remissions in a minority of patients.
A randomized, phase III study of up to 6 months of gemcitabine versus gemcitabine and cisplatin in 410 patients with unresectable, recurrent, or metastatic biliary tract carcinoma demonstrated an improvement in median overall survival (OS) among patients treated with combination therapy (11.7 months vs. 8.1 months; HR, 0.64; (95% confidence interval, 0.52–0.80); P < .001.[Level of evidence: 1iiA] A similar median OS benefit was demonstrated in all subgroups, including 73 patients with extrahepatic bile duct cancer and 57 patients with hilar tumors. Grade 3 and 4 toxicities occurred with similar frequency in both study arms, with the exception of increased hematologic toxicity in patients randomly assigned to gemcitabine-cisplatin and increased hepatotoxicity in patients randomly assigned to single-agent gemcitabine.
Other drugs and drug combinations await evaluation in randomized trials.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with unresectable extrahepatic bile duct cancer, recurrent extrahepatic bile duct cancer and metastatic extrahepatic bile duct cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Nordback IH, Pitt HA, Coleman J, et al.: Unresectable hilar cholangiocarcinoma: percutaneous versus operative palliation. Surgery 115 (5): 597-603, 1994. [PUBMED Abstract]
- Levy MJ, Baron TH, Gostout CJ, et al.: Palliation of malignant extrahepatic biliary obstruction with plastic versus expandable metal stents: An evidence-based approach. Clin Gastroenterol Hepatol 2 (4): 273-85, 2004. [PUBMED Abstract]
- Fritz P, Brambs HJ, Schraube P, et al.: Combined external beam radiotherapy and intraluminal high dose rate brachytherapy on bile duct carcinomas. Int J Radiat Oncol Biol Phys 29 (4): 855-61, 1994. [PUBMED Abstract]
- Shin HS, Seong J, Kim WC, et al.: Combination of external beam irradiation and high-dose-rate intraluminal brachytherapy for inoperable carcinoma of the extrahepatic bile ducts. Int J Radiat Oncol Biol Phys 57 (1): 105-12, 2003. [PUBMED Abstract]
- Valle J, Wasan H, Palmer DH, et al.: Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362 (14): 1273-81, 2010. [PUBMED Abstract]