Researchers at Pusan National University, located in Busan, South Korea, found that FOLFIRINOX*, a combination chemotherapy used to treat patients with pancreatic cancer, may improve survival in patients with advanced biliary tract cancer (BTC)
A new collaborative study from Pusan National University and Yonsei University suggests that the FOLFIRINOX* regimen numerically improved survival outcomes compared with current standards such as FOLFOX**, FOLFIRI***, and nal-IRI/FL****, while maintaining manageable toxicity. These findings suggest that FOLFIRINOX could be a promising second-line treatment option for patients with advanced BTC following first-line chemotherapy failure, warranting further validation in prospective clinical studies.
Biliary tract cancers are invasive carcinomas that arise from the epithelial lining of the gallbladder and bile ducts, and include intrahepatic, perihilar, and extrahepatic cholangiocarcinoma and gallbladder cancer. BTCs are among the most aggressive gastrointestinal malignancies. To date, the best treatment outcomes are achieved through management by specialist multidisciplinary teams.[1]
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. It combined the results with a systematic review and meta-analysis of 21 studies from around the world. This paper was made available online on September 5, 2025, in the journal International Journal of Surgery. [2]
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,” explained Professor Kihun Kim, MD, Ph.D., is a Fellow in the Department of Occupational and Environmental Medicine at Pusan National University Yangsan Hospital..
Significant toxicity
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,” Kim concluded.
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.
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Note: * FOLFIRINOX is a combination chemotherapy regimen that includes oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2, administered intravenously every 14 days for 6 cycles.
** FOLFOX is a combination chemothery that includes: oxaliplatin 85 mg/m2 iv in 2 hours on day 1, calcium folinate 200 mg/m2 iv in 2 hours on day 1 and day 2, 5-Fu 400 mg/m2 iv on day 1 and day 2, and then continuous infusion of it at a dose of 600 mg/m2 for 44 hours. This regimen is repeated every 2 weeks.
*** FOLFIRI is a combination chemotherapy that includes Irinotecan 180 mg/m2 over a 90-minute infusion concurrently with leucovorin (folinic acid) 400 mg/m2 IV [or 2 x 250 mg/m2] as a 2-hour infusion during Irinotecan, immediately followed by a bolus dose of 5-fluorouracil (5-FU) 400-500 mg/m2 IV bolus and a 46-hour continuous infusion of 5-fluorouracil (5-FU) 2,400- 3,000 mg/m2 every 2 weeks.
**** Nal-IRI/FL is a chemotherapy regimen consisting of nanoliposomal irinotecan (nal-IRI) 70 mg/m² administered over 90 minutes, followed by leucovorin 400 mg/m² intravenously over 30 minutes, and fluorouracil 2400 mg/m² as a continuous intravenous infusion over 46 hours, repeated every 2 weeks.
Reference
[1] Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX. Biliary tract cancer. Lancet. 2021 Jan 30;397(10272):428-444. doi: 10.1016/S0140-6736(21)00153-7. PMID: 33516341.
[2] Leem G, Kim K, Kim J, Lee HS, Chung MJ, Park JY, Park SW, Kim YH, Bang S. Comparison of second-line chemotherapy regimens in advanced biliary tract cancer: a systematic review, meta-analysis, and population-based cohort study. Int J Surg. 2025 Sep 5. doi: 10.1097/JS9.0000000000003367. Epub ahead of print. PMID: 40910862.
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