FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer.
Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase III trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARC levels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microRNAs as predictive biomarkers.
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy.
Chiara
C
Caparello
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy.
Laura L
LL
Meijer
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy.
Ingrid
I
Garajova
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy.
Alfredo
A
Falcone
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy.
Tessa Y
TY
Le Large
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy.
Niccola
N
Funel
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy.
Geert
G
Kazemier
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy.
Godefridus J
GJ
Peters
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy.
Enrico
E
Vasile
Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy.
Elisa
E
Giovannetti
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D057285:Precision Medicine; D057170:Translational Research, Biomedical; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D000077146:Irinotecan; D066246:ErbB Receptors; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
FOLFIRINOX; MicroRNA; New treatments; Pancreatic cancer; Personalized therapy