Abstract
It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective against biliary tract cancer. Although some targeted agents have been investigated as monotherapy for first-line chemotherapy, none were found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen and have been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogeneous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy, and international collaboration is important.
Highlights
Biliary tract cancer is rather common in Latin America and Asia, including Japan, while being relatively rare in European countries and the United States; approximately 16,000 patients in Japan and5,000 patients in the United States are newly diagnosed as having this cancer each year [1,2,3]
The survival in patients with unresectable biliary tract cancer has been shown to differ by the tumor type, that is, gallbladder carcinoma, intrahepatic cholangiocarcinoma, or extrahepatic cholangiocarcinoma
This study revealed that the absence of KRAS mutation and presence of epidermal growth factor receptor (EGFR) amplification may be potentially predictive molecular markers of the sensitivity of cholangiocarcinoma to EGFR-targeted therapy [32]
Summary
Biliary tract cancer is rather common in Latin America and Asia, including Japan, while being relatively rare in European countries and the United States; approximately 16,000 patients in Japan and. The survival in patients with unresectable biliary tract cancer has been shown to differ by the tumor type, that is, gallbladder carcinoma, intrahepatic cholangiocarcinoma, or extrahepatic cholangiocarcinoma. It would, be ideal to conduct separate clinical trials in each cancer. Despite the numerous phase II studies conducted of treatments for advanced biliary tract cancer, no accepted standard treatment for this tumor type has been established yet, because of the low incidence and small number of patients and the lack of adequately powered randomized controlled trials. The combination of gemcitabine plus a platinum agent (cisplatin or oxaliplatin) has come to be recognized as standard therapy for unresectable biliary tract cancer. The results of preclinical experiments and clinical trials of molecular targeted therapy for the treatment of biliary tract cancer are reviewed, and the possibilities and future directions of the use of targeted agents are discussed
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