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13-cis-Retinoic acid in the treatment of recurrent glioblastoma multiforme

Departments of Neuro-Oncology (S.-J.S., V.A.L., W.-K.A.Y., M.D.G.) and Biostatistics (K.R.H.), University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA

¹ Address correspondence to Morris D. Groves, Department of Neuro-Oncology, Box 431, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA (mgroves{at}mdanderson.org).

Abstract

Basic science and clinical investigations have demonstrated that 13-cis-retinoic acid (cRA) has activity against malignant gliomas. To assess its effectiveness in the setting of recurrent glioblastoma multiforme (GBM), we performed a retrospective analysis of the medical records and neuroimaging results of patients with recurrent GBM who were treated with cRA. The toxicity profile of cRA, response, and effect on progression-free survival from initiation of treatment were end points of our analysis. Eighty-two of 85 patients with a median age of 51 years received at least 1 full cycle of cRA. At the initiation of cRA treatment, the median Karnofsky performance score was 80. All patients had failed conventional radiotherapy. Seven patients were chemonaïve, whereas 75 patients had received some form of chemotherapy. Radiographic partial responses, minor responses, and stable disease were seen in 4%, 8%, and 34% of patients, respectively. Two patients were not assessable. Progression-free survival and overall survival after initiation of cRA were 10.0 and 24.6 weeks, respectively. Six-month progression-free survival was 19% for the entire group. Grade 3 or 4 toxicity developed in 14 patients (16%), one of whom developed pancreatitis and died. The results of this study demonstrate only modest efficacy for cRA therapy in this cohort of heavily pretreated patients with recurrent GBM. This data supports the use of cRA in such patients, but its further evaluation in larger, prospective, controlled studies with or without other noncytotoxic and cytotoxic agents may be warranted.

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