Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors

¹ Department of Integrative Nursing Care, University of Texas Health Science Center at Houston-School of Nursing, Houston, TX; Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX; 6901 Bertner Ave., Houston, TX 77030, USA
² Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, TX
³ Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
⁴ Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX
⁵ Texas Children’s Cancer Center, Baylor College of Medicine, Houston, TX, USA

^* To whom correspondence should be addressed. E-mail: Terri.S.Armstrong{at}uth.tmc.edu.

	Abstract

A benefit of Temozolomide (TMZ) is that myelotoxicity (TOX) is uncommon. Recently, several small series report significant TOX resulting in treatment delays or death. The ability to predict risk of TOX may influence patient care. A retrospective review of 680 malignant glioma patients was completed. A clinical risk formula for TOX for each gender was developed by logistic regression. The variables which remained are assigned a score of 1 and are added together for a final risk score. Women experienced more TOX then men (p=0.015). For males, risk factors include: BSA >=2 (OR 2.712, p=0.04); Not on steroids (OR 2.214, p=0.06); and on Bowel medication (meds) (OR 3.955, p=0.008). For females, final factors include: No prior chemotherapy (OR 3.727, p=0.001); Creatinine >=1 (OR 6.08 p=0.002); Platelet t < 270k (OR 2.438, p=0.03); BSA < 2 (OR 4.178, p=0.04); not on GERD meds (OR 2.942, p=0.01); and on analgesics (OR 2.169, p=0.05). Age was included because of observable trends. Risk of developing TOX ranged from 0% to 33% (male) and 100% (females). Polymorphisms in NQO1, MGMT, and GSTP1 were related to risk of developing TOX in a subset of patients. TOX with TMZ is a significant clinical issue for those at risk. Use of a clinical model to predict risk and evaluation of identified genetic polymorphisms related to TOX may allow for individualized dosing optimizing patient management.

Key Words: :brain tumors, myelotoxicity, chemotherapy

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