{"entity":{"id":"paper-conroy-prodige-23-neoadjuvant-folfirinox-rectal-lancet-oncol-2021","kind":"paper","name":"Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23)","aka":[],"tldr":"Six cycles of a three-drug chemotherapy before the usual chemoradiotherapy raised three-year disease-free survival from 69 to 76 percent, and left patients with less nerve damage than giving the chemotherapy afterwards.","summary":"Conroy, Bosset, Etienne and colleagues ran a phase 3 open-label randomised trial at 35 French hospitals in adults aged 18 to 75 with newly diagnosed biopsy-proven cT3 or cT4 M0 rectal adenocarcinoma and WHO performance status 0 to 1. The neoadjuvant chemotherapy group received six cycles of FOLFIRINOX, then chemoradiotherapy (50 Gy over five weeks with concurrent capecitabine), total mesorectal excision and three months of adjuvant chemotherapy; the standard-of-care group received chemoradiotherapy, total mesorectal excision and six months of adjuvant chemotherapy. The primary endpoint was three-year disease-free survival in the intention-to-treat population.\n\nSerious adverse events during adjuvant therapy were markedly fewer in the neoadjuvant group, which is the tolerability argument for moving chemotherapy forward.","asOf":"2026-09-24","links":[{"label":"Lancet Oncol 2021","url":"https://doi.org/10.1016/S1470-2045(21)00079-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33862000/"}],"tags":["colorectal-evidence"],"related":["paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021"],"cancers":["colorectal","rectal-cancer"],"sections":["chemotherapy","radiation"],"technologies":["radiotherapy","imrt-igrt"],"targets":[],"drugs":["folfirinox","folfox","capecitabine","oxaliplatin","irinotecan"],"companies":["unicancer"],"institutions":[],"pathways":[],"terms":["total-neoadjuvant-therapy","chemoradiation","total-mesorectal-excision"],"trials":["prodige-23"],"people":["thierry-conroy"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2021,"doi":"10.1016/S1470-2045(21)00079-6","pmid":"33862000","authors":"Conroy T, Bosset JF, Etienne PL, et al.","paperType":"rct","findings":["At a median 46.5 months, three-year disease-free survival 76 percent (95 percent CI 69 to 81) against 69 percent (62 to 74): stratified hazard ratio 0.69 (0.49 to 0.97, p=0.034).","During neoadjuvant FOLFIRINOX the commonest grade 3-4 events were neutropenia (38 of 225, 17 percent) and diarrhoea (25 of 226, 11 percent).","During adjuvant chemotherapy, grade 3-4 peripheral sensory neuropathy occurred in 19 of 162 (12 percent) against 32 of 155 (21 percent).","Serious adverse events during adjuvant therapy in 18 of 163 (11 percent) against 36 of 158 (23 percent), p=0.0049.","Treatment-related deaths: one of 226 against two of 227."],"whatItMeans":"The second total neoadjuvant therapy schedule to change practice, and the one that shows the advantage is partly deliverability: chemotherapy given before an operation is completed by far more patients than chemotherapy given after one.","caveats":["FOLFIRINOX before chemoradiotherapy is demanding, and the trial enrolled patients up to 75 with good performance status.","No direct randomised comparison with the RAPIDO schedule exists.","Disease-free survival at three years, not overall survival, is the primary endpoint."],"changedPractice":true,"participants":461},"route":"/key-papers/paper-conroy-prodige-23-neoadjuvant-folfirinox-rectal-lancet-oncol-2021/","neighbours":{"paper":[{"id":"paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021","kind":"paper","name":"Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO)","route":"/key-papers/paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"rectal-cancer","kind":"cancer","name":"Rectal cancer","route":"/cancers/rectal-cancer/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"id":"radiation","kind":"section","name":"Radiation Therapy","route":"/fronts/radiation/"}],"term":[{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"radiotherapy","kind":"term","name":"Radiotherapy","route":"/terms/radiotherapy/"},{"id":"total-mesorectal-excision","kind":"term","name":"Total mesorectal excision (TME)","route":"/terms/total-mesorectal-excision/"},{"id":"total-neoadjuvant-therapy","kind":"term","name":"Total neoadjuvant therapy (TNT, rectal cancer)","route":"/terms/total-neoadjuvant-therapy/"}],"technology":[{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"folfirinox","kind":"drug","name":"FOLFIRINOX / mFOLFIRINOX","route":"/drugs/folfirinox/"},{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"},{"id":"irinotecan","kind":"drug","name":"Irinotecan (and liposomal irinotecan)","route":"/drugs/irinotecan/"},{"id":"oxaliplatin","kind":"drug","name":"Oxaliplatin","route":"/drugs/oxaliplatin/"}],"company":[{"id":"unicancer","kind":"company","name":"UNICANCER","route":"/companies/unicancer/"}],"trial":[{"id":"prodige-23","kind":"trial","name":"PRODIGE 23","route":"/trials/prodige-23/"}],"person":[{"id":"thierry-conroy","kind":"person","name":"Thierry Conroy","route":"/people/thierry-conroy/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}],"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"}]}}