Regimul FOLFIRINOX în tratamentul adjuvant şi metastatic al cancerului pancreatic în era oncologiei de precizie

Pancreatic cancer remains an aggressive disease with an unfavorable prognosis, although progress has been made in recent years. Thirty-five percent of patients with pancreatic cancer have locally advanced unresectable disease at diagnosis. Several studies have examined the systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with advanced local pancreatic cancer. FOLFIRINOX is now considered a standard first-line treatment because it has shown improved overall and progression-free survival in comparison with gemcitabine, proved by Conroy et al. in the ACOORD11-trial, associated with an increased toxicity profile. Currently, there are no validated biomarkers, efforts being made to identify molecular factors or biomarkers that predict the response to therapy in order to maximize the treatment efficacy and avoid unnecessary toxic effects for patients who do not respond to this combination of chemotherapy. New data indicate that molecular types of pancreatic ductal adenocarcinoma identified from immunohistochemistry (KRT81 and HNF1A) may predict the response to FOLFIRINOX or to gemcitabine-based regimen. Also, machine learning analysis of medical imaging has proven the ability to predict the response to one of the two chemotherapy regimens. Currently, FOLFIRINOX and Gem/nab-P are approved for the first line in locally advanced/metastatic pancreatic cancer, with a benefit regarding overall survival for FOLFIRINOX and a better toxicity profile for Gem/nab-P. PRODIGE 24-ACCORD demonstrates the superiority of a modified-attenuated FOLFIRINOX regimen (mFOLFIRINOX) in adjuvant settings versus gemcitabine chemotherapy. It is expected that mFOLFIRINOX may be a candidate for neoadjuvant treatment in locally advanced pancreatic cancer. Even though multiple molecular targets have been identified and the modulation of the tumor microenvironment is tried to improve the immunotherapy results, currently FOLFIRINOX regimen is the cornerstone of systemic therapy in pancreatic cancer.