High-dose leucovorin as sole therapy for methotrexate toxicity Journal Article


Authors: Flombaum, C. D.; Meyers, P. A.
Article Title: High-dose leucovorin as sole therapy for methotrexate toxicity
Abstract: 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 far MTX toxicity without the need for extracorporeal removal and with tolerable morbidity.
Keywords: osteosarcoma; adolescent; adult; child; treatment outcome; aged; bone neoplasms; retrospective studies; drug tolerability; neutropenia; drug efficacy; methotrexate; antimetabolites, antineoplastic; thrombocytopenia; drug administration schedule; creatinine; kidney failure; kidney; folinic acid; folic acid antagonists; hemodialysis; leucovorin; urinary excretion; drug intoxication; antidotes; peritoneal dialysis; humans; human; female; priority journal; article; hemoperfusion
Journal Title: Journal of Clinical Oncology
Volume: 17
Issue: 5
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1999-04-01
Start Page: 1589
End Page: 1594
Language: English
PUBMED: 10334548
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 16 August 2016 -- Source: Scopus