title: Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study).
abstract: BACKGROUND
  The purpose of this phase II study was to evaluate the efficacy and safety of cetuximab combined with FOLFIRI as a first-line treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
  
  
  METHODS
  Untreated patients with confirmed advanced gastric or gastroesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg/m(2) intravenously (i.v.) followed by weekly doses of 250 mg/m(2), CPT 11 180 mg/m(2) i.v. on day 1, LFA 100 mg/m(2) i.v. followed by 5-FU 400 mg/m(2) i.v. bolus, and 600 mg/m(2) i.v. 22-h continuous infusion on days 1 and 2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in patients with a complete response, partial response, or stable disease. Antitumor activity was assessed by computed tomography (CT) and positron emission tomography (PET) at baseline and after 6 weeks, and further by CT alone or CT and PET every 6 weeks.
  
  
  RESULTS
  Thirty-eight patients were enrolled (median age 63.5 years, range 39-83; median Karnofsky performance status 90, range 70-100; stomach 89.5% and GEJ 10.5%; locally advanced disease 13.2% and metastatic disease 86.8%). All 38 patients were assessed for safety and survival, and 34 patients were assessed for overall response rates (ORR). The ORR was 44.1% [95% confidence interval (CI) 27.5% to 60.9%]. The median time-to-progression was 8 months (95% CI 7-9). At the median follow-up time of 11 months, 55.3% of patients were alive, with a median expected survival time of 16 months (95% CI 9-23). Grade 3-4 toxicity included neutropenia (42.1%), acne-like rash (21.1%), diarrhea (7.9%), asthenia (5.3%), stomatitis (5.3%), and hypertransaminasemia (5.3%). There was one (2.6%) treatment-related death.
  
  
  CONCLUSIONS
  The combination of cetuximab and FOLFIRI is active in gastric and GEJ adenocarcinoma. The higher toxicity appears to be limited to neutropenia.
authors.affiliation: Medical Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy. cpinto@aosp.bo.it
authors.forename: C
authors.initials: C
authors.lastname: Pinto
authors.forename: F
authors.initials: F
authors.lastname: Di Fabio
authors.forename: S
authors.initials: S
authors.lastname: Siena
authors.forename: S
authors.initials: S
authors.lastname: Cascinu
authors.forename: F L
authors.initials: FL
authors.lastname: Rojas Llimpe
authors.forename: C
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: V
authors.initials: V
authors.lastname: Mutri
authors.forename: L
authors.initials: L
authors.lastname: Giannetta
authors.forename: S
authors.initials: S
authors.lastname: Giaquinta
authors.forename: C
authors.initials: C
authors.lastname: Funaioli
authors.forename: R
authors.initials: R
authors.lastname: Berardi
authors.forename: C
authors.initials: C
authors.lastname: Longobardi
authors.forename: E
authors.initials: E
authors.lastname: Piana
authors.forename: A A
authors.initials: AA
authors.lastname: Martoni
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin