DPYD -Guided Dosing of Metronomic Capecitabine Plus Vinorelbine in Metastatic Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer: A Real-World Retrospective Study
Rattachement africain : es, it, jp. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
PURPOSE Metronomic chemotherapy with oral capecitabine + vinorelbine (Cape + VNL) provides synergistic cytostatic activity and antiangiogenic and immunomodulatory effects, potentially offering prolonged disease control with limited toxicity in HER2-negative metastatic breast cancer (MBC). However, efficacy in the real-world (RW) setting, especially in late lines, and the impact of dihydropyrimidine dehydrogenase ( DPYD ) polymorphisms on dose reduction and safety remain limited. METHODS In this retrospective study, 200 patients with human epidermal growth factor receptor 2 (HER2)–negative MBC were treated at the ASST Cremona Hospital (2015-2023) with metronomic Cape (1000 mg twice daily, in normal metabolizers; 500 mg twice daily, in DPYD variant carriers) + VNL (20 mg/day, once daily, 5-days-on/2-days-off). All patients underwent pretreatment DPYD genotyping and dose adjustment. Treatment was administered in the second-to-fourth setting. The primary end point was time-to-next treatment or death (TNTD); secondary end points included overall survival (OS), disease control rate (DCR) ≥24 weeks, overall response rate (ORR), safety, and genotype-toxicity correlations. RESULTS The median age was 61 years, and DPYD variants were present in 14.5% of patients; 34%, 41%, and 25% received therapy as second-, third-, and fourth-line treatment. The median TNTD was 22.0 weeks, and the OS was 64.0 weeks. The DCR was 38.5%, and the ORR was 22.0%. Efficacy was comparable between DPYD variant carriers and normal metabolizers (all P values > .05). In later lines, Eastern Cooperative Oncology Group performance status 2 and >2 metastatic sites were independent negative prognostic factors (all values P < .05). Overall, 7.5% grade 3 toxicities occurred, especially in variant carriers without dose reduction and grade 4-5 events. CONCLUSION These RW data suggest that metronomic Cape + VNL may represent a clinically active and manageable option in heavily pretreated HER2-negative MBC. Our findings support prospective evaluation of DPYD -guided dose individualization as a strategy to optimize the benefit-risk balance of fluoropyrimidine-based metronomic regimens.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- <i>DPYD</i> -Guided Dosing of Metronomic Capecitabine Plus Vinorelbine in Metastatic Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer: A Real-World Retrospective Study
- Date Crossref
- 01/08/2026
- Éditeur
- American Society of Clinical Oncology (ASCO)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Hospital Clínic de Barcelona pays non établi dans la noticeÉtablissement de santé
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Consorci Institut D'Investigacions Biomediques August Pi I Sunyer pays non établi dans la noticeStructure de recherche
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Istituti Ospitalieri di Cremona pays non établi dans la noticeÉtablissement de santé
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University of Messina Department of Human Pathology “G. Barresi” pays non établi dans la noticeUniversité ou école supérieure
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Scuola Superiore Meridionale pays non établi dans la noticeUniversité ou école supérieure
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University of Naples Federico II Department of Clinical Medicine and Surgery pays non établi dans la noticeUniversité ou école supérieure
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Università Cattolica del Sacro Cuore pays non établi dans la noticeUniversité ou école supérieure
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University of the Sacred Heart pays non établi dans la noticeUniversité ou école supérieure
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Clinic Barcelona Comprehensive Cancer Center pays non établi dans la noticeÉtablissement de santé
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August Pi I Sunyer Biomedical Research Institute (IDIBAPS) Translational Genomics and Targeted Therapies in Solid Tumors pays non établi dans la noticeStructure de recherche
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ASST of Cremona Hospital Multidisciplinary Oncology Unit and Breast Unit pays non établi dans la noticeÉtablissement de santé
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Clinical and Translational Oncology pays non établi dans la noticeÉtablissement de santé
Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer et Istituti Ospitalieri di Cremona, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.