Pharmacogenetics testing (DPYD and UGT1A1) for fluoropyrimidine and irinotecan in routine clinical care: Perspectives of medical oncologists and oncology pharmacists

Author:

Glewis Sarah12ORCID,Lingaratnam Senthil1,Krishnasamy Mei234,H Martin Jennifer5,Tie Jeanne267,Alexander Marliese12ORCID,Michael Michael26

Affiliation:

1. Department of Pharmacy, Peter MacCallum Cancer Centre, Melbourne, Australia

2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia

3. Academic Nursing Unit, Peter MacCallum Cancer Centre, Melbourne, Australia

4. VCCC Alliance, Parkville, Australia

5. School of Medicine and Public Health, University of Newcastle, New South Wales, Australia

6. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

7. Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

Abstract

Background Despite robust evidence and international guidelines, to support routine pharmacogenetic (PGx) testing, integration in practice has been limited. This study explored clinicians’ views and experiences of pre-treatment DPYD and UGT1A1 gene testing and barriers to and enablers of routine clinical implementation. Methods A study-specific 17-question survey was emailed (01 February–12 April 2022) to clinicians from the Medical Oncology Group of Australia (MOGA), the Clinical Oncology Society of Australia (COSA) and International Society of Oncology Pharmacy Practitioners (ISOPP). Data were analysed and reported using descriptive statistics. Results Responses were collected from 156 clinicians (78% medical oncologists, 22% pharmacists). Median response rate of 8% (ranged from 6% to 24%) across all organisations. Only 21% routinely test for DPYD and 1% for UGT1A1. For patients undergoing curative/palliative intent treatments, clinicians reported intent to implement genotype-guided dosing by reducing FP dose for DPYD intermediate metabolisers (79%/94%), avoiding FP for DPYD poor metabolisers (68%/90%), and reducing irinotecan dose for UGT1A1 poor metabolisers (84%, palliative setting only). Barriers to implementation included: lack of financial reimbursements (82%) and perceived lengthy test turnaround time (76%). Most Clinicians identified a dedicated program coordinator, i.e., PGx pharmacist (74%) and availability of resources for education/training (74%) as enablers to implementation. Conclusion PGx testing is not routinely practised despite robust evidence for its impact on clinical decision making in curative and palliative settings. Research data, education and implementation studies may overcome clinicians’ hesitancy to follow guidelines, especially for curative intent treatments, and may overcome other identified barriers to routine clinical implementation.

Publisher

SAGE Publications

Subject

Pharmacology (medical),Oncology

Reference28 articles.

1. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update

2. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction of DPYD and fluoropyrimidines

3. Pharmgkb [Internet]. CA, USA: Pharmgkb; [November 2018 Update, cited 13 June 2021]. Available from https://www.pharmgkb.org/guidelineAnnotation/PA166104951.

4. A systematic review and meta-analysis of toxicity and treatment outcomes with pharmacogenetic-guided dosing compared to standard of care BSA-based fluoropyrimidine dosing

5. Australian Governoment Department of Health and Aged Care Therapeutic Good Administrations [internet]. Australia: TGA; [September 2022 Update, cited 15 November 2022]. Available from https://www.tga.gov.au/news/safety-updates/fluorouracil-and-capecitabine-dpd-deficiency.

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