Trial reportCancer chemotherapy and pharmacology2021
Cyclophosphamide bioactivation pharmacogenetics in breast cancer patients.
Trial report in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06383338 (A Prospective Feasibility Study Investigating PhEnoconversion of CYP3A4, CYP2C19 and CYP2D6 Genotype in Paediatric and Adolescent and Young Adult patientS With an acUte diagnosiS of Hodgkin or Non-Hodgkin Lymphoma.), which is not on this map. Cited by 17 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.
A Prospective Feasibility Study Investigating PhEnoconversion of CYP3A4, CYP2C19 and CYP2D6 Genotype in Paediatric and Adolescent and Young Adult patientS With an acUte diagnosiS of Hodgkin or Non-Hodgkin Lymphoma.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Pharmacogenomic studies of fertility outcomes in pediatric cancer survivors - A systematic review.Clinical and translational science · 2024Pooled it
- Factors Influencing Phenoconversion in CYP-Mediated Drug Metabolism: A Scoping Review.Pharmacy (Basel, Switzerland) · 2026Review
- Prevalence of actionable pharmacogenomic variants in Brazilian patients with cancer.Frontiers in pharmacology · 2026Article
- Pharmacogenetics as a Future Tool to Risk-Stratify Breast Cancer Patients According to Chemotoxicity Potential from the Doxorubicin Hydrochloride and Cyclophosphamide (AC) Regimen.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Phenoconversion of CYP3A4, CYP2C19 and CYP2D6 in Pediatrics, Adolescents and Young Adults With Lymphoma: Rationale and Design of the PEGASUS Study.Clinical and translational science · 2025Article
- Protective Effects of Phycobiliproteins fromPharmaceuticals (Basel, Switzerland) · 2025Article
- Cyclophosphamide Pharmacogenomic Variation in Cancer Treatment and Its Effect on Bioactivation and Pharmacokinetics.Advances in pharmacological and pharmaceutical sciences · 2024Review
- Spray-dried cyclophosphamide-loaded polyhydroxyalkanoate microparticles: design and characterization.ADMET & DMPK · 2024Article
- NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223.Journal of Cancer · 2024Article
- In Silico Mixed Ligand/Structure-Based Design of New CDK-1/PARP-1 Dual Inhibitors as Anti-Breast Cancer Agents.International journal of molecular sciences · 2023Article
- Association between CYP2B6 genetic variability and cyclophosphamide therapy in pediatric patients with neuroblastoma.Scientific reports · 2023Article
- Royal Jelly: Beneficial Properties and Synergistic Effects with Chemotherapeutic Drugs with Particular Emphasis in Anticancer Strategies.Nutrients · 2022Review
- Lack of association of CYP2B6 pharmacogenetics with cyclophosphamide toxicity in patients with cancer.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Article
- Breast Cancer Metastasis: Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2022Review
- Effects of cyclophosphamide related genetic variants on clinical outcomes of adult hematopoietic cell transplant patients.Cancer chemotherapy and pharmacology · 2022Observational
- The Effects of Immunosuppression on the Lung Microbiome and Metabolites in Rats.Frontiers in microbiology · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeGenetic variation in the activation of the prodrug cyclophosphamide (CP) by cytochrome P450 (CYP) enzymes has been shown to influence outcomes. However, CYP are also subject to phenoconversion due to either the effects of comedications or cancer associated down-regulation of expression. The aim of this study was to assess the relationship between CP bioactivation with CYP2B6 and CYP2C19 genotype, as well as CYP2C19 phenotype, in breast cancer patients.
methodsCP and the active metabolite levels were assessed in breast cancer patients (n = 34) at cycle 1 and cycle 3 of treatment. Patients were genotyped for a series of SNP known to affect CYP2B6 and CYP2C19 function. The activity of CYP2C19 was also assessed using a probe drug.
resultsWe found a significant linear gene-dose relationship with CYP2B6 coding SNP and formation of 4-hydroxycyclophosphamide. A possible association with CYP2C19 null genotype at cycle 1 was obscured at cycle 3 due to the substantial intra-individual change in CP bioactivation on subsequent dosing.
conclusionComedications may be the cause for this inter-occasion variation in bioactivation of cyclophosphamide and the ensuing phenoconversion may account for the conflicting reports in the literature about the relationship between CYP2C19 genotype and CP bioactivation pharmacokinetics. Trial registration ANZCTR363222 (6/11/2012, retrospectively registered).
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