Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221.
J Natl Compr Canc Netw
; 21(11): 1172-1180.e3, 2023 11.
Article
en En
| MEDLINE
| ID: mdl-37935109
ABSTRACT
BACKGROUND:
Prior work suggests that patients with vitamin D insufficiency may have a higher risk of chemotherapy-induced peripheral neuropathy (CIPN) from paclitaxel. The objective of this study was to validate vitamin D insufficiency as a CIPN risk factor.METHODS:
We used data and samples from the prospective phase III SWOG S0221 (ClinicalTrials.gov identifier NCT00070564) trial that compared paclitaxel-containing chemotherapy regimens for early-stage breast cancer. We quantified pretreatment 25-hydroxy-vitamin D in banked serum samples using a liquid chromatography-tandem mass spectrometry targeted assay. We tested the association between vitamin D insufficiency (≤20 ng/mL) and grade ≥3 sensory CIPN via multiple logistic regression and then adjusted for self-reported race, age, body mass index, and paclitaxel schedule (randomization to weekly or every-2-week dosing). We also tested the direct effect of vitamin D deficiency on mechanical hypersensitivity in mice randomized to a regular or vitamin D-deficient diet.RESULTS:
Of the 1,191 female patients in the analysis, 397 (33.3%) had pretreatment vitamin D insufficiency, and 195 (16.4%) developed grade ≥3 CIPN. Patients with vitamin D insufficiency had a higher incidence of grade ≥3 CIPN than those who had sufficient vitamin D (20.7% vs 14.2%; odds ratio [OR], 1.57; 95% CI, 1.14-2.15; P=.005). The association retained significance after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; 95% CI, 1.18-2.30; P=.003) but not race (adjusted OR, 1.39; 95% CI, 0.98-1.97; P=.066). In the mouse experiments, the vitamin D-deficient diet caused mechanical hypersensitivity and sensitized mice to paclitaxel (both P<.05).CONCLUSIONS:
Pretreatment vitamin D insufficiency is the first validated potentially modifiable predictive biomarker of CIPN from paclitaxel. Prospective trials are needed to determine whether vitamin D supplementation prevents CIPN and improves treatment outcomes in patients with breast and other cancer types.Palabras clave
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Bases de datos:
MEDLINE
Asunto principal:
Deficiencia de Vitamina D
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Neoplasias de la Mama
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Enfermedades del Sistema Nervioso Periférico
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Antineoplásicos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Natl Compr Canc Netw
Asunto de la revista:
NEOPLASIAS
Año:
2023
Tipo del documento:
Article