Phase II trial of Gliadel plus O 6 -benzylguanic (O 6 -BG) for patients with recurrent glioblastoma multiforme

• Published in: Journal of clinical oncology Vol. 25; no. 18_suppl; p. 2036
• Main Authors: Quinn, J. A., Vredenburgh, J. J., Rich, J. N., Reardon, D. A., Desjardins, A., Gururangan, S., Friedman, A. H., Carter, J. H., Threatt, S., Friedman, H. S.
• Format: Journal Article
• Language: English
• Published: 20.06.2007
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2007.25.18_suppl.2036

Abstract only 2036 Background: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O 6 -alkylguanine-DNA alkyltransferase (AGT) which removes chloroethylation or methylation damage from the O 6 - position of guanine. O 6 -BG is an AGT substrate that inhibits AGT by suicide inactivation. A previous phase III randomized, placebo- controlled trial has shown that Gliadel wafer (G) significantly prolongs 6-month survival (55.5% for G vs. 35.6% for placebo) and median survival (28 weeks for G vs. 20 weeks for placebo) in patients with recurrent glioblastoma multiforme (GBM) (Brem et al 1995). Despite the success of G in prolonging survival we may be able to improve on this success by depleting AGT. Methods: Thus, we have designed a phase 2 trial where we define the activity and the toxicity of G in combination with a 5-day infusion of O 6 -BG in patients with recurrent GBM. In a prior study the O 6 -BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m 2 over 1 hour followed by a continuous infusion of 30 mg/m 2 /d for 48 hours. In order to guarantee depletion of tumor AGT activity for at least 5 days after G placement, this O 6 -BG bolus was repeated on days 3 and 5 while continuing the infusion. Results: To date, 47 patients have been enrolled out of a planned accrual of 50 patients. The 6-month survival is 80% and the median survival is 47 weeks. The adverse events include the following: 3 episodes of grade 3 CSF leak (6%), 7 episodes of grade 3 wound infection at craniotomy site (15%), 6 episodes of hyponatremia (13%), 3 episodes of hydrocephalus (6%), 1 episode of hygroma (2%), 1 episode of infectious meningitis (2%), 1 episode of arachnoiditis (2%), 1 episode of grade 3 fever (2%). Conclusions: Thus far, this data demonstrates an increase in the efficacy of G when combined with O 6 -BG. Three additional patients will be enrolled for a total accrual of 50 patients. [Table: see text]