NDLI: Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study.

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Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lombardi, Giuseppe Rumiato, Enrica Bertorelle, Roberta Saggioro, Daniela Farina, Patrizia Della Puppa, Alessandro Zustovich, Fable Berti, Franco Sacchetto, Valeria Marcato, Raffaella Amadori, Alberto Zagonel, Vittorina
Description	Country affiliation: Italy Author Affiliation: Lombardi G ( *Medical Oncology 1 Molecular Immunology and Oncology §Radiotherapy and Nuclear Medicine Unit, Veneto Institute of Oncology - IRCCS Neurosurgery Department, Azienda Ospedale â¥Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.)
Abstract	BACKGROUND: Temozolomide (TMZ) administered daily with radiation therapy (RT) for 6 weeks, followed by adjuvant TMZ for 6 cycles, is the standard therapy for newly diagnosed glioblastoma (GBM) patients. Although TMZ is considered to be a safe drug, it has been demonstrated to cause severe myelotoxicity; in particular, some case reports and small series studies have reported severe myelotoxicity developing during TMZ and concomitant RT. We performed a prospective study to analyze the incidence of early severe myelotoxicity and its possible clinical and genetic factors. PATIENTS AND METHODS: From November 2010 to July 2012, newly diagnosed GBM patients were enrolled. They were eligible for the study if they met the following criteria: pathologically proven GBM, age 18 years and older, an Eastern Cooperative Oncology Group performance status of 0 to 2, adequate renal and hepatic function, and adequate blood cell counts before starting TMZ plus RT. Grading of hematologic toxicity developing during radiation and TMZ was based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Clinical factors from all patients were recorded. The methylation status and polymorphic variants of O-methylguanine-DNAmethyl-transferase gene in peripheral blood mononuclear cells, and polymorphic genetic variants of genes involved in the pharmacokinetics and pharmacodynamics of TMZ, were analyzed. For genetic analyses, patients with toxicity were matched (1:2) for age, performance status, anticonvulsants, and proton pump inhibitors with patients without myelotoxicity. RESULTS: We enrolled 87 consecutive GBM patients: 32 women and 55 men; the average age was 60 years. During TMZ and RT, 4 patients (5%) showed grade 3-4 myelotoxicity, and its median duration was 255 days. Predictor factors of severe myelotoxicity were female sex, pretreatment platelet count of ≤3,00,000/mm, methylated O-methylguanine-DNA methyltransferase promoter in the hematopoietic cell system, and specific polymorphic variants of the cytochrome P450 oxidoreductase and methionine adenosyltransferase 1A genes. CONCLUSIONS: Although we studied a small population, we suggest that both clinical and genetic factors might simultaneously be associated with severe myelosuppression developed during TMZ plus RT. However, our results deserve validation in larger prospective studies and, if the factors associated with severe myelotoxicity are validated, dose adjustments of TMZ for those patients may reduce the risk of severe myelotoxicity during the concomitant treatment.
File Format	HTM / HTML
ISSN	02773732
Issue Number	5
Volume Number	38
e-ISSN	1537453X
Journal	American Journal of Clinical Oncology
Language	English
Publisher	Lippincott Williams & Wilkins
Publisher Date	2015-10-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Oncology Brain Neoplasms Drug Therapy Radiotherapy Chemoradiotherapy Adverse Effects Dna Modification Methylases Genetics Dna Repair Enzymes Dacarbazine Analogs & Derivatives Glioblastoma Tumor Suppressor Proteins Adult Aged Anticonvulsants Therapeutic Use Antineoplastic Agents, Alkylating Pharmacokinetics Female Hematologic Diseases Chemically Induced Humans Leukocytes, Mononuclear Drug Effects Radiation Effects Male Middle Aged Polymorphism, Single Nucleotide Prospective Studies Proton Pump Inhibitors Controlled Clinical Trial Journal Article
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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