Safety and Efficacy of Modified FOLFIRINOX in Unresectable or Metastatic Gallbladder Cancer: A Phase II Pilot Study

For unresectable gallbladder cancer (GBC), gemcitabine and platinum is standard combination; however, outcome is poor. We conducted this study to find feasibility of modified flourouracil, oxaliplatin, and irinotecan in this group. MATERIALS AND METHODS: We conducted a prospective, phase II single-arm pilot study. Inclusion criteria were histologically proven GBC and Eastern Cooperative Oncology Group 0-1. Primary end points were overall response rates and overall survival. The following treatment was given: oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2), and irinotecan 150 mg/m(2), all once on day 1, fluorouracil 2,400 mg/m(2) continuous intra-venous infusion over 46 hours repeated every 2 weeks, and maximum 12 doses, with primary granulocyte colony-stimulating factor prophylaxis. RESULTS: Between February 2019 and July 2020, 29 patients with unresectable GBC were enrolled. The median age was 52 years, and 18 were females. The Eastern Cooperative Oncology Group was 0 in 4. Five had bilirubin > normal, and 15 each had high serum alkaline phosphatase and carbohydrate antigen 19-9. Twenty-five patients had stage IV disease, and remaining unresectable locally advanced disease. A median of 8.5 cycles was given, and 11 completed treatment. Nine stopped chemotherapy because of progression, and one because of toxicity, and treatment is ongoing in three. Twenty-two required dose reduction. A treatment delay of 1-2 weeks was seen in 25 patients. Best response was complete response 1, partial response 13 (overall response rate 48.2%), and stable disease 9. Four patients with metastatic disease underwent R0 resection. As on cutoff date, nine are surviving (three without disease). Eighteen died of PD, and in two, cause was unknown. There was no toxic death. The median overall survival and progression-free survival were 309 and 252 days, respectively. Twenty-three patients experienced grade III or IV toxicity, and common were diarrhea (13), vomiting (12), and anemia (7). CONCLUSION: First-line modified flourouracil, oxaliplatin, and irinotecan is feasible in unresectable GBC with encouraging responses. Toxicities are higher but manageable. Higher response rates make this an option to explore in borderline resectable cases.