Retinoids for glioblastoma – pro
Amnesteem is an isotretinoid approved for treatment of nodular acne. It is lipophilic and penetrates into the brain and there is interest in using it to treat brain tumors, including glioblastoma. The mechanisms through which this compound regulates intracellular processes has been extensively investigated. Clinical information about effectiveness of retinoids is less conclusive. Pilts et al found that the population-based effectiveness of temazolomide and cis-retinoic acid regimen is similar to the clinical trial efficacy of 6 months of adjuvant temazoloamide.
All-trans retinoic acid (ATRA), cis-retinoic acid, and fenretinide have been evaluated in clinical studies in patients with high-grade gliomas. ATRA was evaluated in 30 patients with recurrent high-grade glioma]. Although three patients had partial responses, the median time to tumor progression and survival were only 3.8 and 5.7 months, respectively. Cis-retinoic acid had modest activity in a phase II study of 80 patients with recurrent high-grade glioma]. The median progression-free and overall survival durations after treatment initiation were 10 and 25 weeks, respectively, while the six-month progression-free survival was 19 percent. Cis-retinoic acid has been combined with temozolomide both in patients with recurrent and primary high-grade gliomas, without evidence of a synergistic effect.
REFERENCES:
M Ying et al, Regulation of glioblastoma stem cells by retinoic acid: role for Notch
pathway inhibition. ONCOGENE 30(31):3454-67 · FEBRUARY 2011
M.W. Pitz etal, Extended adjuvant temozolomide with cis-retinoic acid for adult glioblastoma.Oncology Vol 19, No 6 (2012)
SJ, Levin VA, Yung WK, Hess KR, Groves MD, 3-cis-retinoic acid in the treatment of recurrent glioblastoma multiforme. Neuro Oncol. 2004;6(3):253.
Jaeckle KA, Hess KR, Yung WK, Greenberg H, Fine H, Schiff D, Pollack IF, Kuhn J, Fink K, Mehta M, Cloughesy T, Nicholas MK, Chang S, Prados M, North American Brain Tumor Consortium, Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study. J Clin Oncol. 2003;21(12):2305.
Puduvalli VK, Yung WK, Hess KR, Kuhn JG, Groves MD, Levin VA, Zwiebel J, Chang SM, Cloughesy TF, Junck L, Wen P, Lieberman F, Conrad CA, Gilbert MR, Meyers CA, Liu V, Mehta MP, Nicholas MK, Prados M, North American Brain Tumor Consortium, Phase II study of fenretinide (NSC 374551) in adults with recurrent malignant gliomas: A North American Brain Tumor Consortium study. J Clin Oncol. 2004;22(21):4282.