# ESPAC-3: adjuvant fluorouracil plus folinic acid versus gemcitabine after pancreatic cancer resection

Source: https://onco.cc/key-papers/paper-espac-3-fluorouracil-vs-gemcitabine-adjuvant-neoptolemos-jama-2010/  
OnCo record `paper-espac-3-fluorouracil-vs-gemcitabine-adjuvant-neoptolemos-jama-2010` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

After surgery for pancreatic cancer, six months of gemcitabine gave the same survival as fluorouracil with folinic acid, about 23 months, with half as many serious side effects.

## Summary

Phase 3 trial at 159 centres in Europe, Australasia, Japan and Canada: 1,088 patients with resected pancreatic ductal adenocarcinoma were randomised to six months of fluorouracil plus folinic acid (551) or gemcitabine (537). The primary endpoint was overall survival.

After a median follow-up of 34.2 months and 753 deaths, median survival was 23.0 months with fluorouracil and 23.6 months with gemcitabine (hazard ratio 0.94, p 0.39); progression-free survival and quality of life did not differ. Treatment-related serious adverse events occurred in 14 percent of fluorouracil patients and 7.5 percent of gemcitabine patients.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Journal: JAMA
- Year: 2010
- DOI: 10.1001/jama.2010.1275
- Authors: Neoptolemos JP, Stocken DD, Bassi C, et al.
- Findings: Median overall survival 23.0 months (95% CI 21.1 to 25.0) with fluorouracil plus folinic acid versus 23.6 months (21.4 to 26.4) with gemcitabine; hazard ratio 0.94 (0.81 to 1.08).; Treatment-related serious adverse events in 14 percent versus 7.5 percent of patients (p < 0.001).
- What it means: Either regimen was acceptable adjuvant therapy in 2010, with gemcitabine preferred for tolerability; combination regimens (ESPAC-4, PRODIGE 24) have since superseded both.
- Caveats: Open-label; the observation arm was dropped after ESPAC-1, so the trial does not itself test chemotherapy against no chemotherapy.

## Sources

- JAMA 2010: https://doi.org/10.1001/jama.2010.1275
- PubMed: https://pubmed.ncbi.nlm.nih.gov/20823433/

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/)
- drugs: [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/)
- trials: [ESPAC-3](https://onco.cc/trials/espac-3/)
- journals: [JAMA](https://onco.cc/journals/jama/)

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