title: Methotrexate elimination and toxicity: MTHFR 677C>T polymorphism in patients with primary CNS lymphoma treated with high-dose methotrexate.
abstract: The genetic association of the methylenetetrahydrofolate reductase gene (MTHFR) 677C>T polymorphism with methotrexate (MTX)-associated toxicity has been evaluated and conflicting results have been reported. The substantial heterogeneity of the studied population was suggested to be a possible explanation because ethnicity, MTX dose, coadministered chemotherapeutic agents, and folinate rescue dosage regimen could alter the MTX toxicity profile. The patient population was homogenized by limiting the cancer type to primary central nervous system lymphoma and chemotherapy protocol to a high-dose MTX monotherapy regimen. A total of 111 patients with 402 chemotherapy courses were analyzed. MTHFR 677C>T polymorphism was identified as an independent predictive marker for MTX-associated hematologic toxicity (odds ratio, 2.60; 95% confidence interval, 1.32-5.09; P = .0055). Clinically significant nephrotoxicity occurred in patients without delayed elimination, suggesting roles for factors other than serum MTX levels. MTX-induced hepatotoxicity and oral mucositis occurred independently of plasma MTX levels.
authors: Clinical Trial Center, Asan Medical Center, Seoul, Republic of Korea.|College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Gyeonggi, South Korea.
authors: Yun Jung
authors: YJ
authors: Choi
authors: Department of Pharmacy, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Hyangmin
authors: H
authors: Park
authors: Clinical Research Center, Asan Medical Center, Seoul, Republic of Korea.
authors: Ji Sung
authors: JS
authors: Lee
authors: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Gyeonggi, South Korea.
authors: Ju-Yeon
authors: JY
authors: Lee
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Shin
authors: S
authors: Kim
authors: Clinical Research Center, Asan Medical Center, Seoul, Republic of Korea.|Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Tae Won
authors: TW
authors: Kim
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Jung Sun
authors: JS
authors: Park
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Jeong Eun
authors: JE
authors: Kim
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Dok Hyun
authors: DH
authors: Yoon
authors: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Cheolwon
authors: C
authors: Suh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000633:toxicity*; D016543:Central Nervous System Neoplasms / Q000150:complications* / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000633:toxicity*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate
keywords: MTHFR 677C>T polymorphism; high-dose methotrexate; toxicity