PRODIGE 4 ACCORD 11
Trial question
What is the effect of leucovorin, fluorouracil, irinotecan, and oxaliplatin regimen as first-line therapy in patients with metastatic pancreatic cancer?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
38.0% female
62.0% male
N = 342
342 patients (131 female, 211 male).
Inclusion criteria: patients with metastatic pancreatic cancer and an ECOG performance status score of 0 or 1.
Key exclusion criteria: age ≥ 76 years; endocrine or acinar pancreatic carcinoma; previous radiotherapy for measurable lesions; cerebral metastases; history of another major cancer; active infection; chronic diarrhea; clinically significant history of cardiac disease; pregnancy or lactation.
Interventions
N=171 FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks).
N=171 gemcitabine (at a dose of 1,000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks).
Primary outcome
Overall survival
11.1 months
6.8 months
11.1 months
8.3 months
5.5 months
2.8 months
0.0 months
FOLFIRINOX
Gemcitabine
Significant
increase ▲
Significant increase in overall survival (11.1 months vs. 6.8 months; HR 1.75, 95% CI 1.37 to 2.22).
Secondary outcomes
Significant increase in median progression-free survival (6.4 vs. 3.3; HR 2.13, 95% CI 1.69 to 2.7).
Significant increase in objective response (31.6% vs. 9.4%; RR 3.36, 95% CI 1.37 to 5.35).
Safety outcomes
Significant differences in adverse events, including febrile neutropenia (5.4% vs. 1.2%, p = 0.03) and definitive degradation of QoL (31% vs. 66%, p < 0.001; HR 0.47, 95% CI 0.30-0.70).
Conclusion
In patients with metastatic pancreatic cancer and an ECOG performance status score of 0 or 1, FOLFIRINOX was superior to gemcitabine with respect to overall survival.
Reference
Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25.
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