Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers.

Academic Article

Abstract

  • Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging. Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15). Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible. For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m2, cohort 2 received 25 mg/m2, and cohort 3 received 62.5 mg/m2. For panitumumab-IRDye800CW, cohorts received 0.06 mg/kg, 0.5 mg/kg, and 1 mg/kg, respectively. Electrocardiograms and blood samples were obtained, and patients were followed for 30 days post-study drug infusion. Results: Both fluorescently labeled antibodies had similar pharmacodynamic properties and minimal toxicities. Two infusion reactions occurred with cetuximab and none with panitumumab. There were no grade 2 or higher toxicities attributable to cetuximab-IRDye800CW or panitumumab-IRDye800CW; fifteen grade 1 adverse events occurred with cetuximab-IRDye800CW, and one grade 1 occurred with panitumumab-IRDye800CW. There were no significant differences in QTc prolongation between the two trials (p=0.8). Conclusions: Panitumumab-IRDye800CW and cetuximab-IRDye800CW have toxicity and pharmacodynamic profiles that match the parent compound, suggesting that other therapeutic antibodies may be repurposed as imaging agents with limited preclinical toxicology data.
  • Authors

    Keywords

  • Aged, Antibodies, Monoclonal, Antineoplastic Agents, Immunological, Benzenesulfonates, Cetuximab, ErbB Receptors, Female, Fluorescence, Fluorescent Antibody Technique, Head and Neck Neoplasms, Humans, Indoles, Male, Middle Aged, Panitumumab
  • Digital Object Identifier (doi)

    Author List

  • Gao RW; Teraphongphom N; de Boer E; van den Berg NS; Divi V; Kaplan MJ; Oberhelman NJ; Hong SS; Capes E; Colevas AD
  • Start Page

  • 2488
  • End Page

  • 2495
  • Volume

  • 8
  • Issue

  • 9