Biliary tract cancers, which include intrahepatic, perihilar, and extrahepatic cholangiocarcinoma as well as gallbladder cancer, are among the most challenging gastrointestinal cancers to treat. Once patients no longer respond to first-line chemotherapy, options become limited and survival rates typically remain low.
A research team led by Professor Yun Hak Kim from Pusan National University has analyzed 12 years of clinical data involving 54 patients at Yonsei Severance Hospital. Their findings were combined with a systematic review and meta-analysis of 21 international studies. The results were published online on September 5, 2025, in the International Journal of Surgery.
The study found that FOLFIRINOX may improve progression-free and overall survival compared to current second-line treatments such as FOLFOX, FOLFIRI, or nal-IRI/FL. "We conducted a meta-analysis integrating 12 years of real-world data on the use of FOLFIRINOX or mFOLFIRINOX as salvage treatment in patients with advanced BTC treated at the Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, along with all available published studies on second-line chemotherapy regimens for advanced BTC," said Prof. Kim.
Patients who received FOLFIRINOX had a median progression-free survival of 4.2 months and an overall survival of 11.4 months. In the meta-analysis covering multiple studies worldwide, FOLFIRINOX was associated with numerically longer survival than other second-line regimens.
However, significant side effects were observed: about 40 percent of patients developed severe neutropenia that required changes in dosing or additional medical intervention. The researchers advise that FOLFIRINOX should be considered only for fit patients under close monitoring until further trials can better establish its safety profile.
The study also suggests future directions such as using biomarkers to select appropriate patients and supportive measures like granulocyte colony-stimulating factor to reduce toxicity risks. Researchers are considering combinations with immunotherapies or targeted drugs in upcoming studies. "Our findings suggest that FOLFIRINOX may offer a potential benefit as a second-line treatment option for BTC following progression on first-line chemotherapy," concluded Prof. Kim.
This evidence may help guide clinicians when considering treatment after failure of initial chemotherapy and could influence updates to future guidelines for managing biliary tract cancer.
