title: Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.
abstract: OBJECTIVE
  Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma.
  
  
  METHODS
  Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival.
  
  
  RESULTS
  Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed.
  
  
  CONCLUSIONS
  Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA. shah1@mskcc.org
authors.forename: Manish A
authors.initials: MA
authors.lastname: Shah
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: David H
authors.initials: DH
authors.lastname: Ilson
authors.forename: Alissa
authors.initials: A
authors.lastname: Levnor
authors.forename: David
authors.initials: D
authors.lastname: D'Adamo
authors.forename: Eileen
authors.initials: E
authors.lastname: O'Reilly
authors.forename: Archie
authors.initials: A
authors.lastname: Tse
authors.forename: Robin
authors.initials: R
authors.lastname: Trocola
authors.forename: Lawrence
authors.initials: L
authors.lastname: Schwartz
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schwartz
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin