Researchers at the University of Calgary say a new treatment plan for an aggressive brain cancer called glioblastoma is showing promise.

A combination of two drugs increased the lifespan of animals in test trials by 30 per cent, according to researchers at the Hotchkiss Brain Institute.

“It seems when the tumour is growing in the brain there’s multiple processes going on. So just shutting off this specific one doesn’t seem to have as much of an effect as hitting the cancer from different sides,” said Artee Luchman, one of the researchers.

“We’re just very encouraged by this study, which started as a lab inquiry research question, being moved into a human study.”

One drug is Temozolomide — already taken by most glioblastoma patients — while the other is AZD8055. Together they inhibit a pathway in the cancer cells known as mTOR signaling, causing more cancer cells to die when combined with current standard therapy.

Results of the study was recently published in the scientific journal Clinical Cancer Research.

Researchers hope to start a clinical trial next spring on people with glioblastoma, an aggressive form of brain cancer and the most common and deadly form among adults.

In patients identified with the IDH1-mutation and who had less than 2 cc of residual tumor, survival was greater than 95% over nearly 17 years, compared with a survival of 20% among patients with a larger residual tumor (P=0.01), said Daniel Cahill, MD, PhD, assistant professor of neurosurgery at Harvard.

“This is personalized surgery for these patients,” Cahill told MedPage Today at the annual meeting of the American Society of Clinical Oncology.

He said that the test to determine if the astrocytoma is wild type or is the mutant form requires no special testing. “It takes about a week to determine if the tumor is mutant or wild type. It is just an immunohistochemistry test. It is part of a routine, final pathology report.”

Cahill and colleagues reviewed data collected prospectively on 407 patients diagnosed with malignant astrocytomas from the University of Texas MD Anderson Cancer Center dataset. Researchers identified 121 patients for whom mutant status was determined. They had longer survival than patents with wild-type status.

When stratified by extent of residual tumor, the survival advantage was dramatic, Cahill demonstrated.

He said the study indicates that “with the finding of IDH1 status, you might do a second stage resection if necessary, because if we can get the residual tumor level to less than 2 cc we have patients out more than 20 years. You are basically cured,” he said.

The average survival for patients with the IDH1 mutation was 163.4 months, while the average survival for patients diagnosed with wild-type disease was 14.7 months. The patients with mutant disease were generally younger – 36.9 years of age compared with 55.9 years of age for those with wild-type disease.

Most of the patients with IDH1 mutant status were diagnosed with astrocytomas (87 of 121 patients), while the others were diagnosed with glioblastoma multiforme. He reported that 212 patients with wild-type status were diagnosed with glioblastoma and 43 were diagnosed with astrocytoma.

Overall, astrocytoma is a more favorable diagnosis, said Jennifer Clarke, MD, assistant professor of neurology and neurological surgery at the University of California San Francisco. “The IDH1 mutation tends to show up in patients whose tumors start as less aggressive and transform over time into more aggressive,” Clarke said.

“We are finding that IDH1-positive tumors and glioblastomas that are IDH1-negative are two different animals, and the question is whether we can translate that finding into differential treatment,” she told MedPage Today.

Clarke indicated that there may be subgroups of patients who respond differently to extent of surgery and to different medical regimens.

She said the mutation is much more common in low-grade tumors than in tumors first diagnosed as glioblastoma. “Glioblastoma is a grade 4 astrocytoma.”