The drug bevacizumab, also known by the trade name Avastin, shrinks tumors briefly in patients with an aggressive brain cancer known as glioblastoma multiforme, but then they often grow again and spread throughout the brain for reasons no one previously has understood. Now, Mayo Clinic researchers have found out why this happens. They have also discovered that pairing Avastin with another cancer drug, dasatinib, can stop that lethal spread. Dasatinib is approved for use in several blood cancers.
The findings, based on an animal study, are detailed in the Feb. 14 online issue of PLOS ONE. Based on those results, Mayo Clinic has already conducted a phase I clinical trial testing a combination of bevacizumab and dasatinib in glioblastoma patients whose other therapies failed. Mayo is now carrying out a randomized phase II study of 100 patients through Alliance for Clinical Trials in Oncology, a clinical trials network supported by the National Cancer Institute.
"We are very encouraged. This finding could potentially benefit many cancer patients," says co-author Panos Z. Anastasiadis, Ph.D., chair of the Department of Cancer Biology at Mayo Clinic in Florida. Working with him were researchers and oncologists from Mayo Clinic campuses in Florida and Minnesota.
The research began after Dr. Anastasiadis, a basic scientist who studies cell adhesion and migration, gave a seminar to a group of oncologists who treat brain tumors. The issue of bevacizumab-induced invasion was brought up and a collaboration to study it was quickly set up and funded by the Mayo Clinic Specialized Program of Research Excellence (SPORE) grant for brain cancer, one of only four in the country.
The issue of bevacizumab's induced aggressiveness is not limited to brain cancer, Dr. Anastasiadis says.
"While Avastin offers clear benefit in some patients, oncologists have noted that when cancers of many types recur after use of Avastin, they become aggressive and invasive," he says.