|Note the discussion below under "Viewpoint" as to the best candidates for FOLFIRINOX: |
FOLFIRINOX Versus Gemcitabine for Metastatic Pancreatic Cancer Conroy T, Desseigne F, Ychou M, et al
N Engl J Med. 2011;364:1817-1825
Study Summary Gemcitabine has long been the standard of care for treatment of advanced pancreatic cancer. Numerous randomized clinical trials conducted in the past 2 decades have attempted to build upon single-agent therapy. For the most part, gemcitabine-based doublets have not shown substantial improvements in survival, although the gemcitabine-erlotinib combination has received US Food and Drug Administration approval as the first-line indication. In this article, investigators from France report on the utility of an aggressive regimen combining gemcitabine given in standard doses with both oxaliplatin and irinotecan (the FOLFIRINOX regimen). The study was a randomized phase 2 trial that was subsequently expanded to phase 3 design, in which 342 patients were randomly assigned to gemcitabine or FOLFIRINOX.
All of the study endpoints favored FOLFIRINOX: overall survival (11.1 vs 6.8 months), progression-free survival (6.4 vs 3.3 months) and response rates (31.6% vs 9.4%). Incidences of grade 3 or 4 neutropenia, febrile neutropenia, thrombocytopenia, diarrhea, and sensory neuropathy as well as grade 2 alopecia were significantly higher in the FOLFIRINOX arm. At 6 months, 31% of the patients in the FOLFIRINOX group had definitive reductions in their scores on the Quality of Life scale vs 66% in the gemcitabine group, suggesting that despite increased adverse events, patients receiving FOLFIRINOX had a better quality of life.
Viewpoint This is the first study to show substantial improvements in survival in advanced pancreatic cancer. It is unfortunate, however, that this gain occurs with an aggressive multichemotherapy regimen rather than with the addition of targeted therapy as many had hoped for. Although the efficacy of the regimen is clear and substantial, concerns about toxicity and tolerability are ongoing. Anecdotally, many oncologists are empirically reducing starting doses for this regimen, especially of irinotecan. The use of growth factor support should also reduce the risk for febrile neutropenia. Careful patient selection is exceedingly important: Patients who are younger, wishing to seek more aggressive treatment, and who have an excellent performance status are the best candidates for FOLFIRINOX.