Objective: The aim of this study was to evaluate the efficacy and safety of single-agent S-1 in patients with advanced biliary tract cancer. Methods: S-1 was administered orally at a dose of 80 mg/m² for 28 days, followed by 14 days of rest (1 cycle); treatment was repeated until disease progression, unacceptable toxicity, or patient refusal. Results: Forty-five patients were enrolled between January 2005 and June 2008. Among these, 29 patients received S-1 as first-line chemotherapy and 16 patients received S-1 as second-line chemotherapy. The response rates for first- and second-line chemotherapy were 17.2 and 18.8%, respectively. The median times to progression for the first- and second-line chemotherapy groups were 4.2 and 5.5 months (p = 0.91), respectively. The median overall survival and 1-year survival rate for each group were 8.7 and 8.0 months and 42.2 and 38.2%, respectively (p = 0.62). Only the first-line chemotherapy group experienced grade 3/4 toxicities, including leukopenia (6.9%), neutropenia (10.3%), anemia (6.9%), thrombocytopenia (10.3%) and total bilirubin elevation (3.4%). Conclusion: S-1 monotherapy is a feasible and moderately efficacious treatment for advanced biliary tract cancer, as a first- or second-line chemotherapy regimen.

Biliary tract cancer refers to a group of malignancies including cholangiocarcinoma, gallbladder cancer, and ampullary cancer. While surgical resection is considered the only curative treatment, postoperative recurrence can sometimes occur. Adjuvant chemotherapy is used to prolong prognosis in some cases. Many unresectable cases are also treated with chemotherapy. Therefore, systemic chemotherapy is widely introduced for the treatment of biliary tract cancer. Evidence on chemotherapy for biliary tract cancer is recently on the increase. Combination chemotherapy with gemcitabine and cisplatin is currently the standard of care for first-line chemotherapy in advanced cases. Recently, FOLFOX also demonstrated efficacy as a second-line treatment. In addition, efficacies of isocitrate dehydrogenase inhibitors and fibroblast growth factor receptor inhibitors have been shown. In the adjuvant setting, capecitabine monotherapy has become the standard of care in Western countries. In addition to conventional cytotoxic agents, molecular-targeted agents and immunotherapy have been evaluated in multiple clinical trials. Genetic testing is used to check for genetic alterations and molecular-targeted agents and immunotherapy are introduced based on tumor characteristics. In this article, we review the latest evidence of chemotherapy for biliary tract cancer.

Hereditary pancreatic cancers are caused by several inherited genes. Familial pancreatic cancer is defined as pancreatic cancer arising in a patient with at least two first-degree relatives with pancreatic cancer in the absence of an identified genetic cause. Hereditary pancreatic cancer syndromes and familial pancreatic cancers account for about 10% of pancreatic cancer cases. Germline mutations in BRCA1, BRCA2, ATM, PALB2, CDKN2A, STK11, and TP53 and mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) are among the well-known inherited susceptibility genes. Currently available targeted medications include poly (ADP-ribose) polymerase inhibitors (PARP) for cases with mutant BRCA and immune checkpoint inhibitors for cases with mismatch repair deficiency. Loss of heterozygosity of hereditary pancreatic cancer susceptibility genes such as BRCA1/2 plays a key role in carcinogenesis and sensitivity to PARP inhibitors. Signature 3 identified by whole genome sequencing is also associated with homologous recombination deficiency and sensitivity to targeted therapies. In this review, we summarize molecular features and treatments of hereditary pancreatic cancer syndromes and surveillance procedures for unaffected high-risk cases. We also review transgenic murine models to gain a better understanding of carcinogenesis in hereditary pancreatic cancer.