O6–BG May Help Re-Sensitize Cancer Cells to Temodar® in Brain Cancer
According to a recent article published in the Journal of Clinical Oncology, the agent O6-BG may help to re-sensitize cancer cells to the chemotherapy agent Temodar® (temozolomide) in patients with recurrent brain cancer.
Approximately 20,000 people are diagnosed with primary brain cancer in the US each year. Primary brain cancer is cancer that originates in the brain (as opposed to cancer that has spread to the brain from elsewhere in the body). There are several different types of brain cancer. The cell type within the brain where the cancer originates determines the cancer type.
Treatment for brain cancer typically consists of surgery to remove as much of the cancer as possible, followed by chemotherapy and/or radiation therapy.
Temodar is a chemotherapy agent that is able to pass through the blood-brain barrier. The blood-brain barrier is a membrane that envelopes the brain and spinal cord. It protects the brain and spinal cord by allowing the passage of only very specific molecules. The majority of chemotherapy agents are not able to pass through the blood-brain barrier; this makes it difficult to reach cancer that has spread to or originated in the brain.
Although initial therapy with Temodar may produce anticancer responses, cancer commonly develops a resistance to the agent. This results in subsequent cancer progression or recurrence following initial treatment with Temodar. Once patients experience a cancer recurrence following treatment with Temodar, they have few effective treatment options. In order to counteract this, researchers have been evaluating ways to re-sensitize cancer cells to Temodar following a recurrence or progression after initial treatment with Temodar.
The agent O6-BG is still in early-phase clinical trials. It has demonstrated the ability to reverse resistance of cancer cells to Temodar and re-sensitive them to its repeated administration following a recurrence. To further test the optimal doses of O6-BG, as well as its effectiveness in re-sensitizing cancer cells to Temodar, researchers recently conducted a clinical trial evaluating O6-BG in patients with brain cancer.
This trial was conducted in multiple medical institutions and included 36 patients with recurrent brain cancer. All patients but one had received prior treatment with Temodar and had experienced a cancer recurrence. Patients were treated with O6-BG plus Temodar and evaluated for side effects and response.
Overall, one patient achieved a complete disappearance of cancer and 13 patients experienced disease stabilization for at least eight weeks. Treatment was well tolerated, and the optimal dose of O6-BG was established. These results will provide information necessary for the next phase of clinical trials evaluating O6-BG plus Temodar in patients with recurrent primary brain cancer.
The researchers concluded that O6-BG may help to re-sensitize cancer cells to Temodar in patients with brain cancer that has recurred following prior treatment with Temodar. Patients with recurrent brain cancer may wish to speak with their physician regarding the risks and benefits of participating in a clinical trial further evaluating O6-BG or other promising therapeutic approaches. Sources of information regarding ongoing clinical trials include the National Cancer Institute (www.cancer.gov).
Reference: Quinn J, Desjardins A, Weingart J, et al. Phase I Trial of Temozolomide Plus O6-Benzylguanine for Patients With Recurrent or Progressive Malignant Glioma. Journal of Clinical Oncology. 2005; 23: 7178-7187.