This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Flombaum, C. D. Articles by Meyers, P. A. Search for Related Content PubMed PubMed Citation Articles by Flombaum, C. D. Articles by Meyers, P. A. Social Bookmarking                            What's this?

High-Dose Leucovorin as Sole Therapy for Methotrexate Toxicity

From the Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to Carlos D. Flombaum, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.

PURPOSE: Hemodialysis, hemoperfusion, thymidine, and carboxypeptidase have been recommended together with high-dose (HD) leucovorin (LV) to treat patients at risk for methotrexate (MTX) toxicity. To elucidate the efficacy of high LV rescue as the sole salvage modality for severe MTX intoxication, we studied 13 patients who were treated in this fashion at Memorial Sloan-Kettering Cancer Center (New York, NY).

PATIENTS AND METHODS: To identify patients at high risk for severe MTX toxicity, we performed a retrospective review of all patients with MTX levels greater than 100 µmol/L at 24 hours and greater than 10 µmol/L at 48 hours after HD MTX.

RESULTS: A total of 13 patients were identified. The median MTX concentration was 164 µmol/L at 24 hours (range, 102 to 940 µmol/L), 16.3 µmol/L at 48 hours (range, 10.5 to 190 µmol/L), and 6.2 µmol/L at 72 hours (range, 1.35 to 39 µmol/L). MTX levels remained greater than 0.1 µmol/L for an average of 11 ± 3 days (mean ± SD) (range, 7 to 17 days). In addition to supportive treatment with hydration and sodium bicarbonate administration, all patients were treated solely with HD LV, which was started within the first 24 hours in nine patients, 48 hours in three patients, and 72 hours in one patient in doses that varied from 0.24 to 8 g/d. Significant neutropenia (neutrophil count < 1,000/µL) occurred in eight patients and lasted for 1 to 5 days. Thrombocytopenia (platelet count < 100,000/µL) occurred in seven patients and lasted for 5 to 10 days. Other toxic manifestations included mucositis of varying degrees, diarrhea, and neutropenic fever, but all patients recovered.

CONCLUSION: In the range of MTX levels observed, HD LV can be used as a sole therapy for MTX toxicity without the need for extracorporeal removal and with tolerable morbidity.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. W. Smith Chiral Toxicology: It's the Same Thing...Only Different Toxicol. Sci., July 1, 2009; 110(1): 4 - 30. [Abstract] [Full Text] [PDF]

				R. L. Snyder Resumption of high-dose methotrexate after methotrexate-induced nephrotoxicity and carboxypeptidase G2 use Am. J. Health Syst. Pharm., June 1, 2007; 64(11): 1163 - 1169. [Abstract] [Full Text] [PDF]

				B. C. Widemann and P. C. Adamson Understanding and managing methotrexate nephrotoxicity. Oncologist, June 1, 2006; 11(6): 694 - 703. [Abstract] [Full Text] [PDF]

				S. Suresh, S. Lozono, and S. C. Hall Large-Dose Intravenous Methotrexate-Induced Cutaneous Toxicity: Can Oral Magnesium Oxide Reduce Pain? Anesth. Analg., May 1, 2003; 96(5): 1413 - 1414. [Abstract] [Full Text] [PDF]

				J. M. Sweet and C. P. Holstege Bone Marrow Failure From Medication Error: Diagnosis by History, Not Biopsy Arch Intern Med, August 13, 2001; 161(15): 1911 - 1912. [Full Text] [PDF]