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

Zhang, Wei; Zhang, Qing; Zheng, Tingting; Jian-cun, Zhen; Niu, Xiaohui

doi:10.4103/0366-6999.192781

Cited by 16 publications

(13 citation statements)

References 12 publications

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“…Several adverse nervous system reactions have also been associated with HD-MTX chemotherapy. At present, the use of HD-MTX chemotherapy remains limited due to the risk of potentially fatal MTX poisoning or bone marrow suppression (35,36). A number of scholars have reported that patients exhibited adverse reactions of differing types and degrees following the use of the MTX-MTX-DDP/ADM regimen (37).…”

Section: Problems With Chemotherapymentioning

confidence: 99%

Progress in the chemotherapeutic treatment of osteosarcoma (Review)

et al. 2018

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Osteosarcoma (OS) is the most common type of primary bone tumor in children and adolescents and has been associated with a high degree of malignancy, early metastasis, rapid progression and poor prognosis. However, the use of adjuvant chemotherapy improves the prognosis of patients with OS. OS chemotherapy is based primarily on the use of adriamycin, cisplatin (DDP), methotrexate (MTX), ifosfamide (IFO), epirubicin (EPI) and other drugs. Previous studies have revealed that the survival rate for patients with OS appears to have plateaued: 5-year survival rates remain close to 60%, even with the use of combined chemotherapy. The most limiting factors include complications and fatal toxicity associated with chemotherapy agents, particularly high-dose MTX (HD-MTX), for which high toxicity and great individual variation in responses have been observed. Docetaxel (TXT) is a representative member of the relatively recently developed taxane class of drugs, which function to inhibit OS cell proliferation and induce apoptosis. Recently, more clinical studies have reported that TXT combined with gemcitabine (GEM) is effective in the treatment of OS (relapse/refractory and progressive), providing evidence in support of potential novel treatment strategies for this patient population. However, there is still no global consensus on this type of chemotherapy approach. The present review summarizes current studies surrounding progress in the chemotherapeutic treatment of OS and discusses the advantages and potential feasibility of TXT+GEM in the treatment of OS.

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Section: Problems With Chemotherapymentioning

confidence: 99%

Progress in the chemotherapeutic treatment of osteosarcoma (Review)

et al. 2018

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“…Several studies in children and young adults or adults with osteosarcoma have reported that the elimination of MTX is not affected by gender (9,17,23). On the other hand, in a study including children and adults, Zhang et al reported that among patients with DEM, which was defined as a concentration of MTX at 24 h of >5 μM, no significant difference was observed between males and females, but the incidence of severe DEM, which was defined as a concentration of MTX at 24 h of >20 μM, was significantly higher in female patients than in male patients (24). In our study, DEM was defined as a blood concentration of MTX at 24 h of >42.2 μM.…”

Section: Discussionmentioning

confidence: 97%

Risk Factors for Delayed Elimination of Methotrexate in Children, Adolescents and Young Adults With Osteosarcoma

Misaka¹,

Suga²,

Staub³

et al. 2020

In Vivo

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Background/Aim: High-dose methotrexate (HD-MTX) is pivotal chemotherapy in the treatment of patients with osteosarcoma. Blood concentrations of MTX are associated with several side effects, but there are large individual differences in the elimination of MTX. The aim of this study was to explore risk factors for delayed elimination of MTX in children, adolescents and young adults with osteosarcoma. Patients and Methods: We conducted a retrospective study on Japanese patients with osteosarcoma who were treated with HD-MTX at Kanazawa University Hospital from April 2006 to March 2015. Risk factors for delayed elimination of methotrexate were identified by multiple logistic regression analysis. Results: A total of 92 cycles of HD-MTX therapy were analyzed. Female and lower creatinine clearance (CCr) were identified as independent risk factors for delayed elimination of MTX. Conclusion: Knowing the factors associated with delayed elimination of MTX could lead to safer and optimized chemotherapy for patients with osteosarcoma.

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“…Previous studies found that being female was an independent risk factor for the development of LP after MTX treatment for OS [ 14 ]. Currently, there are few studies on the effect of sex on MTX metabolism, and the results are controversial.…”

Section: Discussionmentioning

confidence: 99%

Nomogram predicting leukopenia in osteosarcoma after high-dose methotrexate chemotherapy

et al. 2022

Aging

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Purpose: To explore the trends of plasma drug concentration changes after high-dose methotrexate (MTX) treatment of osteosarcoma (OS), analyse the risk factors for leukopenia (LP) after MTX treatment, and establish a LP prediction nomogram. Methods: A total of 35 OS patients at Tianjin Medical University Cancer Institute and Hospital between 2017 and 2021 were collected (the construction cohort). Another 12 OS patients between 2019 and 2021 in P.A. Hertsen Moscow Oncology Research Center were involved (the external validation cohort). Peripheral venous blood MTX concentration (C MTX ) was monitored at 0h, 6h, 24h, 48h and 72h after MTX administration. The characteristics were collected: age, sex, body surface area, lesion site, pathological subtype, pathological fractures, American Joint Committee on Cancer (AJCC) clinical stage, MTX dose, tumour necrosis, Ki-67 index, erythrocyte count, haemoglobin count, white blood cell count, platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, albumin concentration, creatinine, alkaline phosphatase, and lactate dehydrogenase. Logistic regression analysis was used to determine the risk factors for LP occurrence. Significant factors were used to construct the prediction nomogram. Results: A total of 128 MTX chemotherapy cycles from 35 OS patients were included. Female, Ki-67>20%, C MTX >112μmol/L at 6h, PLT, and AST were risk factors for post-chemotherapy LP occurrence. The LP prediction nomogram was created and validated. Conclusions: Female, C MTX at 6h, Ki-67 index, AST and PLT before MTX treatment were risk factors for LP in OS patients who received MTX treatment. The established nomogram can guide personalized LP prediction in OS patients receiving MTX chemotherapy.

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

Cited by 16 publications

References 12 publications

Progress in the chemotherapeutic treatment of osteosarcoma (Review)

Progress in the chemotherapeutic treatment of osteosarcoma (Review)

Risk Factors for Delayed Elimination of Methotrexate in Children, Adolescents and Young Adults With Osteosarcoma

Nomogram predicting leukopenia in osteosarcoma after high-dose methotrexate chemotherapy

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