282 Use of the humanized anti-EGFR antibody h-R3 and radiotherapy for the treatment of patients with high-grade astrocytic tumors

Crombet, Tania; Figueredo, J.; Catala, Mauricio; González, Silvia; Selva, Juan Pedro Serrano; Toledo, Carolina; Torres, Osvaldo García; Pérez, Ramón; Lage, Agustín

doi:10.1016/s1359-6349(04)80290-8

Cited by 2 publications

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“…At the dose levels associated with systemic clearance saturation, nimotuzumab exhibits a more prolonged half-life and a higher area under the curve (4). Clinical trials with this antibody, involving >4,000 patients worldwide, have shown evidence of efficacy in the treatment of patients bearing advanced epithelial-derived tumors with low toxicity and without provoking skin rash, even when it was used alone or in combination with radiotherapy (5)(6)(7)(8)(9). At present, nimotuzumab is approved for therapeutic use in cancer treatment in several countries.…”

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confidence: 99%

Pharmacodynamic Trial of Nimotuzumab in Unresectable Squamous Cell Carcinoma of the Head and Neck: A SENDO Foundation Study

Rojo

Gracias

Villena

et al. 2010

Clinical Cancer Research

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Purpose: To assess the pharmacodynamic effects of nimotuzumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody with intermediate affinity for the receptor, in skin and tumor tissues from head and neck cancer patients.Experimental design: Pharmacodynamic study in patients with advanced squamous cell carcinoma of the head and neck, unsuitable for chemoradiotherapy, enrolled in a single-center trial. Patients received 8 weekly infusions of nimotuzumab. The first nimotuzumab infusion was administered 1 week before starting radiation, whereas the remaining doses were administered concomitantly with irradiation. Paired biopsies were taken from skin and primary tumors, before (pretherapy) and 1 week (on single-agent therapy) after first infusion. Immunohistochemistry was conducted to assay the effects of nimotuzumab on total and phosphorylated EGFR, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), p-AKT, and proliferation (Ki-67).Results: Nimotuzumab was well tolerated and there was no evidence of skin rash. Objective response was achieved in 9 of 10 patients. The pharmacodynamic assays showed inhibition of p-EGFR in both skin and tumor (P = 0.042 in skin and P = 0.034 in tumor). No significant changes in p-ERK1/2, p-AKT, or Ki-67 were detected in skin. In addition, lymphocytic infiltrates, folliculitis, or perifolliculitis were not observed. In tumor samples, there was an upregulation of p-AKT (P = 0.043), a reduction in proliferation index (P = 0.012), and a nonsignificant trend toward a decrease of p-ERK1/2 (P = 0.091).Conclusions: The pharmacodynamic data confirmed the ability of nimotuzumab to decrease EGFR phosphorylation. Downstream effects were observed in tumor cells but not in skin, a finding that may help to explain the lack of skin rash in patients treated with nimotuzumab.

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confidence: 99%

Pharmacodynamic Trial of Nimotuzumab in Unresectable Squamous Cell Carcinoma of the Head and Neck: A SENDO Foundation Study

Rojo

Gracias

Villena

et al. 2010

Clinical Cancer Research

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“…One patient developed antibodies to h-R3. Also, use of h-R3 in combination with radiotherapy in a phase I/II trial for the treatment of patients with high-grade astrocytic tumors revealed apparent improved survival compared with historical figures for standard radiotherapy or chemoradiotherapy schemes [41]. In total, 20 (87.5%) of 24 patients achieved stable disease at their best response, including four patients (16.7%) with complete response and five (20.8%) with partial response.…”

Section: Humanized Monoclonal Antibodiesmentioning

confidence: 97%

Clinical experience with monoclonal antibodies to epidermal growth factor receptor

Calvo

Rowinsky

2005

Curr Oncol Rep

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Recent knowledge about the intermediate steps and final consequences of ligand-dependent epidermal growth factor receptor (EGFR) activation has clearly supported the notion that EGFR plays a fundamental role in regulating the proliferation and survival of malignant neoplasms. Among the rationally designed target-based therapeutics that are being assessed, those targeting EGFR appear to be some of the most clinically relevant. The strategy of using monoclonal antibodies (mAbs) to block ligand binding to the extracellular domain of the EGFR has led to the development of therapeutics that robustly arrest malignant cell proliferation and, in some cases, induce profound tumor regression. The chimeric mAb against EGFR, cetuximab, has already been approved by regulatory agencies worldwide to treat patients with advanced colorectal cancer. Other mAbs against EGFR, particularly panitumumab (ABX-EGF), h-R3, and EMD72000, are in advanced stages of clinical development.

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282 Use of the humanized anti-EGFR antibody h-R3 and radiotherapy for the treatment of patients with high-grade astrocytic tumors

Cited by 2 publications

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Pharmacodynamic Trial of Nimotuzumab in Unresectable Squamous Cell Carcinoma of the Head and Neck: A SENDO Foundation Study

Pharmacodynamic Trial of Nimotuzumab in Unresectable Squamous Cell Carcinoma of the Head and Neck: A SENDO Foundation Study

Clinical experience with monoclonal antibodies to epidermal growth factor receptor

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