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December 15th, 2016

Combination therapy improves survival in adults with glioma

By Nicole Brudos Ferrara

Radiation plus three-drug combo boosts progression-free survival and overall survival.

Patients with a low-grade type of brain tumor called glioma who received radiation therapy plus a chemotherapy regimen, including procarbazine, lomustine and vincristine (PCV), experienced a longer progression-free survival and overall survival than did patients who received radiation therapy alone.

These are the results of a clinical trial called Radiation Therapy Oncology Group (RTOG) 9802 that were published in the April 7, 2016, issue of the New England Journal of Medicine.

Jan Buckner, M.D.

"This is the first phase III trial to demonstrate conclusively a treatment-related survival benefit for patients with grade 2 glioma," said Jan C. Buckner, M.D., the study's lead author. Dr. Buckner is an oncologist and chair of the Department of Oncology at the Mayo Clinic Cancer Center in Rochester, Minnesota.

"Our early results, reported at a median patient follow-up of 5.9 years, showed that radiation therapy plus PCV chemotherapy was associated with a statistically significant prolongation of median progression-free survival, but not with overall survival. However, additional follow-up demonstrated an improvement in overall survival as well for these patients," Dr. Buckner said.

Between October 1998 and June 2002, 251 patients with low-grade glioma were enrolled in the RTOG 9802 clinical trial. Patients enrolled were at high risk compared to other patients with low-grade glioma because they were 40 or older or had a less-than-complete surgical removal of their tumors.

Patients were randomized to one of two trial arms: either radiation therapy plus six cycles of PCV chemotherapy, or radiation therapy alone. Before treatment, researchers conducted a pathology review on tumor samples and prepared samples for correlative laboratory studies to assess mutational status and identify prognostic variables.

At a median follow-up time of 11.9 years, 67 percent of enrolled patients were identified as having tumor progression and 55 percent of patients had died. Patients in the radiation therapy plus PCV chemotherapy arm had longer median survival times, compared with those in the trial arm who received radiation therapy alone (13.3 versus 7.8 years, respectively; p = 0.003).

Median progression-free survival time for patients receiving radiation therapy plus PCV chemotherapy versus radiation therapy alone was 10.4 years and 4.0 years, respectively. Ten-year, progression-free survival and overall survival rates for patients in the radiation therapy plus PCV chemotherapy arm versus those in the radiation therapy alone arm were 51 percent versus 21 percent and 60 percent versus 40 percent, respectively.

For progression-free survival and overall survival distributions, a difference between treatment arms became apparent only after two to four years after randomization. The favorable prognostic variables researchers identified for progression-free and overall survival included the radiation plus PCV chemotherapy arm and oligodendroglioma histology.

As expected, treatment toxicity was greater in the PCV chemotherapy arm and consistent with patients receiving multiagent chemotherapy regimens. The most common toxicities were fatigue, anorexia, nausea and vomiting, which were mostly grade 1 to 2 in severity with the exception of grade 3 to 4 neutropenia.

"Our results indicate that initial radiation therapy followed by PCV is necessary to achieve longer survival in patients with grade 2 glioma and that salvage therapy at relapse after radiation therapy alone is less effective," Dr. Buckner said. "It has also been hypothesized that other genetic alterations may be responsible for a small subset of patients whose glial brain tumors are chemotherapy resistant. However, radiation therapy plus PCV appears to represent the most effective treatment identified to date for the majority of patients with grade 2 glioma."

While grade 2 gliomas constitute only 5 to 10 percent of all brain tumors, they're responsible for progressive neurologic symptoms and premature death in nearly all patients diagnosed with this type of brain tumor.

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This article was originally published in Forefont, Mayo Clinic Cancer Center's online magazine.

Tags: About, brain cancer, cancer reseach, Findings, glioma, Jan Buckner, lomustine, PCV, procarbazine, Progress Updates, radiation therapy, vincristine

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