ASCO--The investigational agent temozolomide(Drug information on 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.
Temozolomide, developed by Schering-Plough, is an oral cytotoxic agent of the imidazole class that penetrates the blood-brain barrier. It spontaneously biotransforms to MTIC, the active metabolite of DTIC (dacarbazine) "and therefore should have few mechanisms available to allow cells to develop resistance," 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 the study for at least six months. The median time from radiotherapy to relapse for 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 had received prior chemotherapy and 200 mg/m² for those with no prior chemotherapy, given for five consecutive days, every 28 days. Evaluation was every two months with gadolinium-enhanced MRI.
Myelosuppression was tolerable, Dr. Levin said, and nonhematologic adverse effects, 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 number of patients were not evaluable because of incorrect histology. Of the 100 patients in this analysis, 59 actually had a diagnosis of anaplastic astrocytoma and were evaluable. However, all 100 patients were evaluated in this intent-to-treat study.
Overall, 41% of patients had an objective response, and 25% had stable disease. "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-treat analysis and 51% among those with diagnosed anaplastic astrocytoma. One-year event-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 modified brain cancer module. "As you would intuitively expect, patients who respond 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 life over the course of the study.
"The study is encouraging because there are few treatments now available for this very aggressive type of brain tumor," Dr. Levin said. "The patients in the study tolerated the drug well, with no negative impact on their quality of life."