Download PDF
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2019; 40(03): 424-426
DOI: 10.4103/ijmpo.ijmpo_157_19
Drug Review

High-dose Methotrexate

Manikandan Dhanushkodi
Department of Medical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
› Author Affiliations Financial support and sponsorship Nil.
› Further Information
   Permissions and Reprints

Abstract

High-dose methotrexate (HDMTX) is defined as methotrexate dose of ≥500 mg/m2. It is used in the treatment of acute lymphoblastic leukemia, osteosarcoma, and primary central nervous system lymphoma. Administration mandates adequate hydration; urine alkalinization; leucovorin rescue, monitoring of urine output, serum creatinine, and methotrexate levels. Delayed methotrexate clearance is managed by increasing hydration and leucovorin dose. Glucarpidase is the antidote for patients with renal toxicity. Studies from India have shown that HDMTX can be administered without monitoring of methotrexate levels with strict monitoring of urine pH, urine output, and serum creatinine and extended hydration and leucovorin doses.

Keywords

High-dose methotrexate - methotrexate levels - toxicity


Publication History

Received: 24 July 2019

Accepted: 25 July 2019

Article published online:
03 June 2021

© 2019. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. Oncologist 2016; 21: 1471-82
    CrossrefPubMedGoogle Scholar
  • 2 Treon SP, Chabner BA. Concepts in use of high-dose methotrexate therapy. Clin Chem 1996; 42: 1322-9
    CrossrefPubMedGoogle Scholar
  • 3 Nathan PC, Whitcomb T, Wolters PL, Steinberg SM, Balis FM, Brouwers P. et al. Very high-dose methotrexate (33.6 g/m (2)) as central nervous system preventive therapy for childhood acute lymphoblastic leukemia: Results of national cancer institute/Children's cancer group trials CCG-191P, CCG-134P and CCG-144P. Leuk Lymphoma 2006; 47: 2488-504
    CrossrefPubMedGoogle Scholar
  • 4 Hill FG, Richards S, Gibson B, Hann I, Lilleyman J, Kinsey S. et al. Successful treatment without cranial radiotherapy of children receiving intensified chemotherapy for acute lymphoblastic leukaemia: Results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI (ISRC TN 16757172). Br J Haematol 2004; 124: 33-46
    CrossrefPubMedGoogle Scholar
  • 5 Souhami RL, Craft AW, Van der Eijken JW, Nooij M, Spooner D, Bramwell VH. et al. Randomised trial of two regimens of chemotherapy in operable osteosarcoma: A study of the European osteosarcoma intergroup. Lancet 1997; 350: 911-7
    CrossrefPubMedGoogle Scholar
  • 6 Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P. et al. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: A report of NABTT 96-07. J Clin Oncol 2003; 21: 1044-9
    CrossrefPubMedGoogle Scholar
  • 7 Al-Quteimat OM, Al-Badaineh MA. Practical issues with high dose methotrexate therapy. Saudi Pharm J 2014; 22: 385-7
    CrossrefPubMedGoogle Scholar
  • 8 Widemann BC, Balis FM, Kim A, Boron M, Jayaprakash N, Shalabi A. et al. Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: Clinical and pharmacologic factors affecting outcome. J Clin Oncol 2010; 28: 3979-86
    CrossrefPubMedGoogle Scholar
  • 9 Cheng DH, Lu H, Liu TT, Zou XQ, Pang HM. Identification of risk factors in high-dose methotrexate-induced acute kidney injury in childhood acute lymphoblastic leukemia. Chemotherapy 2018; 63: 101-7
    CrossrefPubMedGoogle Scholar
  • 10 Park JA, Shin HY. Influence of genetic polymorphisms in the folate pathway on toxicity after high-dose methotrexate treatment in pediatric osteosarcoma. Blood Res 2016; 51: 50-7
    CrossrefPubMedGoogle Scholar
  • 11 Tiwari P, Ganesan P, Radhakrishnan V, Arivalazhan R, Ganesa TS, Dhanushkodi M. Prospective evaluation of the toxicity profile, and predictors of toxicity of high dose methotrexate in patients of acute lymphoblastic leukemia/lymphoma. Pediatr Hematol Oncol J 2018; 3: 1-5
    CrossrefGoogle Scholar
  • 12 Tiwari P, Thomas MK, Pathania S, Dhawan D, Gupta YK, Vishnubhatla S. et al. Serum creatinine versus plasma methotrexate levels to predict toxicities in children receiving high-dose methotrexate. Pediatr Hematol Oncol 2015; 32: 576-84
    CrossrefPubMedGoogle Scholar
  • 13 Vaishnavi K, Bansal D, Trehan A, Jain R, Attri SV. Improving the safety of high-dose methotrexate for children with hematologic cancers in settings without access to MTX levels using extended hydration and additional leucovorin. Pediatr Blood Cancer 2018; 65: e27241
    CrossrefPubMedGoogle Scholar
  • 14 Wall SM, Johansen MJ, Molony DA, DuBose Jr. TD, Jaffe N, Madden T. et al. Effective clearance of methotrexate using high-flux hemodialysis membranes. Am J Kidney Dis 1996; 28: 846-54
    CrossrefPubMedGoogle Scholar
  • 15 Howard SC, Pedrosa M, Lins M, Pedrosa A, Pui CH, Ribeiro RC. et al. Establishment of a pediatric oncology program and outcomes of childhood acute lymphoblastic leukemia in a resource-poor area. JAMA 2004; 291: 2471-5
    CrossrefPubMedGoogle Scholar