Not many options are available for progressive gliomas. Among them is Accutane, studied most in combination with temazolamide. A phase II trial (Radiation Therapy Oncology Group 91–13) of all-trans-retinoic acid in 30 patients with recurrent malignant glioma disclosed minor activity, with tolerable side effects; a response rate of 12% was observed, with a median time to progression of 3.8 months and a median OS of 5.7 months. A similar single-institution phase II trial of all-trans-retinoic acid in 36 patients with recurrent glioma did not show much evidence of activity, with a 3% minor response rate, and median time to progression of only 8 weeks. A recent phase II trial of the combination of radiotherapy and cRA plus interferon alfa-2a in patients with newly diagnosed high-grade glioma did not show an improvement in survival as compared with historical controls. Yung et al conducted a phase II prospective study of 43 patients with recurrent malignant glioma treated with cRA as a single agent, administered at a daily oral dose of 60 to 100 mg/m2/d for 3 weeks, followed by 1 week of rest every 28 days. A response rate of 23% (PR, 7%; minor response, 16%) was observed, with median time to progression of 16 weeks and median survival of 58 weeks for GM and 34 weeks for AA. In another study, for all patients, the PFS 6 was 43%. PFS 6 was 32% for GM and 50% for all AG combined (46% for the non-AO AG subset and 61% for pure AO subset). These results, as compared with the PFS 6 observed in the database (GM, 15%; AG, 31%), met the criteria for PFS 6 success, exceeding the 20% improvement for both the GM and AG strata. At the time of design of the current protocol, the PFS 6 for TMZ alone was not yet reported; subsequent clinical trials of single-agent TMZ reported a PFS 6 of 21% for GM and 44% for AA.
Kurt A. Jaeckle, Kenneth R. Hess, W.K. Alfred Yung, Harry Greenberg, Howard Fine, David Schiff, Ian F. Pollack, John Kuhn, Karen Fink, Minesh Mehta, Timothy Cloughesy, M. Kelly Nicholas, Susan Chang, Michael Prados Journal of Clinical Oncology, Vol 21, Issue 12 (June), 2003: 2305-2311
Groves, M. D., et al. Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme. Journal of Clinical Oncology, 2002, 20, 1383-1388