Prospective Phase II Study of Neoadjuvant mFOLFOXIRI for Potentially Resectable Cholangiocarcinoma (NEOFOL).

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.