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

Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners
David C GammonMichael J Glantz

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.

References

Apr 29, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M J GlantzM J Egorin
Oct 3, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M J GlantzS B Howell
Jun 8, 2002·Pharmacogenomics·Cornelia M UlrichRachel Sparks
Mar 15, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tracy BatchelorRegina Priet
Nov 5, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hendrik PelsUwe Schlegel
Oct 22, 2004·Seminars in Oncology·Lisa M Deangelis, Adília Hormigo
Mar 10, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tracy Batchelor, Jay S Loeffler

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