Patient characteristics associated with high-risk methotrexate concentrations and toxicity.

Relling, Mary V.; Fairclough, Diane; Ayers, Dan; Crom, William R.; Rodman, John H.; Pui, Ching‐Hon; Evans, William E.

doi:10.1200/jco.1994.12.8.1667

Cited by 194 publications

(145 citation statements)

References 15 publications

Supporting

Mentioning

132

Contrasting

Order By: Relevance

“…High plasma methotrexate concentrations have been associated with increased toxicity, delayed clearance of methotrexate, and delay of subsequent courses of chemotherapy. 8,9 It is therefore important to maintain plasma concentrations within the putative cytotoxic range for leukemic blasts, but below those associated with significant toxicity. This study successfully targeted patients to concentrations within the range expected for a 5 g/m 2 dose of methotrexate, which has been associated with excellent outcome in newly diagnosed patients with ALL.…”

Section: Discussionmentioning

confidence: 99%

Individualized methotrexate dosing in children with relapsed acute lymphoblastic leukemia

et al. 2000

View full text Add to dashboard Cite

Although high-dose methotrexate has been extensively studied in children with newly diagnosed acute lymphoblastic leukemia (ALL), there are fewer data in children with relapsed ALL, many of whom have been heavily pretreated and have subclinical kidney dysfunction. We characterized the pharmacokinetics of adaptively controlled methotrexate given as a 24-h infusion during consolidation therapy in 24 children with relapsed ALL. To achieve the target steady-state concentration of 65 M, dosage adjustments were required in 14 patients, with doses ranging from 2854 to 6700 mg/m 2 per course. The mean steady-state plasma concentration (Cp ss ) of 68.0 M was different (P = 0.025) than the predicted Cp ss (mean = 87.4 M; range 35.7-184 M) had no adjustment in dose been made. The coefficient of variation in Cp ss was reduced from 41% to 18% by individualizing doses. Predisposing factors that correlated with decreased methotrexate clearance were female sex (P = 0.03), age greater than 6 years (P = 0.01), and prior history of heavy amphotericin B treatment (Ͼ30 mg/kg) (P = 0.03), but no factor predicted low clearance as well as the measured initial methotrexate clearance during the infusion (P Ͻ 0.0001). There was no life-threatening toxicity with the regimen. We conclude that dosage individualization decreases interpatient variability and avoids potentially toxic methotrexate exposures in heavily pretreated ALL patients. Leukemia (2000) 14, 221-225.

show abstract

Section: Discussionmentioning

confidence: 99%

Individualized methotrexate dosing in children with relapsed acute lymphoblastic leukemia

et al. 2000

View full text Add to dashboard Cite

show abstract

“…have been implicated [1,8]. Prior episodes probably constitute a risk, although safety of rechallenge has also been described [4][5][6]. In the above report, the paretic episode in the 2nd cycle was a grave warning-however we proceeded with the 3rd course.…”

Section: Discussionmentioning

confidence: 74%

“…The clinical features of this condition are variable ranging from transient headache and neurological deficits to life threatening paralysis and extrapyramidal symptomatology [3][4][5]. Dysphasia is well described while the ability to communicate by non-verbal means may be preserved [4].…”

Section: Discussionmentioning

confidence: 99%

“…Methotrexate induced encephalopathy occurs in 0.8-15 % of patients treated with high dose methotrexate (HDMtx) [1][2][3][4][5]. Mostly manifesting as a mild and transient neurological dysfunction, rarely it can be severe and lifethreatening [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Mostly manifesting as a mild and transient neurological dysfunction, rarely it can be severe and lifethreatening [4,5]. Similarly, majority of the patients tolerate re-challenge but it can recur with a variable reported incidence ranging from 10 to 56 % [1,2,4,6].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Methotrexate Induced Acute Encephalopathy-Occurrence on Re-challenge and Response to Aminophylline

Ganesan

Bajpai

Shah

et al. 2013

Indian J Hematol Blood Transfus

View full text Add to dashboard Cite

Methotrexate-induced acute encephalopathy is a serious complication of a common chemotherapy agent used in lymphoblastic leukemia. As this drug is considered vital for therapeutic success of leukemia therapy it is often rechallenged in these patients. A patient of acute lymphoblastic leukemia developed mild, transient hemiparesis after the 2nd dose of high dose methotrexate (5 g/m 2 ) during the consolidation phase of the BFM-95 protocol. When we repeated the drug in the 3rd cycle he developed severe life threatening quadriparesis and cranial nerve palsies. The toxicity was reversed after treatment with Aminophylline. The relevant literature is reviewed.

show abstract

Pharmacology

Sharma,

Ratain

2017

Holland‐Frei Cancer Medicine

View full text Add to dashboard Cite

Overview The biology and clinical indications relevant to systemic anticancer therapies are covered extensively in other chapters in this book. In this chapter, we will focus on the principles of clinical pharmacology as they apply to systemic anticancer therapies and will attempt to illustrate how an understanding of clinical pharmacokinetics and pharmacodynamics can optimize the therapeutic index of these agents. The United States Food and Drug Administration (FDA) conducts a question‐based clinical pharmacology and biopharmaceutics review for each approved drug ( http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/StaffPoliciesandProcedures/ucm073007.pdf ). Their reviews are publicly available on the FDA website ( http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ ) by searching for the drug name, and often include details that are not included in the product label. We will use their standard questions to introduce the principles of clinical pharmacology and will highlight examples that illustrate these principles.

show abstract

Patient characteristics associated with high-risk methotrexate concentrations and toxicity.

Abstract: This study identified several clinical variables that influence MTX disposition that, when modified, can reduce the frequency of high-risk MTX concentrations and toxicity.

Cited by 194 publications

References 15 publications

Individualized methotrexate dosing in children with relapsed acute lymphoblastic leukemia

Individualized methotrexate dosing in children with relapsed acute lymphoblastic leukemia

Methotrexate Induced Acute Encephalopathy-Occurrence on Re-challenge and Response to Aminophylline

Pharmacology

Contact Info

Product

Resources

About