title: Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: dose-finding study for the prospective multicenter, randomized, phase II/III REAL-3 trial.
abstract: OBJECTIVE
  Epirubicin, oxaliplatin, and capecitabine (EOC) is a standard treatment in advanced esophagogastric cancer. Panitumumab (P) is a fully human, immunoglobulin G2 monoclonal antibody targeting epidermal growth factor receptor. Randomized Trial of EOC +/- Panitumumab for Advanced and Locally Advanced Esophagogastric Cancer (REAL-3) will evaluate whether the addition of P to EOC improves survival in patients with advanced esophagogastric adenocarcinoma and undifferentiated carcinoma.
  
  
  METHODS
  The original design of REAL-3 added P 9 mg/kg to the standard dose of EOC (dose level [DL] + 1). Due to toxicity, a dose de-escalation was made to EOC + P DL-1 (epirubicin 50 mg/m(2), oxaliplatin130 mg/m(2), capecitabine 1,000 mg/m(2)/d + P 9 mg/kg every 3 weeks). After additional toxicity was observed, the study was amended to include two additional EOC + P dose levels. Using a 3 + 3 design, dose-limiting toxicities (DLTs) were assessed weekly during cycle 1. Patients were randomly assigned 1:1 to EOC +/- P.
  
  
  RESULTS
  Between July 2008 and October 2009, 29 patients were randomly selected for standard-dose EOC (n = 13) or EOC + P (n = 16). Five patients were treated at DL + 1, with grade 3 diarrhea in four of five patients by cycle 4. At DL-1, one patient had grade 3 diarrhea and grade 5 infection. Three patients were treated at DL-3, and then six were treated at DL-2, without DLTs.
  
  
  CONCLUSIONS
  The recommended dose for EOC + P is epirubicin 50 mg/m(2), oxaliplatin 100 mg/m(2), capecitabine 1,000 mg/m(2)/d, and P 9 mg/kg every 3 weeks. This dose has been selected for the ongoing phase II/III REAL-3 study.
authors.affiliation: Royal Marsden Hospital, London, UK.
authors.forename: Alicia F C
authors.initials: AF
authors.lastname: Okines
authors.forename: Sue E
authors.initials: SE
authors.lastname: Ashley
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Oates
authors.forename: Andrea
authors.initials: A
authors.lastname: Turner
authors.forename: Janine
authors.initials: J
authors.lastname: Webb
authors.forename: Claire
authors.initials: C
authors.lastname: Saffery
authors.forename: Yu Jo
authors.initials: YJ
authors.lastname: Chua
authors.forename: Ian
authors.initials: I
authors.lastname: Chau
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000077544:Panitumumab; D013274:Stomach Neoplasms / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D015251:Epirubicin; D000069287:Capecitabine; D000077544:Panitumumab; D005472:Fluorouracil