Two Pediatric Osteosarcoma Cases with Delayed Methotrexate Excretion: Its Clinical Course and Management

Lee, Kangmin; Lee, Hee Woo; Kim, Seung‐Yeon; Lee, Hyeon Jeong; Kim, Dong Hwan; Cho, Joongbum; Kim, Dong Ho; Lim, Jung Sub; Lee, Jin Kyung; Lee, Jun Ah

doi:10.4143/crt.2011.43.1.67

Cited by 4 publications

(3 citation statements)

References 15 publications

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“… 9 More important, delayed MTX excretion may occur in the absence of any predisposing factor. 6 In this case, the girl suffered from “severe” delayed excretion (C 24 h >50 μmol/L) and acute liver and kidney injury. She was successfully managed using supportive cares and CVVHDF.…”

Section: Discussionmentioning

confidence: 91%

“… 5 Factors including age, hydration status and the concurrent use of nephrotoxic agents are shown to influence MTX clearance. 6 Furthermore, recent pharmacogenetic studies have investigated the effects of several genes and polymorphisms on MTX clearance, 7 , 8 which may help us to better understand the pharmacokinetic variability and improve patient outcomes.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Single Nucleotide Polymorphisms in Transporter Proteins and the Folate Metabolism Pathway in Delayed Methotrexate Excretion: A Case Report and Literature Review

Wang¹,

Zhao²,

Sun³

et al. 2022

PGPM

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High-dose methotrexate (HDMTX) is a pivotal component of the chemotherapeutic regimens of osteosarcoma. However, the use of HDMTX is limited by an increased risk of dose-dependent toxicity. It is thought that the plasma levels and therapy-related toxicity of MTX could be associated with single nucleotide polymorphisms (SNPs) within MTX metabolism pathway genes. Here, we report a case of a paediatric osteosarcoma girl with delayed MTX excretion who was successfully managed using supportive measures and continuous veno-venous haemodiafiltration. We further identified the cause that could account for delayed elimination by genotyping analysis. The results showed that variations have been found in SLCO1B1, SLC19A1, ABCB1 and MTHFR , all those were reported to have a strong association with delayed elimination of MTX in clinical studies. After comprehensive consideration of genotype and clinical phenotype, the second course of HDMTX was administered to this patient at a half reduced dose. We also performed a literature review to summarize the pharmacogenetic factors that influence HDMTX pharmacokinetics or MTX-related adverse effects in osteosarcoma patients. It is suggested that the potential risk of delayed MTX elimination is worthy of clinical attention, and the implementation of genotyping should be considered to ensure therapeutic safety.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

The Role of Single Nucleotide Polymorphisms in Transporter Proteins and the Folate Metabolism Pathway in Delayed Methotrexate Excretion: A Case Report and Literature Review

Wang¹,

Zhao²,

Sun³

et al. 2022

PGPM

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“…[2] Hydration, alkalinization, and leucovorin rescue have evolved to routine clinical administration since Jaffe started to use HD-MTX to treat osteosarcoma in 1972,[3] but delayed excretion of methotrexate (MTX) can occur to cause gastrointestinal reactions, oral mucositis, increases in levels of liver enzymes, neurotoxicity, and hematologic toxicity. [456] These serious adverse effects can lead to treatment cessation, irreversible damage to organs, and death.…”

Section: Introductionmentioning

confidence: 99%

Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients

Zhang

Zheng

et al. 2016

Chinese Medical Journal

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Background:High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is “gold standard” therapy for osteosarcoma. Plasma concentrations of methotrexate (MTX) are closely related to its efficacy and toxicity. Delayed excretion of MTX can lead to serious adverse reactions that may result in treatment cessation, irreversible organ damage, and death. This study focused on the incidence of delayed excretion of MTX in Chinese osteosarcoma patients.Methods:A total of 1277 osteosarcoma patients were treated with HD-MTX chemotherapy (4291 cycles) from 2010 to 2015. Factors that could influence delayed excretion of MTX (gender, age, number of chemotherapy cycles, and serum concentration of MTX) were analyzed.Results:The incidence of delayed excretion of MTX (serum concentrations at 24 h [C24 h] >5 μmol/L) and severe delayed excretion of MTX (C24 h >20 μmol/L) were 6.19% and 0.86% per patient, and 2.31% and 0.26% per cycle of treatment, respectively. The incidence of severe delayed excretion of MTX was associated with gender, age, and C24 h.Conclusions:Precaution of delayed excretion of MTX is needed during osteosarcoma treatment using HD-MTX. An optimal individualized rescue strategy can be created with consideration of gender, age, and C24 h.

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Conventional chemotherapy

Sprangers¹,

Cosmai²,

Porta³

2020

Onco-Nephrology

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Two Pediatric Osteosarcoma Cases with Delayed Methotrexate Excretion: Its Clinical Course and Management

Cited by 4 publications

References 15 publications

The Role of Single Nucleotide Polymorphisms in Transporter Proteins and the Folate Metabolism Pathway in Delayed Methotrexate Excretion: A Case Report and Literature Review

The Role of Single Nucleotide Polymorphisms in Transporter Proteins and the Folate Metabolism Pathway in Delayed Methotrexate Excretion: A Case Report and Literature Review

Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients

Conventional chemotherapy

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