title: Gemcitabine versus FOLFIRINOX in patients with advanced pancreatic adenocarcinoma hENT1-positive: everything was not too bad back when everything seemed worse.
abstract: OBJECTIVE
  hENT1 is a transmembrane protein which acts as a nucleoside transporter and is the main mediator of Gemcitabine (GEM) uptake into human cells. In this retrospective study we compared GEM versus FOLFIRINOX in patients with metastatic pancreatic cancer in which hENT1 evaluation was available.
  
  
  METHODS
  149 patients affected by unresectable metastatic pancreatic cancer, treated in our institution from 2009 to 2013, have been screened for inclusion in this retrospective study. Seventy patients, treated with GEM or FOLFIRINOX in first-line therapy, fulfilled clinical inclusion criteria for survival analysis. Thirty-one patients were available and contained sufficient quality/quantity RNA for evaluation of hENT1 expression by RT-PCR. The primary endpoint was OS and the secondary endpoint was PFS.
  
  
  RESULTS
  The survival analysis, carried out on 70 patients regardless of hENT1 expression, showed a statistically longer OS and PFS in the group treated with FOLFIRINOX compared to GEM. Within the exploratory analysis, which included 31 patients, no differences were found in hENT1 positive patients treated with FOLFIRINOX compared to GEM in terms of OS (8.5 vs 7 months, HR: 0.89; 95 % CI 0.3-2.5; p = 0.8) and PFS (5.5 vs 5 months, HR: 0.8, 95 % CI 0.2-2.2; p = 0.61). GEM-treated hENT1 positive patients showed a statistically significant improvement both of OS (8 vs 2 months; p = 0.0012) and PFS (5 vs 1 months; p = 0.0004) in comparison to GEM-treated hENT1 negative patients.
  
  
  CONCLUSIONS
  In our exploratory analysis GEM seems as effective as FOLFIRINOX in terms of survival with a better safety profile in hENT1 positive metastatic pancreatic cancer.
authors.affiliation: Department of Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy. armando.orlandi@edu.rm.unicatt.it.
authors.forename: A
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Department of Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Calegari
authors.affiliation: Department of Laboratory and Diagnostic Medicine, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Martini
authors.affiliation: Department of Laboratory and Diagnostic Medicine, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cocomazzi
authors.affiliation: Department of Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bagalà
authors.affiliation: Department of Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Indellicati
authors.affiliation: Department of Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Zurlo
authors.affiliation: Department of Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Basso
authors.affiliation: Department of Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cassano
authors.affiliation: Department of Laboratory and Diagnostic Medicine, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy.
authors.forename: L M
authors.initials: LM
authors.lastname: Larocca
authors.affiliation: Department of Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00136, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Barone
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D033721:Equilibrative Nucleoside Transporter 1; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; D009944:Organoplatinum Compounds; C438649:SLC29A1 protein, human; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine
keywords: FOLFIRINOX; Gemcitabine; Metastatic pancreatic adenocarcinoma; hENT1