Conroy 2011: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer (PRODIGE 4/ACCORD 11)
A four-drug chemotherapy combination gave fit patients with metastatic pancreatic cancer clearly longer survival than the standard gemcitabine, the first real improvement in the disease in over a decade, at the cost of more side effects.
Overview
This French phase 2-3 trial randomised 342 patients with metastatic pancreatic adenocarcinoma and good performance status to FOLFIRINOX (oxaliplatin, irinotecan, leucovorin and fluorouracil) or gemcitabine. FOLFIRINOX improved overall survival, progression-free survival and response rate, and delayed the decline in quality of life despite more grade 3 and 4 toxicity, particularly neutropenia, febrile neutropenia, diarrhoea and sensory neuropathy. It made FOLFIRINOX a first-line standard for fit patients and the backbone later moved into the adjuvant setting.
- 342 patients with metastatic pancreatic cancer and ECOG performance status 0 or 1; FOLFIRINOX vs gemcitabine.
- Median overall survival 11.1 vs 6.8 months, hazard ratio 0.57.
- Median progression-free survival 6.4 vs 3.3 months, hazard ratio 0.47; response rate 31.6% vs 9.4%.
- Grade 3 or 4 neutropenia 45.7% vs 21.0%, febrile neutropenia 5.4% vs 1.2%, sensory neuropathy 9.0% vs 0%.
FOLFIRINOX and, soon after, gemcitabine plus nab-paclitaxel ended the era of single-agent gemcitabine for metastatic pancreatic cancer. The regimen's modified form later improved survival after surgery in PRODIGE 24, and its toxicity is why fitness, not just stage, decides which treatment a patient is offered.
- Restricted to fit patients under 76 with good performance status; most patients with pancreatic cancer are not eligible.
- Toxicity is substantial and needs experienced supportive care.
- Open-label design.
With FOLFIRINOX this trial defined the two chemotherapy standards for metastatic pancreatic cancer that still apply, and the gemcitabine and nab-paclitaxel backbone is the comparator in most current first-line pancreatic trials.
This trial introduced a patient-centred composite endpoint and a drug that remained the backbone of pancreatic cancer treatment for a generation. Its small survival gain also shows how low the bar was, which is the context for the FOLFIRINOX and MPACT trials that followed.
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Shares Irinotecan (and liposomal irinotecan), Fluorouracil (5-FU), Progression-free survival (PFS), Overall survival (OS).
- TermFOLFOX, FOLFIRI, FOLFIRINOX and CAPOX
Shares Oxaliplatin, Irinotecan (and liposomal irinotecan), Fluorouracil (5-FU), Pancreatic ductal adenocarcinoma.
- PersonDaniel D. Von Hoff
Shares MPACT (Von Hoff 2013): nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer, Pancreatic ductal adenocarcinoma.
- TreatmentGemcitabine + nab-paclitaxel
Shares MPACT (Von Hoff 2013): nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer, Pancreatic ductal adenocarcinoma.
- TargetRibonucleotide reductase (RRM1)
- TermFLOT regimen (perioperative chemotherapy for gastric cancer)
Shares Oxaliplatin, Fluorouracil (5-FU).
- IdeaSeamless phase 2/3 with pre-registered go rules as the default for new agents
Shares Progression-free survival (PFS), Overall survival (OS).
- TreatmentFOLFIRINOX / mFOLFIRINOX
Shares PRODIGE 24 / CCTG PA6, Pancreatic ductal adenocarcinoma.