A combination chemotherapy regimen typically used for pancreatic cancer has demonstrated potential superiority over existing treatments for advanced biliary tract cancer, offering a promising new option for patients whose initial therapy has failed.

A joint Korean research team, including professors from Yonsei Cancer Center and Pusan National University Hospital (PNUH), found that FOLFIRINOX showed competitive efficacy and improved survival rates compared to other commonly used second-line drugs for the aggressive cancer.

The findings, recently published in the International Journal of Surgery, offer crucial clinical evidence where treatment standards are currently lacking.

Biliary tract cancer -- which includes intrahepatic, extrahepatic, and perihilar cholangiocarcinoma -- is typically diagnosed at an advanced stage, making surgical resection impossible for the majority of patients. For those with unresectable, advanced disease, the period without progression is often less than seven months, making the need for effective second-line therapy urgent. Currently, the average duration of maintained response for second-line treatments is around four months, and the overall effectiveness is not clearly established, leaving a gap in care.

FOLFIRINOX -- a regimen consisting of folinic acid, fluorouracil, irinotecan, and oxaliplatin -- had been hypothesized to be effective against biliary tract cancer due to the similarities in tumor progression with pancreatic cancer, where FOLFIRINOX is effective. However, studies confirming this had been absent until now.

The research team compiled results from 54 biliary tract cancer patients treated with FOLFIRINOX as a second-line therapy at Yonsei Cancer Center between 2011 and 2022. They combined this with a global meta-analysis of existing studies. The analysis focused on objective response rate (the proportion of patients whose tumors shrank), disease control rate (the proportion whose disease did not worsen), and overall survival.

The results showed that FOLFIRINOX had a relatively higher objective response rate of 15 percent, compared to 3 percent for FOLFIRI, 10 percent for FOLFOX, and 14 percent for Nal-IRI/FL (nanoparticle liposomal irinotecan).

FOLFIRINOX also demonstrated a higher disease control rate of 70 percent and the longest overall survival period at 9.13 months, compared to 5.93 months (FOLFIRI), 6.26 months (FOLFOX), and 8.41 months (Nal-IRI/FL).

Although the meta-analysis did not provide statistical significance due to the nature of indirect comparison, researchers noted FOLFIRINOX's strength. Notably, 5.6 percent of patients who had failed primary treatment achieved a complete response in the second-line FOLFIRINOX therapy, meaning the cancer was no longer visible on MRI imaging.

"We expect that, through future large-scale prospective clinical trials, FOLFIRINOX will be able to establish itself as the new standard of care in the second-line treatment of biliary tract cancer," said Professor Bang Seung-min at Yonsei Cancer Center, who led the study. 

Yonsei Cancer Center Professor Leem Ga-lam continued, saying, “We confirmed that FOLFIRINOX can be a new alternative in the second-line treatment of biliary tract cancer, where a standard treatment has not yet been established,” and added, “The fact that complete remission and long-term survival were observed in some patients particularly demonstrates the possibility of developing personalized treatment strategies.”

Professor Kim Jee-hoon provided a necessary caution, explaining that because FOLFIRINOX tends to have a higher rate of adverse reactions, such as bone marrow suppression, compared to other medications, doctors must be extremely diligent in their management and carefully select the appropriate patients for the regimen.

Yonsei Cancer Center is conducting a randomized prospective clinical trial of FOLFIRINOX for second-line treatment in biliary tract cancer patients. The team expects that the results of this meta-analysis, if consistent with the ongoing trial, will provide definitive evidence for establishing new treatment guidelines.