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
| Autor: | Agustin Lage, Enrique Renginfo, Carlos Roca, I. Leonard, Rene Figueredo, Teresa Cruz, Daniel Esteban Pineda Alvarez, Ramón del Castillo, Tania Crombet, Normando Iznaga-Escobar, Rolando Pérez, James Koropatnick, Rosa Mon, Eduardo Fernández, Marta Osorio, Olga Torres, Mayra Ramos |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Oncology Cancer Research Pathology medicine.medical_specialty Antibodies Neoplasm Angiogenesis medicine.drug_class Biopsy medicine.medical_treatment Monoclonal antibody Growth factor receptor Antigen Internal medicine Humans Medicine Nimotuzumab Epidermal growth factor receptor Infusions Intravenous Aged Neovascularization Pathologic biology business.industry Carcinoma Head and neck cancer Antibodies Monoclonal Middle Aged medicine.disease Combined Modality Therapy ErbB Receptors Radiation therapy Treatment Outcome Head and Neck Neoplasms biology.protein Female business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 22:1646-1654 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 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. Immunohistochemistry 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. |
| Databáze: | OpenAIRE |
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