ALL-TRANS-RETINOIC ACID - A PHASE-II RADIATION-THERAPY ONCOLOGY GROUP-STUDY (RTOG-91-13) IN PATIENTS WITH RECURRENT MALIGNANT ASTROCYTOMA

The Radiation Therapy Oncology Group enrolled 30 patients with recurre nt malignant astrocytomas onto a phase II study (RTOG 91-13). Patients were treated with all-trans-retinoic acid at a starting dose of 120 m g/m(2) per day orally continuously until disease progression. Fourteen patients had glioblastoma, 14 had anaplastic astrocytoma, and 2 had o ther histologies; 53% were under 50 years of age. All patients had fai led radiation therapy and/or at least one chemotherapy regimen. All pa tients had a Karnofsky performance status score of at least 70, but on ly 37% had a KPS of 90-100. Forty percent had a neurologic function st atus of grade 1 (able to work). A minimum of 4 weeks of all-trans-reti noic acid defined adequate treatment. Twenty-five patients received ad equate therapy. Most common toxicities were dry skin, cheilitis, anemi a, and headache; 3 patients had grade 3 headache requiring suspension of all-trans-retinoic acid. No grade 3 hematologic toxicity was observ ed. Of 25 adequately treated patients, 3 showed objective regression o f tumor on magnetic resonance imaging and computed tomography scans, 3 patients remained stable, and 19 patients had disease progression. Th e median time to tumor progression was 3.8 months and the median survi val time was 5.7 months. This study suggests that this dose of single agent all-trans-retinoic acid has modest clinical activity against rec urrent malignant gliomas with tolerable side effects. A response rate of 12% and a stabilization rate of 12% are lower than expected. Future studies with higher dosage or in combination with biological response modifiers or chemotherapy may be warranted.