Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study)

Ann Oncol. 2007 Mar;18(3):510-7. doi: 10.1093/annonc/mdl459. Epub 2006 Dec 12.

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.

Patients and 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Cetuximab
  • Drug Administration Schedule
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction / pathology*
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Italy / epidemiology
  • Kaplan-Meier Estimate
  • Karnofsky Performance Status
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cetuximab
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • IFL protocol