Prospective Phase II Study of Neoadjuvant mFOLFOXIRI for Potentially Resectable Cholangiocarcinoma (NEOFOL)
In brief
After mFOLFOXIRI, 16 of 25 patients underwent curative-intent bile duct surgery
In this small, single-arm phase II study, 44% of patients' tumors shrank, and 16 of 25 patients underwent surgery intended to cure; 12 of those 16 had cancer-free margins. Severe neutropenia affected 36%, though no treatment-related deaths occurred. Whether the regimen improves outcomes over other approaches remains unknown and needs larger comparative studies.
- Journal
- International journal of cancer (Q1)
- Published
- 29 September 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Attapol Titapun, Aumkhae Sookprasert, Kosin Wirasorn, Piyakarn Watcharenwong, Thanachai Sanlung, Vor Luvira, et al.
- PMID
- 42806796
- DOI
- 10.1002/ijc.70758
Why clinicians should know about it
- Picked for Surgical Oncology (paper of the day, 3 October 2026): Neoadjuvant mFOLFOXIRI enables curative‑intent resection in CCA
Abstract
Cholangiocarcinoma (CCA) has poor outcomes despite curative-intent surgery. Neoadjuvant chemotherapy may improve tumor response and resectability. This study evaluated the efficacy and safety of neoadjuvant modified FOLFOXIRI (mFOLFOXIRI) in patients with potentially resectable CCA. In this prospective, single-arm, phase II study, 25 patients with potentially resectable cholangiocarcinoma received six cycles of neoadjuvant mFOLFOXIRI every 2 weeks. Surgical resection was performed when feasible. The primary endpoint was objective response according to RECIST version 1.1. Secondary endpoints included resectability, R0 resection, recurrence-free survival (RFS), overall survival (OS), safety, and health-related quality of life assessed using EQ-5D-5L. The objective response rate was 44.0%, with partial response in 11 patients, stable disease in 10 patients, and progressive disease in four patients. After neoadjuvant therapy, 20 patients (80.0%) were considered resectable, and 16 (64.0%) underwent curative-intent resection, with an R0 resection rate of 75.0%. Major pathological response occurred in two patients (12.5%). Among resected patients, seven (43.8%) had recurrence, with a median RFS of 18.93 months. The median OS in the overall cohort was 26.70 months. In unadjusted Kaplan-Meier analyses, radiologic response and surgical resection were significantly associated with longer overall survival. Grade 3-4 neutropenia occurred in 36.0% of patients, and no treatment-related deaths occurred. Health-related quality of life remained generally stable during treatment. Neoadjuvant mFOLFOXIRI showed promising antitumor activity, enabled a high rate of curative-intent resection, and demonstrated manageable toxicity in patients with potentially resectable cholangiocarcinoma. These findings support further investigation of this regimen as a neoadjuvant treatment strategy.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.