Unresectable, Recurrent, or Metastatic Gallbladder Cancer
These patients are not curable. Significant symptomatic benefit can often be achieved with relief of biliary obstruction. A few patients have very slow-growing tumors and may live several years. Patients with unresectable, recurrent, or metastatic gallbladder 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. The preferred approach is percutaneous transhepatic drainage or endoscopically placed stents; surgical bypass may be appropriate when these approaches are infeasible.
Palliative radiation therapy after biliary drainage 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.
- 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 gallbladder cancer 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 149 patients with gallbladder cancer. Grade 3 and 4 toxicities occurred with similar frequency in both study arms, with the exception of increased hematologic toxic effects in patients randomly assigned to gemcitabine-cisplatin and increased hepatotoxicity in patients randomly assigned to single-agent gemcitabine.
A multi-institutional, randomized, phase III study (NCT01149122) of advanced biliary cancers that evaluated the benefit of chemotherapy (gemcitabine and oxaliplatin) with or without erlotinib failed to meet its endpoint of improvement in OS and progression-free survival.[Level of evidence: 1iiD]
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 gallbladder cancer, recurrent gallbladder cancer and metastatic gallbladder 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.
- Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001. [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]
- Lee J, Park SH, Chang HM, et al.: Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 13 (2): 181-8, 2012. [PUBMED Abstract]