title: Managing reduced methotrexate clearance in a patient with a heterozygous methylenetetrahydrofolate reductase gene polymorphism.
abstract: High dose methotrexate has become one of the treatments of choice for patients with primary CNS lymphomas due to its ability to penetrate the blood-brain barrier. A potentially serious complication of this therapy is methotrexate-related nephrotoxicity. We report the case of a patient with a common genetic polymorphism that may have predisposed this patient experience clinically significant toxicity from systemic folate depletion. After the first cycle of chemotherapy that included high dose methotrexate, the patient's serum creatinine rose and the patient's methotrexate level remained above the toxic range for six days. On cycle two, the patient was treated with a 25% dose reduction in methotrexate and more aggressive hydration and alkalization. With this alteration in the regimen, the patient was able to receive six more cycles and had a complete radiographic tumor response in the brain and a disappearance of tumor cells in the CSF without any further renal complications. This case report illustrates the feasibility of administering high dose methotrexate with modifications as a treatment of choice in individuals with methylenetetrahydrofolate reductase gene mutations.
authors: Umass Memorial Medical Center -University Campus, Worcester, MA 01655, USA. gammond@ummhc.org
authors: David C
authors: DC
authors: Gammon
authors: Mansi S
authors: MS
authors: Bhatt
authors: Bhavini
authors: B
authors: Patel
authors: Meghan
authors: M
authors: Anderson
authors: Alixis
authors: A
authors: Van Horn
authors: Michael J
authors: MJ
authors: Glantz
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000931:Antidotes / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D016393:Lymphoma, B-Cell / Q000150:complications / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D000069283:Rituximab; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002955:Leucovorin; D008727:Methotrexate