ArticleBreast cancer (Tokyo, Japan)2019
Pharmacogenomic-pharmacokinetic study of selective estrogen-receptor modulators with intra-patient dose escalation in breast cancer.
Article in Breast cancer (Tokyo, Japan), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.
- Genetic Variation and Hot Flashes: A Systematic Review.The Journal of clinical endocrinology and metabolism · 2020Pooled it
- Impairment of endoxifen formation in tamoxifen-treated premenopausal breast cancer patients carrying reduced-function CYP2D6 alleles.British journal of clinical pharmacology · 2021Article
- Phase 1 study of Z-endoxifen in patients with advanced gynecologic, desmoid, and hormone receptor-positive solid tumors.Oncotarget · 2021Article
- Optimising Seniors' Metabolism of Medications and Avoiding Adverse Drug Events Using Data on How Metabolism by Their P450 Enzymes Varies with Ancestry and Drug-Drug and Drug-Drug-Gene Interactions.Journal of personalized medicine · 2020Article
- Pharmacogenomics of breast cancer: highlighting CYP2D6 and tamoxifen.Journal of cancer research and clinical oncology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 11 institutions in 2 countries.
Funding
Abstract
backgroundAn association between CYP2D6 polymorphisms and tamoxifen (TAM) efficacy has not been confirmed, partly due to unreliable prediction of active metabolite exposure solely by CYP2D6 activity. The efficacy of TAM dose escalation appears limited in poor TAM metabolizers. Since the chlorine atom on the side chain of toremifene (TOR) prevents 4-hydroxylation by CYP2D6, its contribution to active conversion of TOR is minor. We examined the role of TOR and its dose escalation among poor TAM metabolizers.
methodsThe pharmacokinetics (PK) and pharmacogenomics (PGx) of TAM and TOR were studied. Correlation between PK and CYP2D6 inhibitor use, smoking status, and PGx were examined by regression analysis. For patients showing low endoxifen levels, an intra-patient dose escalation of TOR was conducted, and TOR was increased from 40 to 120 mg for ≥ 24 weeks with PK sampling. Total activity was calculated as the sum of the concentration of each active metabolite adjusted by their respective in vitro activities.
resultsFifty and 11 of the 273 participating patients had endoxifen levels < 15 and < 7.5 ng/mL, respectively. The CYP2D6 genotype was the major determinant for TAM activity (p < 0.01). Smoking status (p = 0.07) and the CYP2C19 phenotype (p = 0.07), but not the CYP2D6 genotype (p = 0.61), showed marginally significant effects on TOR activity. TOR activity increased significantly with dose escalation, even among poor TAM metabolizers, and was maintained for ≥ 24 weeks.
conclusionTOR might be a valid alternative to TAM in patients predicted to be poor TAM metabolizers.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.