Department of Pharmacy, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.
Br J Cancer. 2022 Jul;127(1):126-136. doi: 10.1038/s41416-022-01779-6. Epub 2022 Mar 19.
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).
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).
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).
PGD improves patient outcomes in terms of grade 3/4 toxicity, in particular overall toxicity and diarrhoea, without impacting on treatment response.
The study is registered with PROSPERO, registration number CRD42020223768.
氟尿嘧啶/卡培他滨暴露后会发生严重且可能危及生命的毒性。携带与酶功能降低相关的二氢嘧啶脱氢酶（DPYD）变异等位基因的患者发生早期/严重氟尿嘧啶/卡培他滨毒性的风险更高。本系统评价/荟萃分析的目的是评估基于药物遗传学指导剂量（PGD）与非 PGD 之间以及 PGD 内（DPYD 变异等位基因携带者与野生型）的治疗结果。
对从 Ovid Medline、Ovid Embase 和 Cochrane CENTRAL（Wiley）图书馆中收录的原始出版物进行系统评价/荟萃分析，检索时间从建库至 2020 年 12 月 7 日。符合条件的研究评估了至少一项预先定义的治疗结果测量指标（毒性/住院/生存/总体反应/生活质量）。
在 1090 篇已识别的文献中，有 17 篇符合预先设定的纳入标准。荟萃分析观察到 PGD 组与非 PGD 组相比，总体毒性（风险比 [RR] 0.32 [95% Cl 0.27-0.39]，p<0.00001）和 3/4 级腹泻（RR 0.38 [95% Cl 0.24-0.61]，p<0.0001）的发生率降低。在 PGD 队列内，总体反应率（完全/部分）（RR 1.31 [95% Cl 0.93-1.85]，p=0.12）无统计学差异。无进展疾病（RR 1.27 [95% Cl 0.66-2.44]，p=0.47）也有相似的结果。
PGD 改善了患者的治疗结果，在 3/4 级毒性方面，特别是在总体毒性和腹泻方面，而不会影响治疗反应。
该研究已在 PROSPERO 注册，注册号为 CRD42020223768。
