Real-world outcomes of fluorouracil-based second-line therapy in patients with advanced biliary tract cancer refractory to gemcitabine and cisplatin-based treatment.

The prognosis for patients with advanced biliary tract cancer (BTC) who have not responded to gemcitabine and cisplatin (GP)-based therapy is dismal. Fluorouracil (5-FU)-based chemotherapy could be considered for those patients who are refractory to GP-based treatments. Our study aimed to evaluate the real-world efficacy and safety of 5-FU-based chemotherapy for BTC patients who had progressed after gemcitabine-based treatment. This study analyzed patients from Seoul St. Mary's Hospital and St. Vincent's Hospital with advanced BTC who had previously failed treatment with GP-based chemotherapy. From June 2020 and May 2024, these patients received 5-FU-based chemotherapy as a second-line treatment. The 5-FU-based systemic treatments encompassed 5-FU, leucovorin, and oxaliplatin (FOLFOX); 5-FU, leucovorin, and liposomal irinotecan (Nal-IRI/FL); and 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). Our investigation focused on evaluating the survival outcomes and safety profiles of each regimen within this cohort. In our analysis of 147 patients, the primary tumor sites were distributed with 56 (38.1%) having intrahepatic cholangiocarcinoma, 51 (34.7%) with extrahepatic cholangiocarcinoma, and 40 (27.2%) with gallbladder cancer. Regarding the 5-FU-based regimens, 57 patients (38.8%) were treated with FOLFOX, 56 (38.1%) with Nal-IRI/FL, and 34 (23.1%) with FOLFIRINOX. The median progression-free survival (PFS) and overall survival (OS) were 2.3 months (95% confidence interval (CI), 2.0-2.6) and 4.8 months (95% CI, 3.8-5.8), respectively. Poor performance status and higher histologic grade were associated with worse PFS and OS, while female gender and prior surgery were linked to improved OS. FOLFOX and Nal-IRI/FL demonstrated comparable efficacy, with a median OS of 5.4 months (95% CI, 3.5-7.3) for FOLFOX and 4.7 months (95% CI, 2.6-6.9) for Nal-IRI/FL, and no significant differences were observed across subgroups. Grade 3 or higher neutropenia and biliary events were less frequent with FOLFOX, which also showed a lower incidence of adverse events and higher relative dose intensity than Nal-IRI/FL or FOLFIRINOX. In patients with advanced BTC who failed GP treatment, the FOLFOX regimen demonstrated comparable efficacy, and a more favorable safety profile compared to other 5-FU-based treatments. Given its favorable toxicity profile in a real-world setting, FOLFOX should be considered a standard second-line treatment option.