# ESPAC-4: adjuvant gemcitabine plus capecitabine versus gemcitabine alone after resection of pancreatic cancer

Source: https://onco.cc/key-papers/paper-espac-4-gemcitabine-capecitabine-adjuvant-pancreatic-lancet-2017/  
OnCo record `paper-espac-4-gemcitabine-capecitabine-adjuvant-pancreatic-lancet-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding the tablet capecitabine to gemcitabine after surgery for pancreatic cancer lengthened median survival by about two and a half months with little extra toxicity, giving patients who cannot manage FOLFIRINOX a better option than gemcitabine alone.

## Summary

Open-label randomised phase 3 trial by the European Study Group for Pancreatic Cancer in 730 patients from 92 hospitals who had undergone complete macroscopic resection of pancreatic ductal adenocarcinoma. Patients received six cycles of gemcitabine alone or gemcitabine plus oral capecitabine.

Median overall survival was 28.0 months with the combination against 25.5 months with gemcitabine alone (hazard ratio 0.82). Five-year survival was higher with the combination, and grade 3 or 4 adverse events were similar between the arms apart from more hand-foot syndrome and diarrhoea with capecitabine.

## Fields

- Kind: Key paper
- Last checked: 2026-09-21
- Journal: The Lancet
- Year: 2017
- DOI: 10.1016/S0140-6736(16)32409-6
- Authors: Neoptolemos JP, Palmer DH, Ghaneh P, et al.
- Findings: Median overall survival 28.0 versus 25.5 months, hazard ratio 0.82.; Toxicity was similar overall, with more hand-foot syndrome and diarrhoea in the combination arm.
- What it means: Gemcitabine plus capecitabine became the adjuvant regimen for patients unfit for modified FOLFIRINOX, and remains the comparator in European trials of adjuvant treatment.
- Caveats: The absolute gain was modest and PRODIGE 24 soon showed a much larger benefit from modified FOLFIRINOX in fitter patients.; Many patients had R1 resections, so the trial population differs from strictly R0 series.

## Sources

- Lancet 2017: https://doi.org/10.1016/S0140-6736(16)32409-6
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28129987/

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)

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