Anticancer agent - panitumumab
Dysregulation of the epidermal growth factor is associated with a number of cancerous processes, including angiogenesis, invasion and autonomous cell growth.
Dysregulation of the epidermal growth factor is associated with a number of cancerous processes, including angiogenesis, invasion and autonomous cell growth.
The transmembrane glycoprotein has an extracellular ligand binding domain and an intracellular domain that has tyrosine kinase activity for signal transduction. The receptor is expressed on healthy cells as well as malignant tissues, but overexpression is characteristic of many different malignant cells, and when this occurs the clinical prognosis is typically poor.
Abgenix and Amgen have been investigating panitumumab, a fully human immunoglobulin G2 monoclonal antibody that inhibits EGFR as a potential anticancer agent.1 A number of Phase II clinical studies have been carried out in patients with a variety of EGFR expressing cancers, including a two part study in patients with metastatic renal cell cancer.2 In the first part, patients with metastatic renal cell cancer were treated with panitumumab at each of four doses between 1.0 and 2.5mg/kg in weekly infusions for eight weeks. Those who responded or achieved stable disease were then given further weekly infusions for another eight months, or until their disease progressed. All patients completed the initial eight week cycle; of the 88 patients, three achieved a partial response, two a minor response, and half had their disease stabilised.
Another Phase II study was carried out in 148 patients with refractory metastatic colorectal cancer. Subjects, who had previously failed therapy with fluorpyridine plus irinotecan or oxaliplatin, or both, were given 2.5mg/kg of panitumumab every week. After eight weeks 15 patients had a confirmed partial response and 56 stable disease. The median overall survival was 7.9 months, the median time to progression was two months, and the drug was well tolerated.
A group of 19 patients with advanced non-small cell lung cancer were given 1.0, 2.0 or 2.5 mg/kg of panitumumab every week in combination with standard paclitaxel and carboplatin in an open label dose escalating study.4 After six weeks, one achieved a complete response and a further four partial responses.