The role of cetuximab in the management of head and neck cancers
University of Pittsburgh Cancer Institute, Department of Radiation Oncology, Pittsburgh, PA 15232, USA.Expert opinion on biological therapy (Impact Factor: 3.74). 04/2012; 12(4):517-28. DOI: 10.1517/14712598.2012.667397
INTRODUCTION: The standard of care for patients with locally-advanced head and neck cancer is chemoradiation or surgical resection followed by radiation treatment with or without chemotherapy and despite aggressive, multimodality therapies with their associated toxicities, attempts are being made to improve efficacy while reducing toxicity. Cetuximab is a chimeric mAb directed against the EGFR that showed clinical activity in squamous cell carcinoma of head and neck (SCCHN). AREAS COVERED: Cetuximab is beneficial in recurrent and metastatic setting, as well as in the definitive setting. In a landmark study by Bonner et al., cetuximab was found to be effective in prolonging survival in conjunction with radiation treatment in locally-advanced tumors versus radiation therapy alone. The Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer (EXTREME) trial also showed an improvement in conjunction with chemotherapy in recurrent and metastatic tumors. EXPERT OPINION: Cetuximab is an important therapeutic option in SSCHN, and will continue to be used in metastatic and definitive settings. While cetuximab is a valuable tool in the treatment of SCCHN, more studies are needed to maximize the efficacy of this mAb in clinical settings and to identify the subpopulation of patients that truly benefit from its use.
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ABSTRACT: Introduction. In the absence of a published head-to-head trial between concomitant cisplatin-radiotherapy vs cetuximab-radiotherapy, we compared results of cetuximab vs cisplatin in unresectable HNSCC in our daily clinical practice. Materials and methods. We retrospectively analyzed all consecutive patients with unresectable HNSCC treated at Clinical Oncology Unit of the University Hospital of Ferrara (Italy) from October 2008 to February 2010. Results. We evaluated 21 patients: at last follow-up, 6 patients (28.6%) were deceased, 15 patients (71.4%) were alive and, among these, 13 (61.9%) were alive without evidence of disease (NED). Median follow-up time was 9.74 months. Median OS was 10.95 months. General characteristics were similar in the two subgroups, except for median age (low in cisplatin-subgroup: 55 vs 72) and the type of response (with a high numbers of complete response in cisplatin-subgroup). By the univariate analysis there was no statistical significance difference in OS (p= 0.898) between the two subgroups. Conclusion. Based on state-of-the-art, it was not possible to identify either treatment regimen as superior in prolonging either locoregional control or OS: our results seem to indicate that the two treatments may be equally efficacious and deferring the choice of treatment on the toxicity profile. Head-to-head trials are needed.Central European Journal of Medicine 04/2014; 9(2). DOI:10.2478/s11536-013-0154-9 · 0.15 Impact Factor
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ABSTRACT: The presence of the EMT (epithelial-mesenchymal transition), EndMT (endothelial-mesenchymal transition) and VM (vasculogenic mimicry) demonstrates the multidirectional extent of phenotypic plasticity in cancers. Previous findings demonstrating the crosstalk between head and neck squamous cell carcinoma (HNSCC) and vascular endothelial growth factor (VEGF) imply that HNSCC cells share some functional commonalities with endothelial cells. Our current results reveal that cultured HNSCC cells not only possess endothelial-specific markers, but also display endotheliod functional features including low density lipoprotein uptake, formation of tube-like structures on Matrigel and growth state responsiveness to VEGF and endostatin. HNSCC cell subpopulations are also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the endotheliod characteristics observed in vitro recapitulate phenotypic features observed in human HNSCC tumors. Conversely, cultured normal human oral keratinocytes and intact or ulcerated human oral epithelia do not express comparable endotheliod characteristics, which imply that assumption of endotheliod features is restricted to transformed keratinocytes. In addition, this phenotypic state reciprocity facilitates HNSCC progression by increasing production of factors that are concurrently pro-proliferative and pro-angiogenic, conserving cell energy stores by LDL internalization and enhancing cell mobility. Finally, recognition of this endotheliod phenotypic transition provides a solid rationale to evaluate the antitumorigenic potential of therapeutic agents formerly regarded as exclusively angiostatic in scope.Experimental Cell Research 01/2013; 319(7). DOI:10.1016/j.yexcr.2013.01.013 · 3.25 Impact Factor
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ABSTRACT: Positron emission tomography (PET) is a noninvasive molecular imaging technology that is becoming increasingly important for the measurement of physiologic, biochemical, and pharmacological functions at cellular and molecular levels in patients with cancer. Formation, development, and aggressiveness of tumor involve a number of molecular pathways, including intrinsic tumor cell mutations and extrinsic interaction between tumor cells and the microenvironment. Currently, evaluation of these processes is mainly through biopsy, which is invasive and limited to the site of biopsy. Ongoing research on specific target molecules of the tumor and its microenvironment for PET imaging is showing great potential. To date, the use of PET for diagnosing local recurrence and metastatic sites of various cancers and evaluation of treatment response is mainly based on [(18)F]fluorodeoxyglucose ([(18)F]FDG), which measures glucose metabolism. However, [(18)F]FDG is not a target-specific PET tracer and does not give enough insight into tumor biology and/or its vulnerability to potential treatments. Hence, there is an increasing need for the development of selective biologic radiotracers that will yield specific biochemical information and allow for noninvasive molecular imaging. The possibility of cancer-associated targets for imaging will provide the opportunity to use PET for diagnosis and therapy response monitoring (theranostics) and thus personalized medicine. This article will focus on the review of non-[(18)F]FDG PET tracers for specific tumor biology processes and their preclinical and clinical applications.Pharmacological reviews 07/2013; 65(4):1214-56. DOI:10.1124/pr.113.007625 · 17.10 Impact Factor
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