{"entity":{"id":"paper-espac-1-chemoradiotherapy-chemotherapy-resected-pancreatic-nejm-2004","kind":"paper","name":"A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer","aka":[],"tldr":"The 2004 European trial that showed chemotherapy after pancreatic cancer surgery doubled five-year survival, while adding radiotherapy to the chemotherapy made survival worse, a result that split European and American practice for a decade.","summary":"ESPAC-1 used a two-by-two factorial design to randomise 289 patients with resected pancreatic ductal adenocarcinoma: 73 to chemoradiotherapy alone (20 Gy over two weeks plus fluorouracil), 75 to chemotherapy alone (fluorouracil), 72 to both and 69 to observation. With 237 deaths and a median follow-up of 47 months, the estimated five-year survival was 10 percent among patients assigned chemoradiotherapy and 20 percent among those who did not receive it (P = 0.05), and 21 percent among those who received chemotherapy against 8 percent among those who did not (P = 0.009); the chemotherapy benefit persisted after adjustment for prognostic factors. The authors concluded that adjuvant chemotherapy has a significant survival benefit whereas adjuvant chemoradiotherapy has a deleterious effect.","asOf":"2026-09-24","links":[{"label":"N Engl J Med 2004","url":"https://doi.org/10.1056/NEJMoa032295"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/15028824/"}],"tags":["pancreatic-evidence"],"related":["paper-espac-3-fluorouracil-vs-gemcitabine-adjuvant-neoptolemos-jama-2010","paper-conko-001-adjuvant-gemcitabine-observation-jama-2007","chemotherapy-roadmap"],"cancers":["pancreatic","resectable-pdac"],"sections":["chemotherapy","radiation"],"technologies":["cytotoxic-chemotherapy"],"targets":[],"drugs":["fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2004,"doi":"10.1056/NEJMoa032295","pmid":"15028824","authors":"Neoptolemos JP, Stocken DD, Friess H, et al.","paperType":"rct","findings":["289 resected patients in a two-by-two factorial design; 237 deaths at 47 months median follow-up.","Five-year survival 21 percent with chemotherapy against 8 percent without (P = 0.009).","Five-year survival 10 percent with chemoradiotherapy against 20 percent without (P = 0.05)."],"whatItMeans":"The origin of the European position that adjuvant treatment means chemotherapy alone; CONKO-001, ESPAC-3, ESPAC-4 and PRODIGE 24 all built on it, and the role of radiotherapy remains contested (LAP07, PREOPANC).","caveats":["The factorial design allowed clinician choice of randomisation options and background treatment, criticised at the time.","Split-course radiotherapy at 20 Gy is not modern chemoradiotherapy; the harm may not generalise."],"changedPractice":true,"participants":289},"route":"/key-papers/paper-espac-1-chemoradiotherapy-chemotherapy-resected-pancreatic-nejm-2004/","neighbours":{"paper":[{"id":"paper-conko-001-adjuvant-gemcitabine-observation-jama-2007","kind":"paper","name":"Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial","route":"/key-papers/paper-conko-001-adjuvant-gemcitabine-observation-jama-2007/"},{"id":"paper-espac-3-fluorouracil-vs-gemcitabine-adjuvant-neoptolemos-jama-2010","kind":"paper","name":"ESPAC-3: adjuvant fluorouracil plus folinic acid versus gemcitabine after pancreatic cancer resection","route":"/key-papers/paper-espac-3-fluorouracil-vs-gemcitabine-adjuvant-neoptolemos-jama-2010/"}],"roadmap":[{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"},{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}],"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"resectable-pdac","kind":"cancer","name":"Resectable pancreatic ductal adenocarcinoma","route":"/cancers/resectable-pdac/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"id":"radiation","kind":"section","name":"Radiation Therapy","route":"/fronts/radiation/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"drug":[{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"}],"term":[{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}