About Index

PRODIGE 4 ACCORD 11

"FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer". The New England Journal of Medicine. 2011. 364:1817-1825. PubMed

Links to original sources: Wiki Journal Post Full Journal Article

Contents 1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcome 8.2 Secondary Outcomes 9 Criticisms 10 Funding 11 Further Reading

Clinical Question


In patients with metastatic pancreatic cancer and good performance status, how does FOLFIRINOX compare with gemcitabine in terms of efficacy and safety?

Bottom Line


FOLFIRINOX compared with gemcitabine significantly prolongs survival in patients with metastatic pancreatic cancer who have good performance status, though with increased toxicity.

Major Points


FOLFIRINOX, a regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin, was associated with a significant improvement in survival over gemcitabine, the standard treatment for advanced pancreatic cancer, in this study. FOLFIRINOX resulted in a higher response rate and improved progression-free survival but exhibited higher toxicity.

Guidelines


As of my knowledge cutoff date in 2023, current oncology guidelines may consider FOLFIRINOX a first-line treatment option for selected patients with metastatic pancreatic cancer and good performance status. However, newer data may have emerged since then.

Design


Multicenter, randomized, phase 2-3 trial

Population


342 patients with metastatic pancreatic adenocarcinoma that had not been previously treated with chemotherapy.

Inclusion Criteria - Age 18 years or older - Histologically and cytologically confirmed, measurable metastatic pancreatic adenocarcinoma - ECOG performance status score of 0 or 1 - Adequate bone marrow, liver function, and renal function

Exclusion Criteria - Age of 76 years or older - Non-adenocarcinoma pancreatic cancers - Prior radiation for measurable lesions - Cerebral metastases - History of another major cancer - Active infection - Chronic diarrhea - Clinically significant cardiac disease - Pregnancy or breast-feeding

Baseline Characteristics - Median age: 61 years - Male: 56% - Metastases: liver (84%), lung (23%) - Performance status 0: 60%

Interventions


- FOLFIRINOX: oxaliplatin, irinotecan, fluorouracil, leucovorin every 2 weeks - Gemcitabine: weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks

Outcomes


Primary Outcome - Overall survival: 11.1 months with FOLFIRINOX vs 6.8 months with gemcitabine (P<0.001)

Outcomes


- Progression-free survival: 6.4 months with FOLFIRINOX vs 3.3 months with gemcitabine (P<0.001) - Response rate: 31.6% with FOLFIRINOX vs 9.4% with gemcitabine (P<0.001) - Increased toxicity with FOLFIRINOX, including neutropenia and febrile neutropenia

Criticisms


- Increased toxicity associated with FOLFIRINOX may limit its use. - The selection of patients with good performance status may not be representative of the general population with metastatic pancreatic cancer.

Funding


Funded by the French Ministry of Health, Amgen, and the French National League against Cancer, with drug donations from Sanofi-Aventis and Pfizer.

Further Reading


Full protocol, including the statistical analysis plan, available at NEJM.org.