Abstract
BACKGROUND: Cetuximab, a monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR), has demonstrated activity in various tumor types. Using dynamic contrast-enhanced computed tomography (DCE-CT), we investigated the early activity of cetuximab monotherapy in previously untreated patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: Treatment-naïve patients with SCCHN received cetuximab for 2 weeks before curative surgery. Treatment activity was evaluated by DCE-CT at baseline and before surgery. Tumor vascular and interstitial characteristics were evaluated using the Brix two-compartment kinetic model. Modifications of the perfusion parameters (blood flow Fp, extravascular space ve, vascular space vp, and transfer constant PS) were assessed between both time points. DCE data were compared to FDG-PET and histopathological examination obtained simultaneously. Plasmatic vascular markers were investigated at different time points. RESULTS: Fourteen patients had evaluable DCE-CT parameters at both time points. A significant increase in the extravascular extracellular space ve accessible to the tracer was observed but no significant differences were found for the other kinetic parameters (Fp, vp or PS). Significant correlations were found between DCE parameters and the other two modalities. Plasmatic VEGF, PDGF-BB and IL-8 decreased as early as 2 hours after cetuximab infusion. CONCLUSIONS: Early activity of cetuximab on tumor interstitial characteristics was detected by DCE-CT. Modifications of plasmatic vascular markers are not sufficient to confirm anti-angiogenic cetuximab activity in vivo. Further investigation is warranted to determine to what extent DCE-CT parameters are modified and to evaluate whether they are able to predict treatment outcome.