Plasma 25-Hydroxyvitamin D Levels and Survival in Patients with Advanced or Metastatic Colorectal Cancer: Findings from CALGB/SWOG 80405 (Alliance) (original) (raw)
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Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer
British journal of cancer, 2009
In an earlier study, a 25-hydroxyvitamin D(3) (25(OH)D) score calculated from known predictors of vitamin D status significantly predicted plasma levels of 25(OH)D and the risk of colorectal cancer, but the influence of the 25(OH)D score on survival after diagnosis is unknown. We prospectively examined the influence of post-diagnosis predicted 25(OH)D levels on mortality among 1017 participants in the Nurses' Health Study and Health Professionals Follow-Up Study who were diagnosed with colorectal cancer from 1986 to 2004. Colorectal cancer-specific and overall mortality according to quintiles of predicted 25(OH)D levels were assessed. Cox proportional hazards models were used to calculate hazard ratios (HRs) adjusted for other risk factors of survival. Higher predicted 25(OH)D levels were associated with a significant reduction in colorectal cancer-specific (P trend=0.02) and overall mortality (P trend=0.002). Compared with levels in the lowest quintile, participants with predic...
Could vitamin D sufficiency improve the survival of colorectal cancer patients?
The Journal of Steroid Biochemistry and Molecular Biology, 2015
To determine whether a higher serum 25-hydroxyvitamin D [25(OH)D] concentration at diagnosis is associated with longer survival of colorectal cancer patients. Methods: A meta-analysis was performed of studies of the relationship between 25(OH)D and mortality of patients with colorectal cancer. A random-effects model was used to calculate a pooled hazards ratio. Homogeneity was evaluated through a DerSimonian-Laird test. Results: Higher serum concentrations of 25(OH)D were associated with lower mortality in patients with colorectal cancer. Patients in the highest quintile of 25(OH)D had 37% lower mortality from colorectal cancer compared to those in the lowest quintile of 25(OH)D (pooled odds ratio = 0.63, p < 0.0001). Doseresponse curves showed lower hazard ratios for mortality with higher serum 25(OH)D through at least 40 ng/ml. There were no exceptions. Conclusions: Higher serum 25(OH)D was associated with lower mortality of patients with colorectal cancer. These results suggest that colorectal cancer patients with deficient levels of serum 25(OH)D should have their levels restored to a normal range (30-80 ng/ml). This could be done with regular testing of serum 25(OH)D to be confident that an adequate serum level is being maintained. Additional studies would be worthwhile to evaluate confounding or the possibility of reverse causation.
JAMA, 2019
studies, higher plasma 25-hydroxyvitamin D (25[OH]D) levels have been associated with improved survival in metastatic colorectal cancer (CRC). OBJECTIVE To determine if high-dose vitamin D 3 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 D 3 (n = 69) or standard-dose vitamin D 3 (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 D 3 (median follow-up, 22.9 months), the median PFS for high-dose vitamin D 3 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 D 3 (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 D 3 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 D 3 was 16.1 ng/mL vs 18.7 ng/mL for standard-dose vitamin D 3 (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 D 3 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 D 3 , vs standard-dose vitamin D 3 , 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.
Cancer Epidemiology Biomarkers & Prevention, 2014
Circulating 25-hydroxyvitamin D (25-OHD) is associated with a reduction in risk of some cancers, but its association with prognosis among patients with cancer is poorly understood. In view of the increasing number of cancer survivors in the United States and the high prevalence of vitamin D deficiency among patients with cancer, an evaluation of the role of circulating 25-OHD in prognosis among patients with cancer is essential. We conducted a systematic review of studies published in the following databases-PubMed, OvidSP, BioMed Central, EMBASE, and Scopus till September 2013 using the following search terms: "vitamin D," "25-hydroxyvitamin D," "calcidiol," "cancer," "survival," "mortality," and "prognosis." Our search yielded 1,397 articles. From the 1,397 articles, we identified 26 studies that evaluated the associations of circulating 25-OHD with prognosis among patients with cancer. Evidence suggests that circulating 25-OHD levels may be associated with better prognosis in patients with breast and colorectal cancer, but there is a paucity of information on its association with prognosis in other cancers. This review highlights the need for further studies evaluating the role of vitamin D in prognosis among patients with cancer. Cancer Epidemiol Biomarkers Prev; 23(6); 917-33. Ó2014 AACR.
