Phase I study of anti–epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer

Authors

Francisco Robert, University of Alabama at Birmingham, USA
Mark Ezekiel, University of Alabama at Birmingham, USA
Sharon Spencer, University of Alabama at Birmingham, USA
Ruby Meredith, University of Alabama at Birmingham, USA
James Bonner, University of Alabama at Birmingham, USA
Mansoor Saleh, Aga Khan UniversityFollow
Delicia Carey, University of Alabama at Birmingham, USA
Albert LoBuglio, University of Alabama at Birmingham, USA
Richard Wheeler, University of Alabama at Birmingham , USA

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of a chimeric anti–epidermal growth factor receptor monoclonal antibody, cetuximab, in combination with radiation therapy (RT) in patients with advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: We treated 16 patients in five successive treatment schedules. A standard dose escalation procedure was used; three patients entered onto the study at each dose level of cetuximab received conventional RT (70 Gy, 2 Gy/d), and the final three patients received hyperfractionated RT (76.8 Gy, 1.2 Gy bid). Cetuximab was delivered as a loading dose of 100 to 500 mg/m2, followed by weekly infusions of 100 to 250 mg/m2 for 7 to 8 weeks. Circulating levels of cetuximab during therapy were determined using a biomolecular interaction analysis core instrument. Human antichimeric antibody response was evaluated with a double-antigen radiometric assay. The recommended phase II/III dose was defined as the optimal cetuximab dose level based on the pharmacologic parameters and adverse events. RESULTS: The most commonly reported adverse events were fever, asthenia, transaminase elevation, nausea, and skin toxicities (grade 1 to 2 in most patients). Skin toxicity outside of the RT field was not strictly dose-dependent; however, grade 2 or higher events were observed in patients treated with higher dose regimens. There was one grade 4 allergic reaction. Most acute adverse effects were associated with RT (xerostomia, mucositis, and local skin toxicity). No antibodies against cetuximab were detected. All patients achieved an objective response (13 complete and two partial remissions). CONCLUSION: Cetuximab can be safely administered with RT. The recommended dose for phase II/III studies is a loading dose of 400 to 500 mg/m2 and a maintenance weekly dose of 250 mg/m2.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Journal of clinical oncology

DOI

https://doi.org/10.1200/JCO.2001.19.13.3234DWTRG5YU7J

Recommended Citation

Robert, F., Ezekiel, M., Spencer, S., Meredith, R., Bonner, J., Saleh, M., Carey, D., LoBuglio, A., Wheeler, R. (2001). Phase I study of anti–epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer. Journal of clinical oncology, 19(12), 3234-3243.
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/95