Temodal Active in Anaplastic Astrocytoma

July 1, 1997

ASCO--The investigational agent temozolomide (Temodal) has shown activity in patients with relapsed anaplastic astrocytoma or oligoastrocytoma, with a tolerable side effects profile, said Victor Levin, MD, speaking for the Temodal Brain Tumor Group, a multidisciplinary worldwide group that participated in the investigation.

ASCO--The investigational agent temozolomide (Temodal) has shown activityin patients with relapsed anaplastic astrocytoma or oligoastrocytoma, witha tolerable side effects profile, said Victor Levin, MD, speaking for theTemodal Brain Tumor Group, a multidisciplinary worldwide group that participatedin the investigation.

Temozolomide, developed by Schering-Plough, is an oral cytotoxic agentof the imidazole class that penetrates the blood-brain barrier. It spontaneouslybiotransforms to MTIC, the active metabolite of DTIC (dacarbazine) "andtherefore should have few mechanisms available to allow cells to developresistance," said Dr. Levin, chairman of the Department of Neuro-Oncology,M.D. Anderson Cancer Center, in his ASCO presentation.

The phase II trial enrolled 163 patients from the United States, England,and France, and Dr. Levin reported on 100 patients who have been in thestudy for at least six months. The median time from radiotherapy to relapsefor these patients was 12.2 months. Patients who had received prior chemotherapy(58%) must have received a nitrosourea.

The temozolomide dosing schedule was 150 mg/m² for those who hadreceived prior chemotherapy and 200 mg/m² for those with no priorchemotherapy, given for five consecutive days, every 28 days. Evaluationwas every two months with gadolinium-enhanced MRI.

Myelosuppression was tolerable, Dr. Levin said, and nonhematologic adverseeffects, primarily nausea and vomiting, headaches, fatigue, and convulsions,were generally mild and easily managed.

As in most studies of anaplastic gliomas, he said, a significant numberof patients were not evaluable because of incorrect histology. Of the 100patients in this analysis, 59 actually had a diagnosis of anaplastic astrocytomaand were evaluable. However, all 100 patients were evaluated in this intent-to-treatstudy.

Overall, 41% of patients had an objective response, and 25% had stabledisease. "In brain tumor patients, because of slow dead cell removal,stabilization can mean quite a lot to patients," he said.

At six months, event-free survival was 48% overall by intent-to-treatanalysis and 51% among those with diagnosed anaplastic astrocytoma. One-yearevent-free survival was also similar in both groups at about 22%.

Patients who achieved a response did about 50% better than nonresponders,with median event-free survival of about 32% at one year.

Quality of life was assessed monthly using the EORTC measure and a modifiedbrain cancer module. "As you would intuitively expect, patients whorespond not only live longer but have better quality of life," Dr.Levin said. Among the responders who had low baseline quality of life scores,59% showed an improvement of global health measures of quality of lifeover the course of the study.

"The study is encouraging because there are few treatments nowavailable for this very aggressive type of brain tumor," Dr. Levinsaid. "The patients in the study tolerated the drug well, with nonegative impact on their quality of life."