Optimal Dosing Strategy for Fluorescence-Guided Surgery with Panitumumab-IRDye800CW in Head and Neck Cancer |
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Authors: | Nishio Naoki van den Berg Nynke S van Keulen Stan Martin Brock A Fakurnejad Shayan Zhou Quan Lu Guolan Chirita Stefania U Kaplan Michael J Divi Vasu Colevas Alexander D Rosenthal Eben L |
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Institution: | 1.Department of Otolaryngology-Head and Neck Surgery, Stanford University, 875 Blake Wilbur Drive, Palo Alto, CA, 94304, USA ;2.Department of Oral and Maxillofacial Surgery/Oral Pathology, VU University Medical Center/Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands ;3.Department of Pathology, Stanford University, Stanford, CA, USA ;4.Cancer Clinical Trials Office, Stanford Cancer Institute, Stanford University, Stanford, CA, USA ;5.Department of Medicine, Division of Medical Oncology, Stanford University, Stanford, CA, USA ; |
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Abstract: | Purpose To identify the optimal dosing strategy for fluorescence-guided surgery in patients with head and neck squamous cell carcinoma, we conducted a dose-ranging study evaluating the anti-epidermal growth factor receptor (EGFR) therapeutic antibody, panitumumab, that was fluorescently labeled with the near-infrared dye IRDye800CW. ProceduresPatients (n?=?24) received either 0.5 or 1.0 mg/kg panitumumab-IRDye800CW in the weight-based dosing group or 25 or 50 mg panitumumab-IRDye800CW in the fixed dosing group. Following surgery, whole primary specimens were imaged in a closed-field device and the mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were assessed. Clinical variables, including dose, time of infusion-to-surgery, age, unlabeled dose, gender, primary tumor site, and tumor size, were analyzed to evaluate the factors affecting the fluorescence intensity in order to identify the optimal dose for intraoperative fluorescence imaging. ResultsA total of 24 primary tumor specimens were imaged and analyzed in this study. Although no correlations between TBR and dose of panitumumab-IRDye800CW were found, there were moderate–strong correlations between the primary tumor MFI and panitumumab-IRDye800CW dose for fixed dose (mg) (R2?=?0.42) and for dose/weight (mg/kg) (R2?=?0.54). Results indicated that the optimal MFI was at approximately 50 mg for fixed dose and 0.75 mg/kg for dose/weight. No significant differences were found for the primary tumor MFI and TBRs between the weight-based dosing and the fixed dosing groups. MFIs significantly increased when the infusion-to-surgery window was reduced to within 2 days (vs. 3 days or more, p?<?0.05). ConclusionsAntibody-based imaging for surgical resection is under investigation in multiple clinical trials. Our data suggests that a fixed dose of 50 mg is an appropriate diagnostic dose for successful surgical fluorescence imaging. |
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