Cetuximab with irinotecan, folinic acid and 5-fluorouracil as first-line treatment in advanced gastroesophageal cancer: a prospective multi-center biomarker-oriented phase II study.
BACKGROUND
Cetuximab plus irinotecan/folinic acid/5-fluorouracil (5-FU) (IF) was evaluated as first-line treatment of patients with advanced gastric cancer and gastroesophageal junction tumors. Preplanned analyses of the influence of tumor biomarkers on treatment outcome were carried out.


METHODS
Patients received weekly cetuximab (400 mg/m(2) on day 1, subsequently 250 mg/m(2)) plus irinotecan (80 mg/m(2)) and a 24-hour continuous infusion of folinic acid (200 mg/m(2)) and 5-FU (1500 mg/m(2)) on days 1, 8, 15, 22, 29 and 36 of a 50-day cycle, until progressive disease (PD).


RESULTS
The most common grade 3/4 toxic effects in 49 patients were diarrhea (15%) and skin toxic effects (14%). In 48 assessable patients, the overall response rate was 46% and disease control rate was 79%. Median progression-free survival (PFS) and overall survival (OS) was 9.0 months [95% confidence interval (CI) 7.1-15.6] and 16.5 months (95% CI 11.7-30.1), respectively. Tumor response was more common than nonresponse in epidermal growth factor receptor-expressing tumors (P = 0.041). Tumor PTEN expression was associated with longer PFS (P = 0.035) and OS (P = 0.0127) than no PTEN expression.


CONCLUSIONS
Cetuximab plus IF was well tolerated and efficacy data were encouraging. This treatment combination and the role of selected biomarkers are under investigation in the ongoing phase III EXPAND trial.
First Department of Internal Medicine, University of Mainz, Mainz. Electronic address: moehler@mail.uni-mainz.de.
M
M
Moehler
First Department of Internal Medicine, University of Mainz, Mainz.
A
A
Mueller
Department of Medicine (Cancer Research), West German Cancer Centre, University Hospital of Essen, Essen.
T
T
Trarbach
Third Department of Internal Medicine, University Hospital, Technical University of Munich, Munich.
F
F
Lordick
First Department of Internal Medicine, University Hospital of Halle, Halle.
T
T
Seufferlein
Department of Gastroenterology and Hepatology, Center of Internal Medicine, Hannover Medical School, Hannover.
S
S
Kubicka
Department of Internal Medicine, City Hospital of Esslingen, Esslingen.
M
M
Geißler
First Department of Internal Medicine, University of Mainz, Mainz.
S
S
Schwarz
First Department of Internal Medicine, University of Mainz, Mainz.
P R
PR
Galle
First Department of Internal Medicine, University of Mainz, Mainz; Second Department of Medicine, Schweinfurt Hospital, Schweinfurt, Germany.
S
S
Kanzler
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068818:Cetuximab; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin