Renal impairment following the combined use of high-dose methotrexate and procarbazine

1988 ◽  
Vol 21 (3) ◽  
Author(s):  
P. Price ◽  
H. Thompson ◽  
E.M. Bessell ◽  
H.J.G. Bloom
Keyword(s):  
Renal Impairment ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Combined Use

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.

scholarly journals Methotrexate Associated Renal Impairment Is Related to Delayed Elimination of High-Dose Methotrexate

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shi-Long Yang ◽  
Fen-Ying Zhao ◽  
Hua Song ◽  
Di-Ying Shen ◽  
Xiao-Jun Xu
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Serum Creatinine ◽  
Lymphoblastic Leukemia ◽  
Serum Creatinine Concentration ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Creatinine Ratio ◽  
Creatinine Concentration ◽  
Dose Methotrexate

Although Methotrexate (MTX) is an effective drug for the treatment of acute lymphoblastic leukemia (ALL), the toxicity remains a significant problem. In this prospective study, fifty-four patients with ALL were enrolled. 3 g or 5 g MTX/m2was administered over 24 hours. Serum MTX concentrations were determined in 24, 48, and 96 hours after MTX infusion. Serum creatinine concentrations and creatinine clearance rate (CCR) were determined before and 24 and 48 hours after MTX infusion. A total of 173 courses of MTX infusion were administered. The serum creatinine concentrations did not change much after MTX infusion while the CCR was gradually decreased. MTX clearance status was independently related to CCR decrease, with the risk of 8.07 to develop renal impairment in patients with delayed MTX elimination. Serum creatinine concentration, serum creatinine ratio, CCR, and CCR ratio at 24 hours were all related to MTX elimination delay. Patients with serum creatinine level >35.0 μmol/L, creatinine ratio >1.129, or CCR <100.0 mL/min were more likely to undergo MTX elimination delay. In conclusion, MTX could induce transient renal impairment and compromised renal function will delay MTX clearance. The serum creatinine concentration and the ratio and CCR are useful tools for evaluating MTX elimination status.

High-dose methotrexate-induced reversible grade 4 hyperbilirubinaemia and transaminitis in an adolescent with Burkitt Leukaemia

2021 ◽  
Vol 14 (1) ◽  
pp. e237512
Author(s):  
Sanjeev Khera ◽  
Randhir Ranjan ◽  
Sateesh Ramachandran ◽  
Ajay Beriwal
Keyword(s):  
Liver Injury ◽  
Clinical Significance ◽  
Short Latency ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Drug Induced ◽  
Common Cause ◽  
Drug Induced Liver Injury ◽  
Dose Methotrexate

Symptomatic drug-induced liver injury (DILI) is an uncommon problem. Direct DILI is dose-related, predictable with short latency (hour to days) and is generally associated with transient and reversible transaminitis without jaundice. Antimetabolites including methotrexate are a common cause for direct DILI. Hepatotoxicity associated with high-dose methotrexate (HD-MTX) is generally transient and includes reversible elevation of transaminase in up to 60% and associated hyperbilirubinaemia (≤grade 2) in 25% of courses and therefore is of no clinical significance. Severe grades of DILI with HD-MTX (grade ≥4) are extremely rare. We describe an adolescent with Burkitt leukaemia who had reversible grade 4 DILI including hyperbilirubinaemia postfirst course of HD-MTX. Rechallenge with two-third dose of HD-MTX in subsequent chemotherapeutic cycle did not cause recurrence of DILI.

scholarly journals Reduced dose folinic acid rescue after rapid high-dose methotrexate clearance is not associated with increased toxicity in a pediatric cohort

2021 ◽  
Author(s):  
Riitta Niinimäki ◽  
Henri Aarnivala ◽  
Joanna Banerjee ◽  
Tytti Pokka ◽  
Kaisa Vepsäläinen ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Optimal Dosage ◽  
High Dose Methotrexate ◽  
Reduced Dose ◽  
Dose Methotrexate ◽  
Antileukemic Effect ◽  
Folinic Acid Rescue ◽  
High Doses

Abstract Purpose Low doses of folinic acid (FA) rescue after high-dose methotrexate (HD-MTX) have been associated with increased toxicity, whereas high doses may be related to a decreased antileukemic effect. The optimal dosage and duration of FA rescue remain controversial. This study was designed to investigate, whether a shorter duration of FA rescue in the setting of rapid HD-MTX clearance is associated with increased toxicity. Methods We reviewed the files of 44 children receiving a total of 350 HD-MTX courses during treatment for acute lymphoblastic leukemia according to the NOPHO ALL-2000 protocol. Following a 5 g/m2 HD-MTX infusion, pharmacokinetically guided FA rescue commenced at hour 42. As per local guidelines, the patients received only one or two 15 mg/m2 doses of FA in the case of rapid MTX clearance (serum MTX ≤ 0.2 μmol/L at hour 42 or hour 48, respectively). Data on MTX clearance, FA dosing, inpatient time, and toxicities were collected. Results Rapid MTX clearance was observed in 181 courses (51.7%). There was no difference in the steady-state MTX concentration, nephrotoxicity, hepatotoxicity, neutropenic fever, or neurotoxicity between courses followed by rapid MTX clearance and those without. One or two doses of FA after rapid MTX clearance resulted in a 7.8-h shorter inpatient time than if a minimum of three doses of FA would have been given. Conclusion A pharmacokinetically guided FA rescue of one or two 15 mg/m2 doses of FA following HD-MTX courses with rapid MTX clearance results in a shorter hospitalization without an increase in toxic effects.

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