{"entity":{"id":"paper-ng-jama","kind":"paper","name":"Effect of High-Dose vs Standard-Dose Vitamin D3 Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer: The SUNSHINE Randomized Clinical Trial","aka":[],"tldr":"Paper cited by one technology page, indexed on Europe PMC as PubMed record 30964527 and published in JAMA; the citing page links this DOI, which is how the record was matched.","summary":"Importance: In observational studies, higher plasma 25-hydroxyvitamin D (25[OH]D) levels have been associated with improved survival in metastatic colorectal cancer (CRC).\n\nObjective: To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with metastatic CRC.\n\nDesign, setting, and participants: Double-blind phase 2 randomized clinical trial of 139 patients with advanced or metastatic CRC conducted at 11 US academic and community cancer centers from March 2012 through November 2016 (database lock: September 2018).\n\nInterventions: mFOLFOX6 plus bevacizumab chemotherapy every 2 weeks and either high-dose vitamin D3 (n = 69) or standard-dose vitamin D3 (n = 70) daily until disease progression, intolerable toxicity, or withdrawal of consent.\n\nMain outcomes and measures: The primary end point was progression-free survival (PFS) assessed by the log-rank test and a supportive Cox proportional hazards model. Testing was 1-sided. Secondary end points included tumor objective response rate (ORR), overall survival (OS), and change in plasma 25(OH)D level.\n\nResults: Among 139 patients (mean age, 56 years; 60 [43%] women) who completed or discontinued chemotherapy and vitamin D3 (median follow-up, 22.9 months), the median PFS for high-dose vitamin D3 was 13.0 months (95% CI, 10.1 to 14.7; 49 PFS events) vs 11.0 months (95% CI, 9.5 to 14.0; 62 PFS events) for standard-dose vitamin D3 (log-rank P =.07); multivariable hazard ratio for PFS or death was 0.64 (1-sided 95% CI, 0 to 0.90; P =.02). There were no significant differences between high-dose and standard-dose vitamin D3 for tumor ORR (58% vs 63%, respectively; difference, -5% [95% CI, -20% to 100%], P =.27) or OS (median, 24.3 months vs 24.3 months; log-rank P =.43). The median 25(OH)D level at baseline for high-dose vitamin D3 was 16.1 ng/mL vs 18.7 ng/mL for standard-dose vitamin D3 (difference, -2.6 ng/mL [95% CI, -6.6 to 1.4], P =.30); at first restaging, 32.0 ng/mL vs 18.7 ng/mL (difference, 12.8 ng/mL [95% CI, 9.0 to 16.6], P <.001); at second restaging, 35.2 ng/mL vs 18.5 ng/mL (difference, 16.7 ng/mL [95% CI, 10.9 to 22.5], P <.001); and at treatment discontinuation, 34.8 ng/mL vs 18.7 ng/mL (difference, 16.2 ng/mL [95% CI, 9.9 to 22.4], P <.001). The most common grade 3 and higher adverse events for chemotherapy plus high-dose vs standard-dose vitamin D3 were neutropenia (n = 24 [35%] vs n = 21 [31%], respectively) and hypertension (n = 9 [13%] vs n = 11 [16%]).\n\nConclusions and relevance: Among patients with metastatic CRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy resulted in a difference in median PFS that was not statistically significant, but with a significantly improved supportive hazard ratio. These findings warrant further evaluation in a larger multicenter randomized clinical trial.\n\nTrial registration: ClinicalTrials.gov Identifier: NCT01516216.\n\nIndexed on Europe PMC as PubMed record 30964527 (DOI 10.1001/jama.2019.2402). Matched by DOI alone: one technology page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"JAMA 2019","url":"https://doi.org/10.1001/jama.2019.2402"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30964527/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30964527"}],"tags":["europepmc-ingest"],"related":["vitamin-d-omega3-supplementation"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jama"],"dependsOn":[],"notes":[],"journal":"JAMA","year":2019,"doi":"10.1001/jama.2019.2402","pmid":"30964527","authors":"Ng K, Nimeiri HS, McCleary NJ, et al.","paperType":"rct","findings":[],"whatItMeans":"One technology page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-ng-jama/","neighbours":{"technology":[{"id":"vitamin-d-omega3-supplementation","kind":"technology","name":"Vitamin D and omega-3 supplementation","route":"/technologies/vitamin-d-omega3-supplementation/"}],"journal":[{"id":"jama","kind":"journal","name":"JAMA","route":"/journals/jama/"}]}}