Two weeks of single agent cetuximab (CET) induce a decrease in the tumor glucose-uptake measured by 18FDG-PET during neoadjuvant treatment of locally advanced squamous cell carcinoma (SCC) of the esophagus

Abstract

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Objectives: CET, a chimeric monoclonal antibody directed against epidermal growth factor receptor (EGFR) has proved therapeutic activity in SCC in-vitro and in-vivo by enhancing the activity of both chemo- and radiotherapy. Aim was to investigate the early influence of CET on tumor glucose metabolism.

Methods: Patients with locally advanced esophageal SCC received single agent CET for two weeks (400mg/m2 i. v. d -15 followed by 250mg/m2 d -8) before entering neoadjuvant chemoradiation (CRT): radiotherapy (45Gy cumulative dose; 1.8Gy/d), CET (250mg/m2) plus oxaliplatin and 5-FU cont. i.v. (doses according to dose escalation protocol). Surgery was scheduled 4-6 weeks after completion of CRT. Tumor FDG uptake was assessed by PET at baseline, two weeks after start of CET and two weeks after start of CRT. Tumor biopsies were taken before and two weeks after the start of CET.

Results: 5 of 6 patients are assessable for early metabolic changes. Decreases in the standard uptake value two weeks after the start of CET ranged from -7% to -44% for the for the early and from -17% to -51% for the later time point, respectively. So far, two patients underwent surgery (R0 resection both) and both were classified as histopathological responders. Immunohistochemical analyses (kinases involved in EGFR-dependent signal transduction, proteins representing proliferation and apoptosis) are under way.

Conclusions: This pilot study shows that the single agent CET has a clear and early repressive effect on tumor glucose uptake.