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Modified FOLFIRINOX regimen improves survival in resected pancreatic cancer
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A modified FOLFIRINOX regimen significantly improved survival compared with gemcitabine among patients with resected pancreatic cancer, according to a randomized phase 3 trial published in The New England Journal of Medicine.
However, FOLFIRINOX — which is composed of fluorouracil, leucovorin, irinotecan and oxaliplatin — was associated with a higher rate of adverse events.
FOLFIRINOX has been found to confer longer OS than gemcitabine when given as first-line treatment in patients with metastatic pancreatic cancer.
“The combination of bolus and continuous infusion fluorouracil, folinic acid, irinotecan and oxaliplatin was shown to better stabilize the quality of life, increase response rate in metastatic disease and increase survival compared with gemcitabine,” Thierry Conroy, MD, medical oncologist and director of the Institut de Cancerologie de Lorraine in France, said in an interview with HemOnc Today. “These promising efficacy results lead to the adjuvant trial project.”
In the randomized, multicenter, open-label PRODIGE 24-ACCORD trial, researchers enrolled 493 adults with pancreatic ductal adenocarcinoma who underwent surgery and had no signs of metastatic disease, malignant ascites or pleural effusion from 77 hospitals in France and Canada.
Researchers randomly assigned patients 3 to 12 weeks after surgery to the modified FOLFIRINOX regimen (85 mg/m2 oxaliplatin, 400 mg/m2 leucovorin, 180 mg/m2 irinotecan [later reduced to 150 mg/m2] and 2,400 mg/m2 fluorouracil) every 2 weeks or 1,000 mg/m2 gemcitabine on days 1, 8 and 15 every 4 weeks.
The modified FOLFIRINOX group (n = 247; median age, 63 years; range, 30-79) received a median 12 cycles (range, 1-12) for a median 24.6 weeks (range, 2-36.5). The gemcitabine group (n = 246; median age, 64 years; range, 30-81) received a median six cycles (range, 1-6) for a median 24 weeks (range, 3-36).
DFS served as the study’s primary endpoint, with OS and safety among the secondary endpoints.
Median follow-up was 33.6 months.
Results showed median DFS of 21.6 months (95% CI, 17.7-27.6) in the modified FOLFIRINOX group, compared with 12.8 months (95% CI, 11.7-15.2) in the gemcitabine group (stratified HR for cancer-associated event, second cancer or death = 0.58; 95% CI, 0.46-0.73).
At 3 years, the modified folfirinox group had a DFS rate of 39.7% (95% CI, 32.8-46.6) vs. 21.4% (95% CI, 15.8-27.5) in the gemcitabine group.
Modified FOLFIRINOX yielded median OS of 54.4 months (95% CI, 41.8-not reached), whereas median OS was 35 months (95% CI, 28.7-43.9) with gemcitabine (stratified HR for death = 0.64; 95% CI, 0.48-0.86).
At 3 years, researchers observed OS rates of 63.4% (95% CI, 55.7-70.1) in the modified FOLFIRINOX group and 48.6% (95% CI, 40.9-55.8) in the gemcitabine group.
Grade 3 or grade 4 adverse events occurred among 75.9% of patients in the modified FOLFIRINOX group vs. 52.9% of patients in the gemcitabine group. However, researchers noted that the safety profile of the regimen appeared to be manageable. There was one death in the gemcitabine group due to interstitial pneumonia.
The survival results seen with FOLFIRNOX support its routine use in certain patient populations, Conroy said.
“It should become one major option in routine practice; the survival results are the best results ever seen in an adjuvant trial,” he told HemOnc Today. “However, we performed this trial in selected patients with good performance status, recovery within 12 weeks from surgical operation and no cardiac contraindication to fluorouracil. I think that a cardiological opinion is preferable before chemotherapy, taking into account the use of the 5-FU as a continuous infusion.”
In a related editorial, Hedy L. Kindler, MD, medical director of gastrointestinal oncology and director of the mesothelioma program at University of Chicago Medical Center, called the results of the trial impressive.
“This trial represents the culmination of more than a decade of careful work that initially established FOLFIRINOX as a standard treatment for advanced pancreatic cancer,” Kindler wrote. “The remarkable results that have been achieved with adjuvant FOLFIRINOX therapy in the PRODIGE 24 trial have now changed the standard of care for many patients with resectable tumors. However, the majority of patients with pancreatic cancer present with far more advanced disease. For them, this is a recalcitrant cancer.” – by Jennifer Byrne
For more information:
Thierry Conroy, MD can be reached at Institut de Cancérologie de Lorraine 6 avenue de Bourgogne - CS 30519 54519 Vandœuvre-lès-Nancy Cedex; email: t.conroy@nancy.unicancer.fr
Disclosures: Conroy reports nonfinancial support from Roche outside the submitted work. Please see the study for all other authors’ relevant financial disclosures. Please see the editorial for a list of Kindler’s relevant financial disclosures.
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