title: A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma: cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen).
abstract: OBJECTIVE
  PEFG regimen (P:cisplatin, E:epirubicin, F:5-fluorouracil, G:gemcitabine) significantly prolonged progression-free (PFS) and overall survival (OS) of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. The current trial was aimed at assessing whether the replacement of E with docetaxel (D) may improve 6 months PFS (PFS6).
  
  
  METHODS
  Chemo-naive patients with stage III or metastatic PA received P (30 mg/m(2) day 1 and 15), G (800 mg/m(2) day 1 and 15), and capecitabine (1,250 mg/m(2)/day days 1-28, without a break) and were randomized to receive either D at 25-30 mg/m(2) day 1 and 15 (arm A: PDXG regimen) or E at 30 mg/m(2) day 1 and 15 (arm B: PEXG regimen). Cycles were repeated every 28 days for a maximum of 6 months. The Fleming design was used to calculate the sample size on the probability of being PFS6. Assuming P0 = 40% and P1 = 60%, α = 0.05 and β = 0.10; the study was to enroll 52 patients per arm.
  
  
  RESULTS
  Between July 2005 and September 2008, 105 patients were enrolled, stratified by stage and randomized. Patients' characteristics were (A/B) the following: median age 61/59, PS >70 92/88%, metastatic disease 66/65%. PFS6 was 58%, and median OS was 11 months in both arms. A partial response was observed in 60/37% of patients. Main per cycle G3-4 toxicity was the following: neutropenia 4/13%, thrombocytopenia 2/4%, anemia 4/4%, and fatigue 6/3%.
  
  
  CONCLUSIONS
  The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens.
authors.affiliation: Department of Oncology, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy. reni.michele@hsr.it
authors.forename: Michele
authors.initials: M
authors.lastname: Reni
authors.forename: Stefano
authors.initials: S
authors.lastname: Cereda
authors.forename: Alessia
authors.initials: A
authors.lastname: Rognone
authors.forename: Carmen
authors.initials: C
authors.lastname: Belli
authors.forename: Michele
authors.initials: M
authors.lastname: Ghidini
authors.forename: Simonetta
authors.initials: S
authors.lastname: Longoni
authors.forename: Clara
authors.initials: C
authors.lastname: Fugazza
authors.forename: Sara
authors.initials: S
authors.lastname: Rezzonico
authors.forename: Paolo
authors.initials: P
authors.lastname: Passoni
authors.forename: Najla
authors.initials: N
authors.lastname: Slim
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Balzano
authors.forename: Roberto
authors.initials: R
authors.lastname: Nicoletti
authors.forename: Stefano
authors.initials: S
authors.lastname: Cappio
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Eugenio
authors.initials: E
authors.lastname: Villa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine