Tarceva® Produces Responses in Recurrent Glioblastoma Multiforme
Researchers from the Cleveland Clinic Brain Tumor Institute have reported that Tarceva® (erlotinib) produced responses in more than 40% of patients with glioblastoma multiforme. These results were presented at the 29th European Society of Medical Oncology (ESMO) Congress held in Vienna, Austria, October 29 – November 3, 2004.
Approximately 17,500 people are diagnosed with primary brain cancer in the United States each year. Primary brain cancer is cancer that originates in the brain and has not spread from cancer already located elsewhere in the body. Glioblastoma is one of the most common, and fatal, types of primary brain cancer. When glioblastoma is present, glial cells become malignant and grow out of control. Glial cells are the most abundant cells present in the nervous system, providing many supportive functions that facilitate the majority of processes conducted by neurons (cells that transmit impulses between the brain, spinal column and nerves). Standard treatment options for glioblastoma consist of surgical removal of the cancer if possible, radiation therapy and/or chemotherapy. However, even with the most aggressive treatment available, most patients will survive less than one year after diagnosis. Because of the poor prognosis for patients with this disease, researchers are attempting to develop more effective treatment strategies to improve survival of glioblastoma patients.
One obstacle in the treatment of brain cancer is the inability of the majority of chemotherapy agents to penetrate the blood-brain barrier. The blood-brain barrier is a membrane that surrounds the brain and spinal cord and protects the brain and nervous system by allowing only very select molecules to pass through. Tarceva® is a small molecule biological therapy that may pass through the blood brain barrier.
Tarceva® is an epidermal growth factor receptor (EGFR) inhibitor. EGFRs are small proteins that are found on the surface of all cells. EGFR binds exclusively to small proteins circulating in the blood called growth factors. The binding action between EGFR and growth factors stimulates biological processes within the cell to promote growth of a cell in a strictly controlled manner. However, in many cancer cells, EGFR is either abundantly overexpressed or the EGFR biological processes that normally stimulate cell growth are constantly active, leading to the uncontrolled and excessive growth of the cancer cell.
There were 30 patients included in the Cleveland Clinic study. Patients were treated with 150 mg of Tarceva® per day until tumor progression or study withdrawl. Approximately 43% of patients (13/30) responded to treatment based on MRI. Six patients had a greater than 50% reduction in tumor size and 7 patients had stable disease for 3 months or more. Six months after treatment, 27% of patients were free of cancer progression. Notably, more than 10% of patients were progression free at one year after treatment. Tarceva® was well tolerated; there were no grade 3 or 4 side effects.
Reference: Vogelbaum MA, Peereboom D, Stevens GH, et al. Phase II study of single agent therapy with the EGFR tyrosine kinase inhibitor erlotinib in recurrent glioblastoma multiforme. Proceedings from the 29th ESMO Congress, Vienna, Austria, October 29 – November 3, 2004; (Abstract #783).
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