[Untitled]

The Radiation Therapy Oncology Group enrolled 30 patientswith recurrent malignant astrocytomas onto a phase IIstudy (RTOG 91-13). Patients were treated with all-trans-retinoicacid at a starting dose of 120 mg/m2per day orally continuously until disease progression. Fourteenpatients had glioblastoma, 14 had anaplastic astrocytoma, and2 had other histologies; 53% were under 50years of age. All patients had failed radiationtherapy and/or at least one chemotherapy regimen. Allpatients had a Karnofsky performance status score ofat least 70, but only 37% had aKPS of 90-100. Forty percent had a neurologicfunction status of grade 1 (able to work).A minimum of 4 weeks of all-trans-retinoic aciddefined adequate treatment. Twenty-five patients received adequate therapy.Most common toxicities were dry skin, cheilitis, anemia,and headache; 3 patients had grade 3 headacherequiring suspension of all-trans-retinoic acid. No grade 3hematologic toxicity was observed. Of 25 adequately treatedpatients, 3 showed objective regression of tumor onmagnetic resonance imaging and computed tomography scans, 3patients remained stable, and 19 patients had diseaseprogression. The median time to tumor progression was3.8 months and the median survival time was5.7 months.This study suggests that this dose of singleagent all-trans-retinoic acid has modest clinical activity againstrecurrent malignant gliomas with tolerable side effects. Aresponse rate of 12% and a stabilization rateof 12% are lower than expected. Future studieswith higher dosage or in combination with biologicalresponse modifiers or chemotherapy may be warranted.