title: Phase II Study of Modified FOLFOX6 With Bevacizumab in Metastatic Gastroesophageal Adenocarcinoma.
abstract: BACKGROUND
  The median survival for patients with metastatic gastroesophageal adenocarcinoma is <12 months. Bevacizumab has demonstrated promising activity in metastatic gastroesophageal adenocarcinoma when used in combination with cisplatin-based regimens for patients from the Americas. We conducted a prospective phase II trial to investigate the efficacy of bevacizumab in combination with the oxaliplatin-based regimen, modified FOLFOX6, in patients with metastatic gastroesophageal adenocarcinoma.
  
  
  METHODS
  Patients with untreated metastatic adenocarcinoma of the stomach, gastroesophageal junction, or distal esophagus received mFOLFOX6 (leucovorin 400 mg/m, fluorouracil 400 mg/m bolus and 2400 mg/m continuous infusion over 46 h, oxaliplatin 85 mg/m) and bevacizumab (10 mg/kg) every 2 weeks until disease progression or intolerance. Response by RECIST was evaluated by CT scan every 8 weeks. The primary objective was progression-free survival (PFS); secondary objectives were safety, response rate, and overall survival (OS).
  
  
  RESULTS
  A total of 39 patients with untreated metastastic gastroesophageal adenocarcinoma were enrolled between September 2008 and June 2012. Median number of cycles administered was 12 (range, 4 to 86). The confirmed response rate was 56.4% (3 complete response and 19 partial response). The median PFS was 7.8 months and median OS was 14.7 months. Three patients remain on treatment, and 11 patients are alive, of whom 6 have survived >24 months. Treatment-related grade 3/4 toxicities included neutropenia (33.3%), neuropathy (20.5%), thromboembolism (VTE) (7.7%), thrombocytopenia (7.7%), anemia (2.6%), hypertension (2.6%), and proteinuria (2.6%). We observed no GI perforations or grade 3/4 GI hemorrhagic events.
  
  
  CONCLUSIONS
  First-line mFOLFOX6 with bevacizumab for metastatic gastroesophageal adenocarcinoma was well tolerated and associated with longer PFS and OS compared with historical data from similar populations treated without bevacizumab. Our results suggest that the addition of bevacizumab to mFOLFOX6 may provide clinical benefit in American patients with metastatic gastroesophageal adenocarcinoma, a finding consistent with previous studies of first-line bevacizumab in combination with chemotherapy for this disease.
authors.affiliation: Departments of *Internal Medicine, Section of Medical Oncology, Yale Cancer Center ∥Radiology, Yale School of Medicine ‡Yale Center for Analytic Sciences, New Haven †VA Connecticut Healthcare System, West Haven §Oncology Associates of Bridgeport, Fairfield, CT.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Yao
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Kortmansky
authors.forename: Neal A
authors.initials: NA
authors.lastname: Fischbach
authors.forename: Stacey
authors.initials: S
authors.lastname: Stein
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Deng
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Indukala
authors.initials: I
authors.lastname: Doddamane
authors.forename: David
authors.initials: D
authors.lastname: Karimeddini
authors.forename: Howard S
authors.initials: HS
authors.lastname: Hochster
authors.forename: Jill
authors.initials: J
authors.lastname: Lacy
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D004943:Esophagogastric Junction; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000556:secondary*
chemical_list: D020533:Angiogenesis Inhibitors; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil