Adding Chemotherapy to Radiation Improves Survival for Some Patients with Rare Brain Cancer

Long-term follow-up results from two clinical trials confirm that certain patients with anaplastic oligodendrogliomas, which account for less than 10 percent of brain and central nervous system cancers, live substantially longer if they are treated with a combination of chemotherapy and radiation therapy rather than radiation alone.

In the trials—both of which were launched in the mid-1990s—patients whose tumor cells had missing or deleted parts of chromosomes 1 and 19 and who received the combination treatment lived substantially longer than patients whose tumors had these deletions but who received radiation therapy alone. About half of patients diagnosed with anaplastic oligodendroglioma have these chromosomal co-deletions. The combination treatment did not improve survival for patients whose tumor cells lacked the deletions.

Because of the immediate implications for patients, NCI and the Radiation Therapy Oncology Group (RTOG) announced the results of one of the trials, RTOG 9402, in January before they had been published or presented at a medical conference. Findings from both studies were presented in June 2012 at the American Society of Clinical Oncology annual meeting and published online October 15, 2012, in the Journal of Clinical Oncology (see journal abstracts here and here).

“These studies establish a new standard of care for patients with [anaplastic oligodendroglioma] tumors that harbor the 1p19q loss. No longer is radiation considered an adequate treatment for this patient population,” wrote Mark Gilbert, M.D., of the University of Texas MD Anderson Cancer Center in an accompanying editorial.

In the NCI-funded RTOG trial, participants whose tumors harbored both chromosomal deletions and who received high-dose chemotherapy with procarbazine (Matulane®), lomustine (CeeNu®), and vincristine (Vincasar®), a regimen known as PCV, followed by radiation had a median survival of 14.7 years. Participants with the deletions who received radiation alone had a median survival of 7.3 years. 

Median survival for patients whose tumors did not have the chromosomal deletions was less than 3 years, regardless of whether they received the combination therapy or radiation alone.

In the other trial, EORTC 26951, patients received radiation therapy alone or radiation followed by a standard-dose PCV regimen. The median overall survival cannot yet be calculated for patients with the chromosomal co-deletions who received the combination therapy, but there is a strong trend toward improved overall survival.

There is still some uncertainty about the preferred treatment for these patients, cautioned the RTOG trial’s principal investigator, Gregory Cairncross, M.D., of the University of Calgary and his colleagues. For example, because it can improve survival in glioblastoma, has fewer side effects, and is easier to administer than the PCV regimen, many oncologists appear to prefer using temozolomide (Temodar®) to treat anaplastic oligodendroglioma.

In January, enrollment was suspended for a clinical trial called CODEL that was to include only patients with 1p19q deletions and randomly assign them to radiation alone or radiation plus chemotherapy with temozolomide. Because the evidence so strongly supports the combination of chemotherapy and radiation for patients with the chromosomal deletions, a radiation-alone arm would be unethical, trial leaders explained.

According to Bhupinder Mann, M.B.B.S., of NCI’s Division of Cancer Treatment and Diagnosis, the trial is being redesigned, with the hope of finalizing the changes by the end of the year.