scholarly journals Evaluation, Identification, and Management of Acute Methotrexate Toxicity in High-dose Methotrexate Administration in Hematologic Malignancies

Cureus ◽  
2018 ◽  
Author(s):  
Doron Feinsilber ◽  
Roberto J Leoni ◽  
Duminda Siripala ◽  
Julianne Leuck ◽  
Katrina A Mears
Keyword(s):  
Hematologic Malignancies ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Methotrexate Toxicity

Re-challenge with High Dose Methotrexate vs. Reduced Dose After Methotrexate Toxicity in Pediatric Osteosarcoma:Case Report

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Walid Ibrahim ◽  
Alam Alhuda Mohamed ◽  
Nawaf Alkhayat ◽  
Yasser Elborai
Keyword(s):  
Renal Impairment ◽  
Supportive Care ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Reduced Dose ◽  
Dose Methotrexate ◽  
Methotrexate Toxicity ◽  
Renal Complications ◽  
Leucovorin Rescue ◽  
Pediatric Osteosarcoma

Introduction: Methotrexate (MTX), a classic antifolate, is one of the most widely used and well-studied anticancer agents. High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is one of the standard therapies for osteosarcoma. High-dose methotrexate (HDMTX) can exert significant toxicity and requires complex pharmacokinetic monitoring and leucovorin rescue. The side effect profile of MTX varies markedly according to the dose. Regimens containing MTX are classified as high, intermediate, or low-dose. High-dose methotrexate (HD-MTX; 12 g/m2) is a part of the golden standard therapy for pediatric osteosarcoma (OS). Risk factors associated with MTX toxicity in children with OS are not well defined. Case Presentation: We report here a case of pediatric osteosarcoma with nephrotoxicity associated with delayed MTX excretion who was successfully managed using supportive measures that encouraged us to re-challenge with a full dose of MTX then we reduced the dose to 50% to attain the final critical decision about continuation or changing the regimen of treatment for the patient. Our patient developed moderate renal complications during therapy that improved with supportive care, so we challenged with more cycles of a high dose MTX, but the patient developed serious renal complications. A reduced dose of MTX with 50% was given successfully without any renal impairment. Conclusion: Methotrexate toxicity that might not occur during the initial courses of high-dose MTX is not a predictive of the tolerability of further courses and re-challenging with HDMTX is risky, but reduced dose methotrexate is a good option rather than changing the regimen, with good tolerability and rapid clearance of HDMTX. HDMTX-induced renal impairment occurs in a low percentage of patients with osteosarcoma and can be managed successfully by maximum supportive care. MTX clearance can be affected by gender and age.

Modulation of high-dose methotrexate toxicity by a non-toxic level of 5-fluorouracil

Toxicology ◽  
1986 ◽  
Vol 41 (1) ◽  
pp. 61-73 ◽  
Author(s):  
Terry J. Robbins ◽  
Donnell Bowen ◽  
Quang Q. Bui ◽  
Minh-Tam Tran
Keyword(s):  
High Dose ◽  
High Dose Methotrexate ◽  
Toxic Level ◽  
Dose Methotrexate ◽  
Methotrexate Toxicity

scholarly journals Effect of Levetiracetam on Time to High‐Dose Methotrexate Clearance in Patients With Hematologic Malignancies

2019 ◽  
Vol 60 (3) ◽  
pp. 324-330
Author(s):  
Uvette Lou ◽  
Jamie Kwok ◽  
Thu Anne Nguyen ◽  
Allen Zhou ◽  
Samantha O. Luk
Keyword(s):  
Hematologic Malignancies ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

scholarly journals High-dose methotrexate toxicity in elderly patients with primary central nervous system lymphoma

2005 ◽  
Vol 16 (3) ◽  
pp. 445-449 ◽  
Author(s):  
K. Jahnke ◽  
A. Korfel ◽  
P. Martus ◽  
M. Weller ◽  
U. Herrlinger ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Central Nervous System Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Methotrexate Toxicity

scholarly journals Pharmacokinetic analysis of high-dose methotrexate treatments in children with hematologic malignancies

2011 ◽  
Vol 152 (40) ◽  
pp. 1609-1617
Author(s):  
Katalin Csordás ◽  
Olivér Eipel ◽  
Márta Hegyi ◽  
Monika Csóka ◽  
Éva Pap ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Serum Levels ◽  
Hematologic Malignancies ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Serum Concentrations ◽  
Toxicity Evaluation ◽  
Dose Methotrexate

Monitoring the pharmacokinetic parameters of different anticancer drugs is necessary because they might have several side effects. Aim: Pharmacokinetic and toxicity evaluation of high-dose methotrexate treatments in children with acute lymphoblastic leukemia. Patients and methods: 43 children (28 boys, 15 girls, mean age: 7.03 years) in 147 cases were treated with 5 g/m2/24h MTX according to ALL-BFM 1995 and 2002 protocols. Methotrexate and 7-hydroxi-methotrexate levels were measured with high pressure liquid chromatography at 24, 36, 48 hours. Authors registered the development of hepatotoxicity, nephrotoxicity, grade III/IV oral mucositis. Results: Therapeutic methotrexate serum concentrations (30-100µmol/l) were achieved in 72.5% of the cases. Repeated treatments resulted similar serum levels. Hepatotoxicity and hypoproteinemia occurred in 17% and in 48.9% of the cases. There was significant correlation between serum 7-hydroxi-methotrexate and creatinine levels (p<0.05). Conclusion: 5 g/m2methotrexate resulted reliable therapeutic serum levels with mild and reversible toxicity. 7-hydroxi-methotexate measurements might be more useful than methotrexate levels to detect toxicity. Orv. Hetil., 2011, 152, 1609–1617.

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