title: Adjuvant PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) or gemcitabine followed by chemoradiation in pancreatic cancer: a randomized phase II trial.
abstract: BACKGROUND
  Information from randomized trials on the role of combination chemotherapy in the adjuvant treatment of pancreatic adenocarcinoma is limited. This randomized phase II trial aimed to identify the most promising regimen warranting phase III evaluation.
  
  
  METHODS
  Therapy-naive patients, age 18-75 years, Karnofsky Performance Status (KPS)>60, gross total resection of stage IB-III pancreatic adenocarcinoma, stratified for center and surgical margins, were randomly assigned to receive either gemcitabine 1 g/m2 weekly on days 1, 8, and 15 (arm A) or the PEFG regimen (cisplatin and epirubicin 40 mg/m2, day 1; gemcitabine 600 mg/m2, days 1, 8; 5-fluorouracil 200 mg/m2 daily, days 1-28) (arm B). Chemotherapy was administered every 4 weeks for 3 months and followed by irradiation concurrent to continuous infusion of 5-fluorouracil 250 mg/m2 daily. Primary endpoint was the probability of being disease-free at 1 year from surgery. Assuming P0=35% and P1=55%, α=.05 and β=.10, the study was to enroll 51 patients per arm.
  
  
  RESULTS
  A total of 102 patients were randomized; 100 were eligible (arm A: 51; arm B: 49). Baseline characteristic (A/B) were: Median age was 61/60 years; 75% had KPS>80 75/76%; 36% grade 3 tumor 29/43%, 79% stage IIB/III 75/84%, 31% R1 resection 35/29%. Survival figures (A/B) were: Median disease-free survival was 11.7 and 15.2 months; 1-year disease-free survival 49.0% (95% confidence interval [95% CI] 35-63%) and 69.4% (95% CI 56-83%); median survival 24.8 and 28.9 months. Combination chemotherapy produced more hematological toxicity without relevant differences in nonhematological toxicities.
  
  
  CONCLUSIONS
  The 4-drug regimen deserves further assessment in resectable pancreatic cancer.
authors.affiliation: Department of Oncology, S. Raffaele Scientific Institute, Milan, Italy. reni.michele@hsr.it
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Balzano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
authors.forename: Stefano
authors.initials: S
authors.lastname: Cereda
authors.forename: Paolo
authors.initials: P
authors.lastname: Passoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zerbi
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Tronconi
authors.forename: Carlo
authors.initials: C
authors.lastname: Milandri
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Saletti
authors.forename: Alessia
authors.initials: A
authors.lastname: Rognone
authors.forename: Clara
authors.initials: C
authors.lastname: Fugazza
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magli
authors.forename: Nadia
authors.initials: N
authors.lastname: Di Muzio
authors.forename: Valerio
authors.initials: V
authors.lastname: Di Carlo
authors.forename: Eugenio
authors.initials: E
authors.lastname: Villa
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine