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BACKGROUND Despite the growing body of evidence demonstrating an increased clinical benefit of alkylating agents in glioblastoma patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, little is known regarding the effect of MGMT status on toxicity. The purpose of this investigation is to provide insight into the potential association between MGMT promoter methylation and the development of Grade 3/4 hematologic toxicities in patients receiving temozolomide. METHODS A total of 63 patients with documented glioblastoma or anaplastic astrocytoma diagnoses were evaluated retrospectively. A chi-square test of independence was utilized to evaluate the incidence of hematologic toxicities and patient overall survival was determined by univariate analysis estimated through use of Kaplan-Meier curves. Relative frequencies of treatment discontinuation secondary to myelosuppression were also compared. RESULTS At the time of study completion, 71.4% of patients with MGMT promoter hypermethylation had survived compared with 50% of patients with hypomethylation (HR 0.86; 95% CI 0.71 to 1.05; P&amp;gt;0.05). The percentage of patients who experienced Grade 3/4 hematologic toxicities during concurrent treatment was 20% and 5.1% within the hypermethylated and hypomethylated groups, respectively, and 26.7% and 17.9% throughout standard therapy. While a statistical difference was not found between the cumulative incidences of Grade 3/4 hematologic toxicity events throughout both phases of treatment, a statistical difference was noted in the incidence of Grade 4 occurrences with ten events occurring in the hypermethylated group and zero in those with hypomethylated promoter regions (P&amp;lt; 0.01). Furthermore, use of temozolomide in hypermethylated patients resulted in fewer completed cycles of standard therapy and higher rates of treatment delays and drug discontinuation. CONCLUSIONS This study showed marked differences in the frequency of temozolomide-induced hematologic toxicities and treatment discontinuation based on tumor MGMT promoter methylation status. Further research is warranted in larger patient populations to both validate and determine the clinical significance of these findings.

neuro-oncology

NCOG-29. O6-METHYLGUANINE DNA METHYLTRANSFERASE (MGMT) PROMOTER METHYLATION STATUS AND THE INCIDENCE OF TEMOZOLOMIDE-INDUCED HEMATOLOGIC TOXICITY: AN ASSOCIATION STUDY