FOLFIRINOX in Digestive NEC: J of Neuroendocrinology | April 2026

Introduction

Digestive neuroendocrine carcinomas (NEC) are rare but highly aggressive malignancies with poor prognosis and limited therapeutic options. Standard first-line therapy consists of platinum plus etoposide, extrapolated from small-cell lung cancer, but outcomes remain suboptimal, particularly in colorectal NEC and tumours with intermediate Ki67 (20%–55%). In the absence of established second-line therapies, regimens effective in adenocarcinomas, such as FOLFIRINOX, are increasingly being explored in this setting.

Problem Statement

There is a significant unmet need for effective second-line or later-line treatment in digestive NEC. Current evidence is scarce, and treatment decisions are largely empirical, especially for patients progressing after platinum-based therapy or those with biologically distinct subgroups such as lower Ki67 tumours.

Summary

This Scandinavian multicenter retrospective study evaluated FOLFIRINOX in 50 patients with digestive NEC. The regimen demonstrated promising activity with an overall response rate of 44% and a disease control rate of 72%, alongside a median progression-free survival of 5.6 months. Notably, efficacy was maintained in challenging subgroups, including colorectal primaries, Ki67 <55%, and patients previously treated with platinum–etoposide. These findings suggest that FOLFIRINOX may represent a valuable therapeutic option beyond first-line treatment in NEC. Although limited by retrospective design, this study provides important real-world evidence supporting broader consideration of FOLFIRINOX in aggressive neuroendocrine malignancies.