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
JAMA. 2019;321(14):1370-1379. doi:10.1001/jama.2019.2402
Would have had far more benefit if they had done one or more of the following
- Started with a Vitamin D loading dose (e.g. 400,000 IU over a week)
- Had used a dose size of at least 4,000 IU of vitamin D
- Had used less frequent than daily dosing
- Had supplemented to increase the activation of the vitamin D Receptor - such as Resveratrol
Note: Even better if had high vitamin D years before, as Vitamin D PREVENTS colon cancer
Colon Cancer
- Colorectal cancer is associated with Vitamin D (17 meta-analyses so far) – July 2018
- Death from Colon Cancer 8 X less likely if good level of vitamin D – Nov 2018
- Cancer - Colon category listing has
134 items along with related searches - Note: 2,000 IU does not result in a "good level"
- Overview Cancer-Colon and vitamin D has the following Colon Cancer Prevention charts
- Chemotheraphy not work as well with low Vitamin D (colon cancer this time) – Aug 2018
- Note: 4,000 IU daily dosing would NOT have helped Chemotherapy - would have taken months to increase the vitamin D levels
Vitamin D Receptor and Cancers
Items in both categories Vitamin D Receptor and Cancer - Colon:
- Colon Cancer protects itself by changing the VDR and CYP3A4 genes – Dec 2022
- 14th activator of the Vitamin D Receptor – Butyrate (from gut bacteria, or supplement)
- Colon cancer risk increases 30X if you have the worst vitamin D receptor mutation – Jan 2021
- Book: Sunlight, UV, Vitamin D and Receptor, Skin and other Cancers - Dec 2020
- Colorectal Cancer Patients 2.4 X more likely to have poor Vitamin D receptors (less D to cells) – April 2020
- Colorectal cancer linked to poor Vitamin D Receptor (yet again) – Jan 2020
- Colorectal Cancer risk increases when genes reduce the vitamin D levels – Aug 2019
- Risks of Colorectal Cancer, IBD, etc slightly increased if poor Vitamin D Receptor – Aug 2018
- Cancer and the Vitamin D Receptor, a primer – Sept 2017
- Advanced Colon Cancer risk is doubled or halved with 1000 IU of Vitamin D, depends on Vitamin D Receptors – RCT May 2017
- Colon Cancer survival 3.1 X less likely if poor Vitamin D Receptor – Aug 2017
- Risk of Cancer increased if poor Vitamin D Receptor – meta-analysis of 73 studies Jan 2016
- 10 percent of colon cancer linked to Vitamin D Receptor – meta-analysis April 2012
Items in both categories Vitamin D Receptor and Cancer
- Cancers are associated with low vitamin D, poor vaccination response and perhaps poor VDR – July 2022
- Poor prognosis of solid childhood cancers 14.7 X more likely with a poor Vitamin D Receptor – July 2022
- Cancers and Vitamin D Receptors, including change with race – Feb 2021
- Needing a high level of vitamin D is a good clue that the Vitamin D Receptor is deactivated
- Vitamin D Receptor and Cancer
- Book: Sunlight, UV, Vitamin D and Receptor, Skin and other Cancers - Dec 2020
- How cancer is fought by Vitamin D (Ovarian this time) – Feb 2020
- 8 ways that Cancer might be prevented by Vitamin D - June 2019
- Cancer is leading cause of death - Vitamin D and Receptor activators help
- The Role of Resveratrol in Cancer Therapy – Dec 2017
- A poor Vitamin D Receptor is associated with many cancers (oral cancer in this case) – Jan 2019
- Overview of Vitamin D Actions in Cancer – 31 page chapter in a book – 2018
- Cancer treatment by Vitamin D sometimes is restricted by genes – Oct 2018
- Vitamin D receptor is essential for both normal and cancerous cells in the lab – June 2018
- Active Vitamin D reduces Ovarian Cancer stem cells growth by 4X (via Vitamin D receptor in lab rat) – March 2018
- Cancer and the Vitamin D Receptor, a primer – Sept 2017
- Cancer risks and Vitamin D Receptors – association is unclear – 2017
- Vitamin D, Vitamin D Receptor and Cancer – Nov 2016
- Risk of Cancer increased if poor Vitamin D Receptor – meta-analysis of 73 studies Jan 2016
- Role of Vitamin D in human Diseases and Disorders – An Overview – DBP, VDR June 2014
- Vitamin D Receptor role in Autoimmune Diseases and or cancers – Nov 2013
- Vitamin D receptor polymorphisms are risk factors for various cancers – meta-analysis Jan 2014
 Download the PDF from VitaminDWiki
Fewer adverse effects if get Vitamin D
Key Points
- Question Does high-dose vitamin D3 supplementation prolong progression-free survival when added to standard chemotherapy in patients with advanced or metastatic colorectal cancer?
- Findings In this phase 2 randomized clinical trial that included 139 patients with advanced or metastatic colorectal cancer, treatment with chemotherapy plus high-dose vitamin D3 supplementation vs chemotherapy plus standard-dose vitamin D3 resulted in a median progression-free survival of 13 months vs 11 months, respectively, that was not statistically significant, but a multivariable hazard ratio of 0.64 for progression-free survival or death that was statistically significant.
- Meaning These findings regarding a potential role for high-dose vitamin D3 supplementation in the treatment of patients with advanced or metastatic colorectal cancer warrant further evaluation in a larger multicenter randomized clinical trial.
Importance In observational studies, higher plasma 25-hydroxyvitamin D (25OHD) levels have been associated with improved survival in metastatic colorectal cancer (CRC).
Objective To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with metastatic CRC.
Design, 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).
Interventions 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.
Main 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.
Results 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%]).
Conclusions 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.
Advanced Colorectal Cancer survival is increased somewhat with 4,000 IU of vitamin D – RCT April 20193278 visitors, last modified 10 Apr, 2019, This page is in the following categories (# of items in each category)Attached files
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