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

Theranostics. 2018 Mar 28;8(9):2488-2495. doi: 10.7150/thno.24487. eCollection 2018.

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects*
  • Benzenesulfonates / administration & dosage
  • Benzenesulfonates / adverse effects*
  • Cetuximab / administration & dosage
  • Cetuximab / adverse effects*
  • ErbB Receptors / metabolism
  • Female
  • Fluorescence
  • Fluorescent Antibody Technique / methods
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / surgery*
  • Humans
  • Indoles / administration & dosage
  • Indoles / adverse effects*
  • Male
  • Middle Aged
  • Panitumumab / administration & dosage
  • Panitumumab / adverse effects*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • Benzenesulfonates
  • IRDye 800CW
  • Indoles
  • Panitumumab
  • ErbB Receptors
  • Cetuximab