# Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23)

Source: https://onco.cc/key-papers/paper-conroy-prodige-23-neoadjuvant-folfirinox-rectal-lancet-oncol-2021/  
OnCo record `paper-conroy-prodige-23-neoadjuvant-folfirinox-rectal-lancet-oncol-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Serious adverse events during adjuvant therapy were markedly fewer in the neoadjuvant group, which is the tolerability argument for moving chemotherapy forward.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: The Lancet Oncology
- Year: 2021
- DOI: 10.1016/S1470-2045(21)00079-6
- Authors: Conroy T, Bosset JF, Etienne PL, et al.
- 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.
- What it means: 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.

## Sources

- Lancet Oncol 2021: https://doi.org/10.1016/S1470-2045(21)00079-6
- PubMed: https://pubmed.ncbi.nlm.nih.gov/33862000/

## Connected records

- key papers: [Short-course radiotherapy followed by chemotherapy before total mesorectal excision versus preoperative chemoradiotherapy in locally advanced rectal cancer (RAPIDO)](https://onco.cc/key-papers/paper-bahadoer-rapido-short-course-radiotherapy-lancet-oncol-2021/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Rectal cancer](https://onco.cc/cancers/rectal-cancer/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/), [Radiation Therapy](https://onco.cc/fronts/radiation/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Radiotherapy](https://onco.cc/terms/radiotherapy/), [Total mesorectal excision (TME)](https://onco.cc/terms/total-mesorectal-excision/), [Total neoadjuvant therapy (TNT, rectal cancer)](https://onco.cc/terms/total-neoadjuvant-therapy/)
- technologies: [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/)
- drugs: [Capecitabine](https://onco.cc/drugs/capecitabine/), [FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/), [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/), [Oxaliplatin](https://onco.cc/drugs/oxaliplatin/)
- companies: [UNICANCER](https://onco.cc/companies/unicancer/)
- trials: [PRODIGE 23](https://onco.cc/trials/prodige-23/)
- people: [Thierry Conroy](https://onco.cc/people/thierry-conroy/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)
- roadmaps: [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](https://onco.cc/roadmaps/colorectal-roadmap/)

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