- Title
- A systematic review and meta-analysis of toxicity and treatment outcomes with pharmacogenetic-guided dosing compared to standard of care BSA-based fluoropyrimidine dosing
- Creator
- Glewis, Sarah; Alexander, Marliese; Khabib, Muhammad N. H.; Brennan, Annabelle; Lazarakis, Smaro; Martin, Jennifer; Tie, Jeane; Lingaratnam, Senthil; Michael, Michael
- Relation
- British Journal of Cancer Vol. 127, Issue 1, p. 126-136
- Publisher Link
- http://dx.doi.org/10.1038/s41416-022-01779-6
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2022
- Description
- Background: Serious and potentially life-threatening toxicities can occur following 5-fluorouracil/capecitabine exposure. Patients carrying Dihydropyrimidine Dehydrogenase (DPYD) variant alleles associated with decreased enzymatic function are at a greater risk of early/severe 5-fluorouracil/capecitabine toxicity. The objective of this systematic review/meta-analysis was to evaluate treatment outcomes between Pharmacogenetics Guided Dosing (PGD) versus non-PGD and within PGD (DPYD variant allele carriers versus wild type). Methods: A systematic review/meta-analysis of original publications indexed in Ovid Medline, Ovid Embase, and the Cochrane CENTRAL (Wiley) library from inception to 7-Dec-2020. Eligible studies evaluated at least one pre-defined treatment outcome measures (toxicity/hospitalisations/survival/overall response/quality of life). Results: Of 1090 identified publications, 17 met predefined eligibility criteria. The meta-analysis observed reduced incidence of grade 3/4 overall toxicity (Risk Ratio [RR] 0.32 [95% Cl 0.27–0.39], p < 0.00001) and grade 3/4 diarrhoea (RR 0.38 [95% Cl 0.24–0.61], p < 0.0001) among PGD versus non-PGD cohorts. Within PGD cohorts, there was no statistical differences for overall response rates (complete/partial) (RR 1.31 [95% Cl 0.93–1.85], p = 0.12). Similar results were found with stable disease (RR 1.27 [95% Cl 0.66–2.44], p = 0.47). Conclusion: PGD improves patient outcomes in terms of grade 3/4 toxicity, in particular overall toxicity and diarrhoea, without impacting on treatment response.
- Subject
- treatment; chemotherapy; genetics research; meta analysis
- Identifier
- http://hdl.handle.net/1959.13/1470338
- Identifier
- uon:48437
- Identifier
- ISSN:0007-0920
- Language
- eng
- Reviewed
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