Chemotherapy plus radiation therapy prolonged OS in low-grade glioma

Issue: May 25, 2014

Patients with low-grade gliomas who underwent chemotherapy after radiation therapy survived 70% longer than patients who underwent radiation therapy alone, according to a long-term follow-up analysis of the NIH-supported RTOG 9802 trial.

Perspective from Pamela New, MD

“The results of this study are practice changing,” researcher Jan Buckner, MD, professor of oncology at Mayo Clinic in Rochester, Minn., said in a press release. “Ongoing analysis of patient tumor samples should allow us to further identify the patients who will, and who will not, benefit from chemotherapy, taking yet another step toward individualized therapy.”

Buckner and colleagues enrolled 251 patients with high-risk, low-grade glioma. Patients aged younger than 40 years were eligible if they had undergone less than complete surgical removal of their tumors.

All patients underwent surgery followed by radiation therapy.

Researchers then assigned half of the patients to PCV chemotherapy, consisting of procarbazine (Matulane, Sigma-Tau Pharmaceuticals), lomustine (CeeNu, Corden Pharma) and vincristine. Chemotherapy was administered in 21-day cycles every 8 weeks for a total of six cycles. The other patients received no additional treatment.

Median follow-up was 12 years.

Results released by NIH showed significantly longer median OS among patients assigned to PCV chemotherapy (13.3 years vs. 7.8 years).

“Patients who are deemed appropriate candidates for radiation therapy should be encouraged to receive chemotherapy as well, understanding both the potentials benefits and risks,” researcher Edward Shaw, MD, radiation oncologist at Wake Forest School of Medicine, said in the press release.

Full study results are expected to be published in a peer-reviewed publication and presented at a scientific meeting later this year, according to NIH.

For more information:

RTOG 9802: A phase II study of observation in favorable low-grade glioma and a phase III study of radiation with or without PVC chemotherapy in unfavorable low-grade glioma.

Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.

Perspective

Pamela New, MD

The RTOG 9802 trial presents provocative information. It is important to have evidence to show that patients who have been diagnosed with low-grade astrocytoma who have residual tumor may benefit from the addition of chemotherapy to radiation therapy. A final analysis of all enrolled subjects has not yet been assessed, as many patients are still alive and OS is an endpoint.

The chemotherapy chosen was PCV (procarbazine, CCNU and vincristine), as this was the treatment of choice in 1998 when the trial was initiated. In 1999, the drug temozolomide (Temodar, Schering-Plough) was approved for use in recurrent anaplastic astrocytoma. This is an oral drug and much better tolerated than the combination PCV, with fewer adverse effects. A prospective trial comparing these two regimens has never been done for any tumor type. It may be difficult to recommend an older, more toxic regimen, when we now have an improved agent available. This is a complication of trials that have a long duration until completion. Treatments and technology progress, yet the trial must go forward as originally designed.

Also, the investigators did not screen the tumor tissue for markers or genetics, such as 1p/19q loss of heterozygosity, MGMT status or IDH-1expression. This may also have provided corollary information as to response to therapy and prognosis.

In conclusion, the trial and the preliminary data are of great interest. Many questions remain to be answered.

Pamela New, MD

Neuro-oncology

Houston Methodist Hospital

Disclosures: New reports no relevant financial disclosures.