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Rational administration schedule for high-dose MTX in patients with primary CNS lymphoma.
MedLine Citation:
PMID:  22530664     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstract Methotrexate (MTX) at a dose of ≥1 g/m(2) remains the most efficient treatment against primary central nervous system lymphoma (PCNSL), and is the most widely used drug in prospective clinical trials. MTX is a folate analogue that inhibits dihydrofolate reductase, thereby blocking de novo purine synthesis. MTX as well as 7-hydroxy-MTX, its main metabolite in serum, are both eliminated by the kidneys. The elimination of MTX is prolonged in patients with renal impairment, third space fluid collections and in patients receiving concurrent nonsteroidal antirheumatic drugs, benzimidazoles, sulfonamides among others. Main adverse events with high-dose MTX include severe myelosuppression, renal dysfunction and stomatitis. Supportive measures such as rigorous hydration, urine alkalinization and careful drug monitoring with supplemental leucovorin rescue are crucial to avoid significant toxicity. Strategies to optimize clinical efficacy of high-dose MTX in patients with PCNSL include administration of 3-hour instead of longer infusions, potentially supplemented with an additional intravenous MTX-bolus, and maintaining MTX dose intensity over the course of four treatment cycles. Some pharmacological studies suggest that achieving an MTX area-under-the plasma concentration-time-curve (AUC(MTX)) of between 1.000 and 1.100 μmol·h/L may improve clinical outcome, but clinical data are not conclusive at present. In this review, we analyze the impact of patient-, lymphoma-and pharmacokinetic variables on the antitumor activity of high-dose MTX in patients with PCNSL, summarize recommendations for daily clinical practice and give some suggestions for future trials.
Authors:
M Joerger; A D R Huitema; G Illerhaus; A J M Ferreri
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-25
Journal Detail:
Title:  Leukemia & lymphoma     Volume:  -     ISSN:  1029-2403     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007422     Medline TA:  Leuk Lymphoma     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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