Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients

Tania Crombet, Marta Osorio, Teresa Cruz, Carlos Roca, Ramón Del Castillo, Rosa Mon, Normande Iznaga-Escobar, René Figueredo, James Koropatnick, Enrique Renginfo, Eduardo Fernández, Daniel Alvárez, Olga Torres, Mayra Ramos, Idrissa Leonard, Rolando Pérez, Agustin Lage

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

273 Citas (Scopus)

Resumen

Purpose: To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. Patients and Methods: Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. Results: The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses, lmmunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. Conclusion: h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.

Idioma originalInglés
Páginas (desde-hasta)1646-1654
Número de páginas9
PublicaciónJournal of Clinical Oncology
Volumen22
N.º9
DOI
EstadoPublicada - 2004
Publicado de forma externa

Huella

Profundice en los temas de investigación de 'Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients'. En conjunto forman una huella única.

Citar esto