Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors.
A benefit of temozolomide (TMZ) is that myelotoxicity is uncommon. Recently, several small series have reported significant myelotoxicity resulting in treatment delays or death. The ability to predict risk of myelotoxicity may influence patient care. We retrospectively reviewed 680 malignant glioma patients and developed a clinical risk formula for myelotoxicity for each gender by logistic regression. The variables that remained were assigned a score of 1 and added together for a final risk score. Women experienced more myelotoxicity than did men (p = 0.015). For males, risk factors included body surface area (BSA) > or = 2 m(2) (odds ratio [OR] = 2.712, p = 0.04), not on steroids (OR = 2.214, p = 0.06), and on bowel medication (OR = 3.955, p = 0.008). For females, final factors included no prior chemotherapy (OR = 3.727, p = 0.001), creatinine > or = 1 mg/dl (OR = 6.08, p = 0.002), platelets < 270,000/mm(3) (OR = 2.438, p = 0.03), BSA < 2 m(2) (OR = 4.178, p = 0.04), not on medication for gastroesophageal reflux disease (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 myelotoxicity ranged from 0% to 33% (male) and from 0% to 100% (females). Polymorphisms in NQO1 (NAD(P)H dehydrogenase, quinone 1), MGMT (O(6)-methylguanine-DNA methyltransferase), and GSTP1 (glutathione S-transferase pi 1) were related to risk of developing myelotoxicity in a subset of patients. Myelotoxicity 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 myelotoxicity may allow for individualized dosing, optimizing patient management.
Armstrong
Terri S
TS
Department of Integrative Nursing Care, University of Texas Health Science Center at Houston, School of Nursing, Baylor College of Medicine; Houston, TX, USA.
Cao
Yumei
Y
Scheurer
Michael E
ME
Vera-Bolaños
Elizabeth
E
Manning
Rochelle
R
Okcu
Mehmet F
MF
Bondy
Melissa
M
Zhou
Renke
R
Gilbert
Mark R
MR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced* / Q000188:drug therapy; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D003606:Dacarbazine; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D019853:O(6)-Methylguanine-DNA Methyltransferase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D000077204:Temozolomide