Z Gastroenterol 2010; 48 - P127
DOI: 10.1055/s-0030-1263571

Cetuximab with irinotecan/FA/5-FU as first-line treatment in advanced gastro esophageal cancer: A prospective multi-center and biomarker-oriented phase II study

M Moehler 1, A Müller 1, T Trarbach 2, T Seufferlein 3, S Kubicka 4, M Geissler 5, F Lordick 6, S Daum 7, S Kanzler 8 P Galle 1, Arbeitsgemeinschaft Internistische Onkologie
  • 1Universität Mainz, Mainz, Germany
  • 2Universitäsklinikum Essen, Essen, Germany
  • 3Uniklinikum Halle/Saale, Halle, Germany
  • 4Uniklinikum Hannover, Hannover, Germany
  • 5Innere Klinik, Esslingen, Germany
  • 6Innere Klinik, Braunschweig, Germany
  • 7Uniklinikum Berlin, Berlin, Germany
  • 8Innere Klinik, Schweinfurt, Germany

To evaluate the tolerability and efficacy of cetuximab combined with irinotecan/folinic acid/5-fluorouracil (IF) as first-line treatment in patients with advanced gastric cancer and cancer of the gastroesophageal junction.

Patients and methods: Patients received weekly cetuximab (400mg/m2 day-1, subsequently 250mg/m2) plus irinotecan (80mg/m2) and a 24-hour continuous infusion of sodium folinic acid (200mg/m2) and 5-fluorouracil (1500mg/m2) on days 1, 8, 15, 22, 29 and 36 of a 50-day cycle, until tumor progression. In parallel tumors were assessed for KRAS, BRAF, and PIK3CA mutations by PCR and for EGFR, VEGF-C, SMAD4 and PTEN expression by immunohistochemistry; data were correlated with stage, response and survival.

Results: Between August 2006 and September 2007, 49 patients were enrolled, 27% of whom had carcinoma of the gastroesophageal junction. The most common grade 3/4 toxicities were diarrhea (15%) and skin toxicities (14%). Among 48 evaluable patients, overall response rate was 46% and disease control rate was 79%. Median progression-free and overall survival times were 9 months [95% CI 7.1 to 15.6] and 16.5 months (95% CI, 11.7 to 30.1), respectively.

In a subgroup analysis of 39 patients, VEGF-C expression levels correlated with the incidence of metastases, EGFR expression was associated with increased tumor stage and low EGFR levels correlated with lack of response (P=.035). Even more, high PTEN correlated with better progression-free and overall survival times (Logrank P=0.035 and P=0.0127).

Conclusion: Cetuximab plus IF was well tolerated and efficacy data were encouraging. These possible predictive biologic markers for EGFR1 targeted chemotherapy will be under further investigation in the ongoing phase III trial for advanced or metastatic gastric cancer.