Estrogen decline is a risk factor for paclitaxel-induced peripheral neuropathy: Clinical evidence supported by a preclinical study.
J Pharmacol Sci
; 146(1): 49-57, 2021 May.
Article
em En
| MEDLINE
| ID: mdl-33858655
We performed clinical retrospective study in female cancer patients and fundamental experiments in mice, in order to clarify risk factors for paclitaxel-induced peripheral neuropathy (PIPN). In the clinical study, 131 of 189 female outpatients with cancer undergoing paclitaxel-based chemotherapy met inclusion criteria. Breast cancer survivors (n = 40) showed significantly higher overall PIPN (grades 1-4) incidence than non-breast cancer survivors (n = 91). Multivariate sub-analyses of breast cancer survivors showed that 57 years of age or older and endocrine therapy before paclitaxel treatment were significantly associated with severe PIPN (grades 2-4). The age limit was also significantly correlated with overall development of severe PIPN. In the preclinical study, female mice subjected to ovariectomy received repeated administration of paclitaxel, and mechanical nociceptive threshold was assessed by von Frey test. Ovariectomy aggravated PIPN in the mice, an effect prevented by repeated treatment with 17ß-estradiol. Repeated administration of thrombomodulin alfa (TMα), known to prevent chemotherapy-induced peripheral neuropathy in rats and mice, also prevented the development of PIPN in the ovariectomized mice. Collectively, breast cancer survivors, particularly with postmenopausal estrogen decline and/or undergoing endocrine therapy, are considered a PIPN-prone subpopulation, and may require non-hormonal pharmacological intervention for PIPN in which TMα may serve as a major candidate.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paclitaxel
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Doenças do Sistema Nervoso Periférico
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Estrogênios
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Antineoplásicos Fitogênicos
Tipo de estudo:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Animals
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article