title: Oxaliplatin, irinotecan and cetuximab in advanced gastric cancer. A multicenter phase II trial (Gastric-2) of the Arbeitsgemeinschaft Medikamentose Tumortherapie (AGMT).
abstract: BACKGROUND
  Patients suffering from advanced gastric cancer still have a poor prognosis and treatment options are limited. In our previous phase II trial (AGMT-Gastric-1), we showed that the combination of oxaliplatin and irinotecan was well tolerated and effective. The same chemotherapy regimen was now tested in combination with cetuximab in a multicenter phase II trial.
  
  
  METHODS
  Oxaliplatin at 85 mg/m(2) biweekly and irinotecan at 125 mg/m(2) biweekly were combined with cetuximab at 400 mg/m(2) loading dose and subsequent weekly infusions of 250 mg/m(2). Fifty-one patients with histologically proven unresectable and/or metastatic gastric adenocarcinoma were treated in the first line setting. The median age was 62 years. A single metastatic site was found in 24 patients, 27 patients had multiple metastatic sites.
  
  
  RESULTS
  Frequently reported adverse events (in more than 20% of patients) were predominantly grade 1 or 2 and included neutropenia (35%), thrombocytopenia (33%), anemia (73%), nausea (45%), diarrhea (57%), alopecia (22%), and fatigue (37%). Grade 3/4 toxicities included neutropenia in 9/1 patients., thrombocytopenia in 1/0 patients, anemia in 3/1 patients, nausea in 2/0 patients, and diarrhea in 7/2 patients. Sensory neuropathy occurred mostly as grade 1 and 2 in 37% of patients, grade 3 neurotoxicity was observed in 7 patients. Acne-like rash grades 1/2/3/4 were reported in 31%/20%/6%/2% of patients respectively. Thirteen patients discontinued the study due to neutropenia (n=5), nausea/vomiting (n=1), diarrhea (n=1), toxic colon (n=2), and allergic reaction to cetuximab at first (n=2), second (n=1) or third infusion (n=1). Thirty-five patients were assessable for response, with 1 patient (3%) showing a complete response, 21 patients (60%) a partial response, 7 patients (20%) a stable disease, and 6 patients (17%) a progressive disease respectively. The median time to progression was 24.8 weeks, median overall survival was 38.1 weeks. All patients tested had a wild type KRAS status.
  
  
  CONCLUSIONS
  The combination of oxaliplatin and irinotecan with cetuximab is safe and its action established in advanced gastric cancer.
authors.affiliation: St.Vinzenz Krankenhaus Betriebs GmbH, Sanatoriumstr. 43, A-6511 Zams, Austria. e.woell@krankenhaus-zams.at
authors.forename: Ewald
authors.initials: E
authors.lastname: Wöll
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eisterer
authors.forename: Oliver
authors.initials: O
authors.lastname: Bechter
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fridrik
authors.forename: Birgit
authors.initials: B
authors.lastname: Grünberger
authors.forename: August
authors.initials: A
authors.lastname: Zabernigg
authors.forename: Beate
authors.initials: B
authors.lastname: Mayrbäurl
authors.forename: Gudrun
authors.initials: G
authors.lastname: Russ
authors.forename: Margit
authors.initials: M
authors.lastname: Dlaska
authors.forename: Peter
authors.initials: P
authors.lastname: Obrist
authors.forename: Josef
authors.initials: J
authors.lastname: Thaler
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics; D000068818:Cetuximab; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D000068818:Cetuximab; D002166:Camptothecin