Pharmacoepidemiology of myelotoxicity (TOX) with temozolomide (TMZ) in malignant glioma patients

9548 Background: A benefit of temozolomide (TMZ) is that myelosuppression (TOX) is uncommon. Recently, several small series report significant TOX resulting in treatment delays or even death in malignant glioma (MG) patients. The ability to predict individual patient risk of TOX may allow for more individualized dosing and management. Methods: A retrospective review of all MG patients treated at M. D. Anderson Cancer Center between 12/97 and 12/04 was completed. Incidence of TOX during the first cycle of TMZ and association with clinical variables was assessed by univariate analysis. A clinical risk formula for each gender was then developed by logistic regression using those factors with an alpha of ≤0.25. Results: In 680 patients with complete data, women were more likely to experience Grade 3 or 4 TOX than men (18% vs 7% p=0.015). The clinical risk formula was then developed. Age remained in each clinical risk formula because of observable trends and clinical significance for males >40 and females 31–40. For males, other factors which increased risk included: Body Surface Area (BSA) ≥2; white blood count ≤6.5; not on steroids; and being on bowel medication (MED) or thyroid replacement (p=0.0001). For females, final factors are: no prior chemotherapy; creatinine ≥1; platelet count < 270,000; BSA < 2; not on anxiety or reflux MED; and being on bowel or pain MED (p<0.0001). The final variables are given a score of 1 if present and are added for a final score with associated risk of TOX. Based on the number of factors present, risk of TOX ranged from 0% for a score of 0–1 (males) and 0–3 (females) to as high as 33% (male score of 5) and 80% (female score of 7). Conclusions: TOX is uncommon with TMZ, but may be significant for those at risk. Use of a clinical model to predict risk may allow for individualized dosing and management. As has been previously reported (Scheurer et al, AACR 2008), a subset of these patients also had evaluation of polymorphisms (SNPs) in DNA repair and xenobiotic metabolism analyzed. Three SNPs were associated with risk for TOX., NQ01 and GSTP1 decreased risk by 70% and 72%, whereas alterations in MGMT resulted in a 2.4-fold increase in risk. The association between the clinical risk factors for TOX and genetic effects will be further explored in a larger sample. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough Schering-Plough