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

Glewis, S; Alexander, M; Khabib, MNH; Brennan, A; Lazarakis, S; Martin, J; Tie, J; Lingaratnam, S; Michael, M

Author(s): Glewis, S; Alexander, M; Khabib, MNH; Brennan, A; Lazarakis, S; Martin, J; Tie, J; Lingaratnam, S; Michael, M;
Details: Publication Year 2022-07,Volume 127,Issue #1,Page 126-136
Journal Title: British Journal of Cancer
Publication Type: Review
Abstract: 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. REGISTRATION NUMBER: The study is registered with PROSPERO, registration number CRD42020223768.
Keywords: Capecitabine/adverse effects; Diarrhea/chemically induced; Dihydrouracil Dehydrogenase (NADP)/genetics; Fluorouracil/adverse effects; Humans; *Pharmacogenetics; *Quality of Life; Standard of Care; Treatment Outcome
Department(s): Pharmacy; Medical Oncology
PubMed ID: 35306539
Publisher's Version: https://doi.org/10.1038/s41416-022-01779-6
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-10-31 04:55:06

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