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

Purpose: To evaluate the safety, pharmacokinetics, and efficacy of a chimer ic anti-epidermal growth factor receptor monoclonal antibody, cetuximab, in combination with radation 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 s chedules. A standard dose escalation procedure was used; three patients ent ered onto the study at each dose level of cetuximab received conventional R T (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 Po 500 mg/m(2), followed by weekly infusions of 100 to 250 mg/m(2) for 7 to 8 weeks. Circulating levels of cetuximab during therapy were determined us ing a biomolecular interaction analysis core instrument. Human antichimeric antibody response was evaluated with a double-antigen radiometric assay. T he recommended phase II/III dose was defined as the optimal cetuximab dose level based on the pharmacologic parameters anal adverse events. Results: The most commonly reported adverse events were fever, asthenia, tr ansaminase elevation, nausea, and skin toxicities (grade 1 to 2 in most pat ients). Skin toxicity outside of the RT field was not strictly dose-depende nt: however, grade 2 or higher events were observed in patients treated wit h 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 Ri. The recommended d ose for phase II/III studies is a loading dose of 400 to 500 mg/m(2) and a maintenance weekly dose of 250 mg/m(2). (C) 2001 by American Society of Cli nical Oncology.