Clinical Pharmacy Services Publications


Managing reduced methotrexate clearance in a patient with a heterozygous methylenetetrahydrofolate reductase gene polymorphism

UMMS Affiliation

Department of Pharmacy



Document Type


Medical Subject Headings

Antibodies, Monoclonal; Antidotes; Antimetabolites, Antineoplastic; dosage; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Humans; Leucovorin; Lymphoma, B-Cell; Male; Methotrexate; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Polymorphism, Genetic


Pharmacy and Pharmaceutical Sciences


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.

Rights and Permissions

Citation: J Oncol Pharm Pract. 2008 Sep;14(3):153-6. Link to article on publisher's site

Related Resources

Link to Article in PubMed