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Recentin Prolongs Survival in Patients With Glioblastoma: Presented at AACR

By Cameron Johnston

LOS ANGELES, CA -- April 19, 2007 -- The abnormal vasculature that is a hallmark of glioblastomas may be significantly reduced by a multi-targeted tyrosine kinase inhibitor of vascular endothelial growth factors (VEGF), cediranib (Recentin, also known as AZD 2171, AstraZeneca).

The researchers, who presented their findings here at the American Association for Cancer Research (AACR) annual meeting yesterday, say cediranib is also the first tyrosine kinase inhibitor to actually prolong survival in patients with any form of cancer - not just glioblastomas.

It is this abnormal growth of blood vessels that makes glioblastoma so difficult to treat, according to study presenter Tracy Batchelor, MD, MPH, chief, department of neurology, radiation oncology and radiology, Massachusetts General Hospital, Boston, Massachusetts, United States Median survival for patients with the disease is less than six months, he added.

The study involved 31 patients who had failed all other forms of treatment, including radiation and chemotherapy, and were treated with 45 mg/day of cediranib. Endpoints for the study were the number of patients who were still alive at six months, radiographic response, overall survival toxicity, and the presence or absence of angiogenic cytokines.

An interesting feature of the study was that patients were to undergo serial magnetic resonance imaging (MRI) scans within the first day of treatment, and this revealed a "direct and rapid effect on tumour vessels," Dr. Batchelor said. The change in tumour vasculature was "almost immediate" and "striking", he added.

"These were abnormal blood vessels and yet the size of the vessels was reduced almost immediately and the 'leakiness' of the vessels was reduced as well. As a consequence of these vessels normalising, we also saw a reduction in brain swelling and oedema, which is an important problem in this population because many of them will end up on steroids, which have their own detrimental effect," Dr. Batchelor said. "Our patients were able to reduce their use of steroids."

Overall, tumour volumes were reduced by more than 50% in half of the patients treated. This compares with a historical response rate of 10%, which has been the benchmark for treating glioblastomas.

"There was an improvement in progression-free survival as well as overall survival," he said. "But since this was not a randomised trial, the overall survival data has to be interpreted cautiously."

Finally, circulating proteins were also measured and elevations in two of these proteins -- basic fibroblast growth factor (bFGF) and stromal cell derived factor 1-alpha (SDF-1a) -- predicted tumour growth and, therefore, could be used as reliable markers to indicate when treatment was waning and the tumours had started to grow.

Dr. Batchelor said in an interview that the effect of the drug started to wear off within 28 days of discontinuation, although in some patients, the benefit was seen for up to four months.

Although this was a small pilot study, a larger phase 3 trial will be launched this year that will use cediranib in combination with other chemotherapies, as monotherapy and in combination with radiation therapy, he added.

The study was funded by the National Cancer Institute.


[Poster title: AZD2171, a Pan-VEGF Receptor Tyrosine Kinase Inhibitor, Normalizes Tumor Vasculature and Alleviates Edema in Glioblastoma Patients. Abstract 2118]

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