Preventing andmanaging toxicities of high-dose methotrexate

Scott Howard, John McCormick, Ching Hon Pui, Randal Buddington, R. Donald Harvey

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

High-dose methotrexate (HDMTX), defined as a dose higher than 500mg/m2, is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in2%–12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated.

Original languageEnglish (US)
Pages (from-to)1471-1482
Number of pages12
JournalOncologist
Volume21
Issue number12
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

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Methotrexate
Kidney
Acute Kidney Injury
Leucovorin
Urine
Mucositis
Poisons
Crystallization
Serum
Drug Interactions
Dialysis
Creatinine
Therapeutics
Morbidity
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Preventing andmanaging toxicities of high-dose methotrexate. / Howard, Scott; McCormick, John; Pui, Ching Hon; Buddington, Randal; Donald Harvey, R.

In: Oncologist, Vol. 21, No. 12, 01.12.2016, p. 1471-1482.

Research output: Contribution to journalArticle

Howard, Scott ; McCormick, John ; Pui, Ching Hon ; Buddington, Randal ; Donald Harvey, R. / Preventing andmanaging toxicities of high-dose methotrexate. In: Oncologist. 2016 ; Vol. 21, No. 12. pp. 1471-1482.
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