Evidence map›Paper›PMID 35606478›Full record

ArticleSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer2022

Lack of association of CYP2B6 pharmacogenetics with cyclophosphamide toxicity in patients with cancer.

Mary Hwang, Sarah Medley, Faisal Shakeel, Brett Vanderwerff, Matthew Zawistowski, Kelley M Kidwell, Daniel L Hertz

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Article in Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 5 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Mary HwangDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, Room 2560C, 428 Church St., Ann Arbor, MI, 48109-1065, USA.
Sarah MedleyDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109-2029, USA.
Faisal ShakeelDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, Room 2560C, 428 Church St., Ann Arbor, MI, 48109-1065, USA.
Brett VanderwerffDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109-2029, USA.
Matthew ZawistowskiDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 48109-2029, USA.
Kelley M KidwellDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, 48109-2029, USA.
Daniel L HertzDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, Room 2560C, 428 Church St., Ann Arbor, MI, 48109-1065, USA. DLHertz@med.umich.edu.ORCID http://orcid.org/0000-0003-0501-1035
University of Michigan · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeCyclophosphamide is a commonly used cancer agent that is metabolically activated by polymorphic enzymes. This study aims to investigate the association between predicted activity of candidate pharmacogenes with severe toxicity during cyclophosphamide treatment.

methodsGenome-wide genetic data was collected from an institutional genetic data repository for CYP2B6, CYP3A4, CYP2C9, CYP2C19, GSTA1, GSTP1, ALDH1A1, ALDH3A1, ABCC1, ABCB1, and ERCC1. Treatment and toxicity data were retrospectively collected from the patient's medical record. The a priori selected primary hypothesis was that patients who have CYP2B6 reduced metabolizer activity (poor or intermediate (PM/IM) vs. normal (NM) metabolizer) have lower risk of severe toxicity or cyclophosphamide treatment modification due to toxicity.

resultsIn the primary analysis of 510 cyclophosphamide-treated patients with available genetic data, there was no difference in the odds of severe toxicity or treatment modification due to toxicity in CYP2B6 PM/IM vs. NM (odds ratio = 0.97, 95% Confidence Interval: 0.62-1.50, p = 0.88). In an exploratory, statistically uncorrected secondary analysis, carriers of the ALDH1A1 rs8187996 variant had a lower risk of the primary toxicity endpoint compared with wild-type homozygous patients (odds ratio = 0.31, 95% Confidence Interval: 0.09-0.78, p = 0.028). None of the other tested phenotypes or genotypes was associated with the primary or secondary endpoints in unadjusted analysis (all p > 0.05).

conclusionThe finding that patients who carry ALDH1A1 rs8187996 may have a lower risk of cyclophosphamide toxicity than wild-type patients contradicts a prior finding for this variant and should be viewed with skepticism. We found weak evidence that any of these candidate pharmacogenetic predictors of cyclophosphamide toxicity may be useful to personalize cyclophosphamide dosing to optimize therapeutic outcomes in patients with cancer.

Indexed as

Aldehyde Dehydrogenase 1 FamilyCytochrome P-450 CYP2B6NeoplasmsPharmacogeneticsRetinal DehydrogenaseCyclophosphamideGenotypeHumansRetrospective StudiesAldehyde Dehydrogenase 1 FamilyALDH1A1 protein, humanCyclophosphamideCYP2B6 protein, humanCytochrome P-450 CYP2B6Retinal DehydrogenaseALDH1A1CyclophosphamideCYP2B6PharmacogeneticToxicityTreatment discontinuation

Identifiers

PMID35606478
OpenAlexW4281401095

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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.