FOLFIRINOX shows promise as a second-line option for advanced biliary tract cancer

Biliary tract cancers, including intrahepatic, perihilar, and extrahepatic cholangiocarcinoma and gallbladder cancer, are among the most aggressive gastrointestinal malignancies. Treatment options remain limited once the disease progresses after first-line chemotherapy, and survival rarely exceeds one year.

To address this, the team of researchers led by Professor Yun Hak Kim from Pusan National University, analyzed 12 years of clinical data from 54 patients treated at Yonsei Severance Hospital and combined the results with a systematic review and meta-analysis of 21 studies from around the world. This paper was made available online on 05 September 2025 in the journal International Journal of Surgery.

The combined evidence suggests that FOLFIRINOX may provide better progression-free and overall survival than currently recommended regimens 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.

In this study, patients receiving FOLFIRINOX achieved a median progression-free survival of 4.2 months and an overall survival of 11.4 months. In the accompanying meta-analysis of 21 studies, FOLFIRINOX demonstrated numerically longer progression-free and overall survival compared with currently used second-line regimens such as FOLFOX, FOLFIRI, and nal-IRI/FL.

Still, the authors caution that toxicity remains significant. Nearly 40 percent of patients developed severe neutropenia, requiring dose adjustments or additional medical support. The team emphasizes that FOLFIRINOX should be reserved for fit patients under close supervision until further prospective trials confirm its broader safety.

Beyond short-term survival, the study highlights the potential to integrate biomarker-based selection and supportive strategies such as granulocyte colony-stimulating factor to mitigate toxicity. Future research may also explore pairing FOLFIRINOX with immunotherapies or molecular-targeted drugs. "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 paper provides an evidence-based foundation for clinicians considering treatment options after first-line chemotherapy failure and may guide updates to future BTC management guidelines.