Polypharmacy driven synergistic toxicities in elderly breast cancer chemotherapy drug management and adverse drug reactions: a mini review
Breast cancer is increasingly diagnosed in older women (median age ≈63 years), and chemotherapy outcomes are clouded by a polypharmacy landscape—defined here as ≥5 concurrent medications—that magnifies toxicity beyond single-agent expectations. Prospective geriatric-oncology cohorts reveal a median...
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Frontiers Media S.A.
2025-08-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1654353/full |
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| author | Xiran Wang Xiran Wang Jin Yang Jin Yang Jieying Zhang Jieying Zhang Hong Yang Hong Yang |
| author_facet | Xiran Wang Xiran Wang Jin Yang Jin Yang Jieying Zhang Jieying Zhang Hong Yang Hong Yang |
| author_sort | Xiran Wang |
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| description | Breast cancer is increasingly diagnosed in older women (median age ≈63 years), and chemotherapy outcomes are clouded by a polypharmacy landscape—defined here as ≥5 concurrent medications—that magnifies toxicity beyond single-agent expectations. Prospective geriatric-oncology cohorts reveal a median of eleven concomitant drugs and clinically relevant potential drug–drug interactions (rPDDI) in up to 75% of patients; each level-1 conflict almost doubles grade 3–4 non-haematological events, while polypharmacy-frailty indices outperform chronological age for predicting unplanned hospitalisation. Age-linked gastric alkalisation, cytochrome-P450 attrition and renal decline compress pharmacokinetic space: cimetidine lifts epirubicin exposure by 39%, proton-pump inhibitors halve palbociclib troughs yet heighten neutropenia, and triazole antifungals quadruple free vincristine levels, yielding neuropathy in 87% of recipients. Beyond kinetics, overlapping end-organ liabilities—anthracycline–trastuzumab cardiotoxicity, taxane-β-blocker arrhythmia, capecitabine–warfarin haemorrhage—translate polypharmacy into a synergistic toxicity premium that erodes functional independence. Pharmacist-led reconciliation coupled with algorithmic deprescribing removes ≥1 potentially inappropriate medication in 80% of elders, while electronic rPDDI alerting and DPYD/CYP2D6 genotyping halve severe events without sacrificing efficacy. Composite scores integrating regimen complexity with genomic risk and circulating toxicity markers are emerging as real-time sentinels. By weaving mechanistic, epidemiologic and implementation evidence, this review charts how polypharmacy propels synergistic toxicities in elderly breast-cancer chemotherapy and delineates stewardship frameworks poised to reconcile oncologic potency with geriatric safety. |
| format | Article |
| id | doaj-art-0ad206cfb72b4f63bdee447314f91c0c |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-0ad206cfb72b4f63bdee447314f91c0c2025-08-26T05:27:59ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.16543531654353Polypharmacy driven synergistic toxicities in elderly breast cancer chemotherapy drug management and adverse drug reactions: a mini reviewXiran Wang0Xiran Wang1Jin Yang2Jin Yang3Jieying Zhang4Jieying Zhang5Hong Yang6Hong Yang7Peking University First Hospital Taiyuan Hospital, Taiyuan, ChinaTaiyuan Central Hospital, Taiyuan, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaFirst Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, ChinaFirst Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaPeking University First Hospital Taiyuan Hospital, Taiyuan, ChinaTaiyuan Central Hospital, Taiyuan, ChinaBreast cancer is increasingly diagnosed in older women (median age ≈63 years), and chemotherapy outcomes are clouded by a polypharmacy landscape—defined here as ≥5 concurrent medications—that magnifies toxicity beyond single-agent expectations. Prospective geriatric-oncology cohorts reveal a median of eleven concomitant drugs and clinically relevant potential drug–drug interactions (rPDDI) in up to 75% of patients; each level-1 conflict almost doubles grade 3–4 non-haematological events, while polypharmacy-frailty indices outperform chronological age for predicting unplanned hospitalisation. Age-linked gastric alkalisation, cytochrome-P450 attrition and renal decline compress pharmacokinetic space: cimetidine lifts epirubicin exposure by 39%, proton-pump inhibitors halve palbociclib troughs yet heighten neutropenia, and triazole antifungals quadruple free vincristine levels, yielding neuropathy in 87% of recipients. Beyond kinetics, overlapping end-organ liabilities—anthracycline–trastuzumab cardiotoxicity, taxane-β-blocker arrhythmia, capecitabine–warfarin haemorrhage—translate polypharmacy into a synergistic toxicity premium that erodes functional independence. Pharmacist-led reconciliation coupled with algorithmic deprescribing removes ≥1 potentially inappropriate medication in 80% of elders, while electronic rPDDI alerting and DPYD/CYP2D6 genotyping halve severe events without sacrificing efficacy. Composite scores integrating regimen complexity with genomic risk and circulating toxicity markers are emerging as real-time sentinels. By weaving mechanistic, epidemiologic and implementation evidence, this review charts how polypharmacy propels synergistic toxicities in elderly breast-cancer chemotherapy and delineates stewardship frameworks poised to reconcile oncologic potency with geriatric safety.https://www.frontiersin.org/articles/10.3389/fphar.2025.1654353/fullpolypharmacydrug–drug interactionselderly breast cancersynergistic toxicityadverse drug reactions |
| spellingShingle | Xiran Wang Xiran Wang Jin Yang Jin Yang Jieying Zhang Jieying Zhang Hong Yang Hong Yang Polypharmacy driven synergistic toxicities in elderly breast cancer chemotherapy drug management and adverse drug reactions: a mini review Frontiers in Pharmacology polypharmacy drug–drug interactions elderly breast cancer synergistic toxicity adverse drug reactions |
| title | Polypharmacy driven synergistic toxicities in elderly breast cancer chemotherapy drug management and adverse drug reactions: a mini review |
| title_full | Polypharmacy driven synergistic toxicities in elderly breast cancer chemotherapy drug management and adverse drug reactions: a mini review |
| title_fullStr | Polypharmacy driven synergistic toxicities in elderly breast cancer chemotherapy drug management and adverse drug reactions: a mini review |
| title_full_unstemmed | Polypharmacy driven synergistic toxicities in elderly breast cancer chemotherapy drug management and adverse drug reactions: a mini review |
| title_short | Polypharmacy driven synergistic toxicities in elderly breast cancer chemotherapy drug management and adverse drug reactions: a mini review |
| title_sort | polypharmacy driven synergistic toxicities in elderly breast cancer chemotherapy drug management and adverse drug reactions a mini review |
| topic | polypharmacy drug–drug interactions elderly breast cancer synergistic toxicity adverse drug reactions |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1654353/full |
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