title: Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction.
abstract: BACKGROUND
  There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer. mFOLFOX6 is one of several active regimens used to treat adenocarcinoma of the Eso/GEJ. This study evaluates the efficacy and safety of mFOLFOX6 and erlotinib in patients with metastatic or advanced Eso/GEJ cancers.
  
  
  METHODS
  Patients with previously untreated advanced or metastatic Eso/GEJ adenocarcinoma are treated with oxaliplatin 85 mg m(-2), 5-FU 400 mg m(-2), LV 400 mg m(-2) on day 1, 5-FU 2400 mg m(-2) over 48 h and erlotinib 150 mg PO daily. Treatment was repeated every 14 days. The primary objective was response rate (RR), secondary objectives include toxicity, progression-free survival (PFS), overall survival (OS) and to correlate clinical outcome with expression patterns and molecular alterations in the epidermal growth factor receptor-dependent pathways.
  
  
  RESULTS
  A total of 33 patients were treated and evaluable: there were two complete responses, 15 partial responses for an objective RR of 51.5% (95% CI, 34.5-68.6%). Median PFS was 5.5 months (95% CI, 3.1-7.5 months) and median OS was 11.0 months (95% CI, 8.0-17.4 months). The most common grade 3-4 toxicities were: diarrhoea (24%), nausea/vomiting (11%), skin rash (8%) and peripheral neuropathy (8%). The frequency of alterations was KRAS mutations (8%), EGFR mutations (0%) and HER2 amplification (19%).
  
  
  CONCLUSIONS
  In patients with Eso/GEJ adenocarcinoma, mFOLFOX6 and erlotinib is active, has an acceptable toxicity profile and FOLFOX ± erlotinib could be considered for further development.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Geffen School of Medicine at UCLA, Los Angeles, CA, USA. zwainberg@mednet.ucla.edu
authors.forename: Z A
authors.initials: ZA
authors.lastname: Wainberg
authors.forename: L-S
authors.initials: LS
authors.lastname: Lin
authors.forename: B
authors.initials: B
authors.lastname: DiCarlo
authors.forename: K M
authors.initials: KM
authors.lastname: Dao
authors.forename: R
authors.initials: R
authors.lastname: Patel
authors.forename: D J
authors.initials: DJ
authors.lastname: Park
authors.forename: H-J
authors.initials: HJ
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Elashoff
authors.forename: N
authors.initials: N
authors.lastname: Ryba
authors.forename: J R
authors.initials: JR
authors.lastname: Hecht
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage*
chemical_list: D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D002955:Leucovorin; D005472:Fluorouracil