{"doi":"10.6004/jnccn.2023.7062","title":"Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221","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.","journal":"Journal of the National Comprehensive Cancer Network","year":2023,"id":327092,"datarank":0.8831468564486871,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":0.38331617992240646,"self_endowment_contribution":0.49983067652628066,"citer_contribution":0.38331617992240646,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":23,"citers_with_citation_signal":16,"citers_with_endowment":16,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8938,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00070564"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":504380,"name":"Gary Zirpoli","orcid":"0000-0003-1417-5349","position":1,"is_corresponding":false},{"id":299472,"name":"William E. Barlow","orcid":"0000-0003-4651-2282","position":2,"is_corresponding":false},{"id":626599,"name":"G. Thomas Budd","orcid":"0000-0002-1128-6185","position":3,"is_corresponding":false},{"id":913318,"name":"Bryan McKiver","orcid":"0000-0002-1447-5803","position":4,"is_corresponding":false},{"id":13005,"name":"Lajos Pusztai","orcid":"0000-0001-9632-6686","position":5,"is_corresponding":false},{"id":299476,"name":"Gabriel N. Hortobágyi","orcid":"0000-0002-4873-4412","position":6,"is_corresponding":false},{"id":242396,"name":"Kathy S. Albain","orcid":"0000-0002-2899-2473","position":7,"is_corresponding":false},{"id":357653,"name":"M. Imad Damaj","orcid":null,"position":8,"is_corresponding":false},{"id":34241,"name":"Andrew K. Godwin","orcid":"0000-0002-3987-9580","position":9,"is_corresponding":false},{"id":14131,"name":"Alastair M. Thompson","orcid":"0000-0003-0604-7267","position":10,"is_corresponding":false},{"id":420450,"name":"N. Lynn Henry","orcid":"0000-0002-4771-5930","position":11,"is_corresponding":false},{"id":294550,"name":"Christine B. Ambrosone","orcid":"0000-0003-1717-9943","position":12,"is_corresponding":false},{"id":321111,"name":"Kathleen A. Stringer","orcid":"0000-0003-0238-7774","position":13,"is_corresponding":false},{"id":107116,"name":"Daniel L. Hertz","orcid":"0000-0003-0501-1035","position":14,"is_corresponding":false},{"id":994586,"name":"Ciao-Sin Chen","orcid":"0000-0002-5917-0958","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T01:08:42.846627Z","pmid":"37935109","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}