Bile duct cancer is mostly seen in middle-aged and elderly men aged 50-70 years old, and most of them are highly, moderately or poorly differentiated adenocarcinomas, with few other tissue types. Cholangiocarcinoma has a complex etiology, insidious onset and atypical symptoms, and most patients are already in advanced local stage or have distant metastasis when diagnosed. Its malignancy is high, treatment is difficult and prognosis is very poor. More than 80% of patients die within one year after diagnosis, and the 5-year survival rate is only about 5%. Surgery is the only treatment that can cure bile duct cancer radically, but it is important to consider whether the tumor invades the surrounding blood vessels and lymphatic vessels; in fact, only about 10% of early stage patients can receive radical surgical resection. Meanwhile, because of the limited role of radiotherapy in advanced cholangiocarcinoma, palliative chemotherapy is the main treatment modality for locally advanced cholangiocarcinoma that is inoperable or accompanied by distant metastases. However, cholangiocarcinoma is not sensitive to chemotherapy and is less sensitive than other gastrointestinal tract tumors. However, if administered appropriately, chemotherapy can help relieve symptoms caused by the tumor (such as jaundice and pain) and improve the patient’s quality of life, thus prolonging survival. Currently, the first-line chemotherapeutic options for advanced cholangiocarcinoma include the following: I. Single-agent chemotherapy (1) Fluorouracil Phase II clinical study results showed that the objective efficiency rate (ORR) of 5-FU alone was about 0-40%, and the median overall survival (OS) was about 2-12 months; the ORR of Tegeo alone was about 35.0%, and the 1-year survival rate was about 40.0% (95% CI,26.5-53.1%) with a median OS of about 9.0-9.4 months; capecitabine alone had an ORR of about 6% and a median OS of about 8.1 months (95% CI,7.4-8.9 months). (2) The results of the phase II clinical study of gemcitabine showed that the ORR of gemcitabine alone was about 9.4-26.1%, median progression-free survival (PFS) was about 4.3-8.1 months, and median OS was about 9.2-13.1 months; while in a multicenter randomized controlled phase III clinical study reported by ValleJ et al, the results of gemcitabine monotherapy in first line treatment of advanced bile duct cancer, the disease control rate (DCR) was 71.8%, and the median OS and PFS were 8.2 months and 6.5 months, respectively. (1) Gemcitabine combined with platinum The results of the multicenter randomized controlled phase III clinical study (UK-ABC-02) conducted by ValleJ et al. showed that the DCR of gemcitabine combined with cisplatin in first-line treatment of advanced cholangiocarcinoma was 81.4%, and the median OS and PFS were 11.7 and 8.5 months, respectively, and the risk of death was reduced in the combination group compared with gemcitabine alone Based on the results of this study, gemcitabine in combination with cisplatin has now been adopted as the first-line standard of care for palliative chemotherapy in advanced cholangiocarcinoma. and PFS were 9.5 months and 4.2 months, respectively, with well-tolerated toxic reactions. (2) Gemcitabine in combination with fluorouracil Two phase II clinical studies showed that the ORR of gemcitabine in combination with tegeo in first-line treatment of advanced cholangiocarcinoma was about 20.0%, the 1-year survival rate was about 52.9% (95% CI,38.5-65.5%), and the median OS and PFS were about 8.9-12.5 months and 5.6 months. Two other phase II clinical studies investigated the efficacy of gemcitabine in combination with capecitabine in the first-line treatment of inoperable advanced cholangiocarcinoma/biliary cyst cancer, showing an ORR of approximately 31-35.6%, a DCR of approximately 73%, a 6-month survival rate of approximately 55% (95% CI,41-69%), a median OS of 7.0-14.0 months, and a median PFS of approximately 7 months, and further stratified analysis showed that the median OS and PFS of patients with bile duct cancer were 19.0 and 9.0 months, respectively. (3) Platinum combined with fluorouracil A phase II clinical study showed that tegeo combined with cisplatin in first-line treatment of patients with advanced cholangiocarcinoma had a 6-month PFS rate of 34.7% and a median OS of 9.9 months, while another phase II clinical study noted that capecitabine combined with cisplatin in first-line treatment of advanced cholangiocarcinoma/gallbladder cancer had an ORR of 40.6% (95% CI, 23.7-59.4%) and a median OS of 59.4%. 59.4%), with median OS and PFS of 12.4 months (95% CI,6.3-18.5 months) and 3.5 months (95% CI,1.3-5.8 months), respectively. (4) Other combination chemotherapy regimens In a phase II clinical study, 43 patients with advanced cholangiocarcinoma received epirubicin and cisplatin in combination with capecitabine in first line for a total of 187 cycles, with a median cycle number of 5 (range, 1-9), 17 patients achieved partial remission (40%,95%CI,21-49%), 10 had stable disease, and the median OS was 8 months after 18 months of follow-up ( After 18 months of follow-up, the median OS was 8 months (95% CI,6-10 months) with tolerable toxic effects; RaoS et al. conducted a phase III clinical study comparing the FELV regimen (5-FU, pedialyte glycosides, calcium folinate) with the ECF regimen (epirubicin, cisplatin, 5-FU), which enrolled only 54 patients over 6 years and forced the study to close midway. The results showed a median OS of 12.03 months (95% CI,9.3-14.7 months) and 9.02 months (95% CI,6.46-11.51 months) in the FELV and ECF groups, respectively, with ORRs of 15% (95% CI,3.2-37.9%) and 19.2% (95% CI,6.55-39.3%), respectively. The authors concluded that chemotherapy may provide good disease control and appears to prolong patient survival, but the study was not weighted enough to be of much reference value and cannot be routinely recommended. In conclusion, for first-line chemotherapy in advanced cholangiocarcinoma, the UK-ABC-02 study is the most complete and largest sample size clinical study to date, showing the survival benefit of gemcitabine combined with cisplatin regimen, which is now the first-line standard of care for palliative chemotherapy in advanced cholangiocarcinoma. In the selection of chemotherapy regimens, patients’ tumor status, physical status, willingness to treat and tolerance to chemotherapy need to be fully considered, so that the right chemotherapy can be administered to the right patient at the right time to ultimately help patients relieve tumor-induced symptoms (such as jaundice and pain), improve quality of life and prolong survival.