A phase II clinical trial of an angiogenesis inhibitor to treat glioblastoma has shown promise in a majority of patients tested, say researchers at Massachusetts General Hospital and Harvard Medical School.
But they also say that the novel imaging and biomarker studies they performed as treatment was underway have revealed why the treatment, AZD2171, ultimately failed, and what might improve the response.
The imaging studies, which used specially adapted Magnetic Resonance Imaging (MRI) scans, exposed a “window” during which the blood system feeding the tumor reverted to a more normal state, before morphing again into the leaky, dilated vessels that make drug treatment difficult.
The blood biomarker studies showed that as tumors stopped relying on vascular endothelial growth factors (VEGF) to pump up blood flow to them -and VEGF is what AZD2171 targets-they started using two other growth factors, neither of which had previously been recognized as important for human tumor blood vessel growth.
The study is unique because it is the first to test AZD2171 in glioblastoma patients, and to find that it “offered promising benefits such as tumor shrinkage and reduction of brain swelling,” said Tracy Batchelor, M.D., chief of neuro-oncology at Massachusetts General Hospital.
Of 31 patients who participated, more than half experienced tumor shrinkage of 50 percent or more, and median time to tumor regrowth was 111 days. “This was not a randomized study, but compared to historical benchmarks, in which response to conventional therapies is approximately 10 percent and progression is usually 63 days, these results are encouraging,” Dr. Batchelor said.
The agent, which has been tested in other tumor types but is not yet approved, also reduced edema, or swelling, in the brain, he said. Because of that, some patients were able to stop using steroids, which can cause debilitating side effects.