Clinical trialPhase 2/3Pancreatic cancer

FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer

N Engl J Med · 2011342 patients

Conroy T, Desseigne F, Ychou M, et al. N Engl J Med. 2011. 364:1817-1825

Study type: Clinical trial
Study name: PRODIGE 4 / ACCORD 11
Phase: Phase 2/3
Design: Multicentre randomised trial (France), open-label, 1:1 randomisation
Sample size: 342 patients
Source: N Engl J Med · 2011
Trial registration: NCT00112658

In plain words

This study was a turning point in the treatment of advanced pancreatic cancer. People in good general health who had the four-drug FOLFIRINOX regimen lived on average about 11 months, compared with about 7 months with gemcitabine alone, and the tumour shrank in about one third of them. This regimen has more side effects, but interestingly patients' quality of life declined later, probably because the disease was better controlled.

Key results

11.1 vs 6.8 months

Median overall survival

HR for death 0.57 (95% CI 0.45–0.73); P<0.001

6.4 vs 3.3 months

Median progression-free survival

HR 0.47 (95% CI 0.37–0.59); P<0.001

31.6% vs 9.4%

Objective response rate

P<0.001

31% vs 66%

Definitive deterioration in quality of life at 6 months

HR 0.47 (95% CI 0.30–0.70); P<0.001

Drugs in this study:Fluorouracil (5-FU)Gemcitabine (Gemzar)Irinotecan (Camptosar)Oxaliplatin (Eloxatin)

Dose and schedule cards

FOLFIRINOX (ACCORD 11)

First-line metastatic disease; ECOG 0–1Cycle length: Every 14 daysOn the page “Pancreatic cancer” · Metastatic disease: first-line, maintenance and later lines

First-line metastatic disease; ECOG 0–1

Drug	Dose	Route	Schedule
Oxaliplatin	85 mg/m²	IV over 2 hours	Day 1
Irinotecan	180 mg/m²	IV over 90 minutes	Day 1
Leucovorin	400 mg/m²	IV over 2 hours	Day 1
Fluorouracil (bolus)	400 mg/m²	IV bolus	Day 1
Fluorouracil (infusion)	2400 mg/m²	IV, 46-hour continuous infusion	Starting Day 1

Cycle length: Every 14 days
Duration: In responding patients, 6 months of chemotherapy was recommended

Doses from ACCORD 11; infusion durations of oxaliplatin and leucovorin (120 minutes) and irinotecan (90 minutes) per the FDA labels.

On the page “Pancreatic cancer” · Metastatic disease: first-line, maintenance and later lines

FOLFIRINOX (metastatic disease)

Metastatic pancreatic cancer, first line, ECOG 0 to 1Cycle length: Every 14 daysOn the page “FOLFIRINOX and mFOLFIRINOX: dose and side effects”

Metastatic pancreatic cancer, first line, ECOG 0 to 1

Drug	Dose	Route	Schedule
Oxaliplatin	85 mg/m²	IV over 2 hours	Day 1
Leucovorin	400 mg/m²	IV over 2 hours	Day 1
Irinotecan	180 mg/m²	IV over 90 minutes	Day 1
Fluorouracil	400 mg/m²	IV bolus	Day 1
Fluorouracil	2400 mg/m²	Continuous 46-hour infusion	Starting on day 1

Cycle length: Every 14 days
Duration: 6 months were recommended in the original study, then based on response and tolerance

Doses as in the PRODIGE 4/ACCORD 11 study. Many centres omit the bolus or reduce irinotecan to lower toxicity.

On the page “FOLFIRINOX and mFOLFIRINOX: dose and side effects”

FOLFIRINOX and modified FOLFIRINOX

Metastatic pancreatic cancer (ECOG 0 to 1); adjuvant treatment after pancreatic resectionCycle length: Every 14 daysOn the page “Oxaliplatin (Eloxatin)” · Standard doses and combination regimens (FDA label and key trials)

Metastatic pancreatic cancer (ECOG 0 to 1); adjuvant treatment after pancreatic resection

Drug	Dose	Route	Schedule
Metastatic
Oxaliplatin / irinotecan / leucovorin	85 / 180 / 400 mg/m²	IV	Day 1
Fluorouracil	400 mg/m² bolus, then 2400 mg/m²	IV bolus, then continuous 46-hour infusion	Days 1 to 3
Adjuvant (modified)
Oxaliplatin / irinotecan / leucovorin	85 / 150 (initially 180) / 400 mg/m²	IV	Day 1
Fluorouracil	2400 mg/m², no bolus	Continuous IV infusion	Day 1

Cycle length: Every 14 days
Duration: Metastatic: 6 months recommended in responding patients; adjuvant: 24 weeks (12 cycles)

The regimens of the PRODIGE 4/ACCORD 11 and PRODIGE 24 trials; not in the FDA label for oxaliplatin. In PRODIGE 24 the irinotecan dose was reduced from 180 to 150 mg/m² after a pre-specified safety analysis.

On the page “Oxaliplatin (Eloxatin)” · Standard doses and combination regimens (FDA label and key trials)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1FOLFIRINOX

Every 2 weeks: oxaliplatin 85 mg/m²; irinotecan 180 mg/m²; leucovorin 400 mg/m²; fluorouracil (5-FU) 400 mg/m² bolus followed by 2400 mg/m² as a 46-hour continuous infusion. In responding patients, 6 months of chemotherapy was recommended.

2Gemcitabine (control group)

Gemcitabine 1000 mg/m² weekly for 7 of 8 weeks, then weekly for 3 of every 4 weeks. In responding patients, 6 months of chemotherapy was recommended.

Source of the regimen details: Abstract of the NEJM 2011 paper (full dose and schedule of both groups)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Metastatic pancreatic cancer with no prior treatment (first line).
ECOG performance status 0 or 1.
Further details of the inclusion criteria (including age and bilirubin) in the full text of the paper.

Endpoints

Primary endpoint: overall survival.

Secondary endpoints: progression-free survival, objective response rate, safety and quality of life.

Safety and side effects

Adverse events were more frequent in the FOLFIRINOX group; febrile neutropenia occurred in 5.4% of patients in this group. The percentage of each grade 3 or 4 adverse event is reported in the full text of the paper. Despite greater toxicity, definitive deterioration in quality of life was less frequent in the FOLFIRINOX group.

Clinical significance and place in guidelines

ACCORD 11 made FOLFIRINOX one of the standards of first-line treatment for metastatic pancreatic cancer in patients with good performance status. The ESMO guideline (Express Update 2025) recommends FOLFIRINOX with level [I, A] and an ESMO-MCBS score of 5, and NCCN (version 4.2026) considers it a preferred category 1 option for patients with ECOG 0 to 1. In practice, the modified regimen (mFOLFIRINOX, usually without the 5-FU bolus) is commonly used to reduce toxicity. This regimen has no specific regulatory approval for pancreatic cancer but is widely recommended in guidelines.

Limitations

Only patients with ECOG 0 or 1 were enrolled and the inclusion criteria were strict (details of age and liver function in the full text of the paper), so the results cannot be generalised to older or frail patients. The study was open-label and conducted only in France, and the toxicity of the regimen is substantial.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.