TREATMENT OF RECURRENT MALIGNANT GLIOMAS WITH HIGH-DOSE 13-CIS-RETINOIC ACID

Malignant gliomas account for more than 60% of all primary brain tumor s in adults, Adjuvant chemotherapy in addition to radical surgery and radiation therapy has provided only a modest increase in survival, Ret inoic acid has been shown to have growth-inhibitory activity against g lioma cells in culture, This provides the rationale for a Phase II stu dy using 13-cis-retinoic acid (CRA) in patients with recurrent maligna nt brain tumors, The objective of this study was to determine the clin ical activity of CRA in patients with a histologically proven diagnosi s of malignant brain tumor and documented progressive or recurrent dis ease after radiation and chemotherapy, Fifty patients with documented recurrent disease were treated with CRA as a single agent p.o. at a do se of 60-100 mg/m(2) per day, Three weeks of treatment were followed b y 1 week of rest, Of the 43 patients who received more than 4 weeks of therapy, 3 (7%) achieved partial response, 7 (16%) achieved minor res ponse, 13 (30%) remained stable, and 20 (47%) had disease progression, The median time from onset of treatment to disease progression for th e whole group of 43 patients was 16 weeks (19 weeks for glioblastomas and 11 weeks for anaplastic glioma), whereas that for the 23 patients with partial response and minor response and who remained stable was 6 6 weeks, and that for the 20 patients with progressive disease was onl y 8 weeks. The median survival time for glioblastoma was 58 weeks, and 34 weeks for anaplastic astrocytoma, Toxicity was mainly dermatologic al, with dry skin and cheilitis, These preliminary results suggest tha t 13-cis-retinoic acid is active against malignant gliomas and is very well tolerated.