A Trojan Horse for Brain Cancer

Glioblastoma treatment with cediranib increases drug uptake

(RxWiki News) Blood flow is critical for cancer growth, especially in the brain, where cells are unable to survive without high levels of oxygen. Several drugs known as vascular endothelial growth factor (VEGF) inhibitors target this vulnerability.

One of the effects of chemotherapy and radiation is that the damaged cancer cells attempt to quickly grow, or metastasize to another place in the body.

Scientists theorized that adding one of these drugs, VEGF inhibitors, to brain cancer treatment would also stop the cancer by cutting off its ability to grow.

"Ask your oncologist about clinical trials in your area."

Led by board-certified neurologist Elizabeth Robins Gerstner, MD, researchers tested this starvation theory, and successfully discovered that using cediranib, a VEGF inhibitor, not only had an acceptable level of toxicity, but led to increased average survival in patients with glioblastoma. 

The team of seventeen scientists included doctors from the Massachusetts General Hospital as well as cancer researchers from the Dana-Farber Cancer Institute.

While data has been published online in an abstract, further results from the study will be presented at the American Society for Cancer Research's 2012 meeting in June.

The study design included the new drug cediranib in addition to the standard brain tumor chemotherapy using temozolomide, along with radiation treatment for advanced brain tumors.

The success of the drug in slowing the brain tumors was is measured by MRI scans. By looking at changes in blood flow over time, growth can be recorded. Rapid growth results in hot spots showing up on the scan where tumors are located.

VEGF inhibitors stop new blood vessel growth by acting on arteries directly, preventing normal growth activation which is automatically triggered by low levels of oxygen.

The study had two parts, a first stage with six patients to judge safety, and a second stage with 40 patients that followed.

Results from the third stage of the clinical trial are still pending, but the average overall survival of 786 days is a notable improvement in comparison to similar studies on glioblastoma in the past.

From the entire group of 46 patients, five still have no further evidence of cancer growth.

Results from the phase III clinical trial will include a direct comparison against the current treatment standard.

Initially developed for lung cancer in 2007, clinical trials for cediranib for the treatment of lung cancer were discontinued in early 2008 due to a lack of success, and the drug later failed a phase III clinical trial in early 2010 designed to show treatment superiority in cases of metastatic colon cancer.

Research presented at conferences is considered preliminary until publication in a peer-reviewed journal.

Study authors listed funding by the pharmaceutical corporations Merck, Novartis, AstraZeneca, Medimmune, and Roche.

Review Date: 
May 30, 2012