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.

Abstract

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.

PATIENTS AND 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.

CONCLUSION:

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.

• Authors: M Moehler, A Mueller, T Trarbach, F Lordick, T Seufferlein, S Kubicka, M Geißler, S Schwarz, P R Galle, S Kanzler, German Arbeitsgemeinschaft Internistische Onkologie (AIO)
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 22 Issue 6 Pg. 1358-1366 (Jun 2011) ISSN: 1569-8041 [Electronic] England
• PMID: 21119032 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Cetuximab
• Esophageal Neoplasms (drug therapy)
• Female
• Fluorouracil (administration & dosage, adverse effects, therapeutic use)
• Humans
• Irinotecan
• Leucovorin (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Stomach Neoplasms (drug therapy)
• Treatment Outcome