Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

Systematic review (SR) of methotrexate pharmacogenomics in the treatment of paediatric cancers: Evidence and Gap (#158)

Zeyad Ibrahim 1 , Samantha Stiles 2 , Rhonda Clifford 2
  1. PCH and UWA, Shelley, WA, Australia
  2. School of Allied Health and Medical Sciences, University of Western Australia, Nedlands, WA, Australia

Methotrexate (MTX) is an antimetabolite that interferes with dihydrofolate-reductase enzyme inhibiting cell growth. Thus, MTX is used to treat various cancers and other autoimmune diseases. However, folic-acid cycle enzymes and protein-transporters exhibit extensive polymorphisms that strongly impact individual patients’ ability to handle MTX, especially at high doses. The extent of this impact is still not well measured in the literature which hinders the application of MTX genomics into practice to better treatment outcome.

 Aim:

  1. Examine the available literature to understand MTX pharmacogenomics characteristics in cancer treatment.
  2. Identify the effect of different enzymes and transporter-proteins on MTX pharmacokinetics.

 Methodology:

 A rigorous SR was conducted on the 10/8/2018 using Seven different databases; EMBASE, MEDLINE, Web Of Science, Cochrane Clinical Trial, Cochrane Systematic Reviews, Translating Research Into Practice and Google Scholar. The terms used in the search were; “P*ediatric*.mp/Adolescent*.mp/Kids/Children”, “Acute Lymphoblastic Leuk*emia*.mp/ALL/Leuk*emia*.mp/Blood Cancer”, “Osteosarcoma*.mp/Osteogenic sarcoma/Bone Cancer” and “High-Dose Methotrexate*.mp/Methotrexate*.mp/High Dose Methotrexate/HDMTX/MTX”. The SR is following the PRISMA-SR guidelines and utilising DistillerSR platform. Furthermore, an independent second reviewer was employed as well as the risk of bias “ROBIN-I” tool will be applied to the review to ensure its scientific rigors is maintained.            

Results:

A total of 6099 articles had been identified through the above databases. After deduplication using EndNote.v8x, only 5687 articles were selected for title and abstract screening (stage-I) resulted of the removal of 5305 articles as they were irrelevant/out-of-scope. Only 382 articles (stage-II) have been selected for further revision. Upon the completion of this stage, full articles screening (stage-III) followed by full articles thorough assessment and data extraction (stage-IV) will be carried via DistillerSR and adhering to PRISMA-SR guidelines.

 Conclusion:

A comprehensive and detailed SR had been conducted and awaiting the final outcome of the detailed review of the remaining articles by end of August this year.

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