Clinical Epidemiology, 2019
Circulating 25-hydroxyvitamin D (25-OHD) levels have been inversely associated with cancer death, but the nature of this relationship is unclear. We investigated this association using repeated measurements of serum 25-OHD. Patients and methods: Pre-diagnostic serum samples were collected in population health surveys in Norway (1973-2004). Participants who subsequently developed cancer (1984-2004) provided a second serum sample at the time of cancer diagnosis. Samples were stored in the Janus Serum Bank. Repeated samples existed from 202 breast cancers, 193 lung cancers, 124 lymphomas, and 37 colon cancers. Serum 25-OHD was measured via competitive radioimmunoassay. Cox regression models assessed associations between 25-OHD and cancer-specific death (case fatality) through 2012, given as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: The median time between pre-diagnostic and diagnostic samples was 14.4 years. The median 25-OHD levels were 63.3 and 62.5 nmol/L, respectively. During follow-up, 313 cancer deaths occurred. Compared to low pre-diagnostic 25-OHD levels (<46 nmol/L), higher levels (≥46 nmol/L) had significantly lower HRs (39-54%) of case fatality. This result was also seen for the diagnostic samples. Donors who had both samples at high (≥62 nmol/L) levels had 59% lower HR of case fatality, compared to those for whom both samples were at low levels (<46 nmol/L). Furthermore, versus a decline in serum 25-OHD (median −22.4 nmol/L) from pre-diagnostic to diagnostic samples, a rise (median 22.3 nmol/L) was associated with lower case fatality (HR 0.57, 95% CI 0.43−0.75). Conclusion: Our findings suggest a causal relationship between vitamin D and cancer case fatality.
Circulating 25-hydroxyvitamin D Levels and Prognosis among Cancer Patients: A Systematic Review
Cancer Epidemiology, Biomarkers & Prevention, 2014
Circulating 25-hydroxyvitamin D (25-OHD) is associated with a reduction in risk of some cancers, but its association with prognosis among patients with cancer is poorly understood. In view of the increasing number of cancer survivors in the United States and the high prevalence of vitamin D deficiency among patients with cancer, an evaluation of the role of circulating 25-OHD in prognosis among patients with cancer is essential. We conducted a systematic review of studies published in the following databases—PubMed, OvidSP, BioMed Central, EMBASE, and Scopus till September 2013 using the following search terms: “vitamin D,” “25-hydroxyvitamin D,” “calcidiol,” “cancer,” “survival,” “mortality,” and “prognosis.” Our search yielded 1,397 articles. From the 1,397 articles, we identified 26 studies that evaluated the associations of circulating 25-OHD with prognosis among patients with cancer. Evidence suggests that circulating 25-OHD levels may be associated with better prognosis in pat...
Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer
International Journal of Colorectal Disease, 2009
Background-Preclinical and clinical evidence support an association between vitamin D deficiency and an increased risk of colorectal cancer. Normal vitamin D status has been linked to favorable health outcomes ranging from decreased risk of osteoporosis to improved cancer mortality. We performed a retrospective study to assess the impact of metastatic disease and chemotherapy treatment on vitamin D status in patients with colorectal cancer residing in Western New York.
Impact of oral vitamin D supplementation on serum 25-hydroxyvitamin D levels in oncology
Nutrition journal, 2010
Serum 25-hydroxyvitamin D [25(OH)D] is the major circulating form of vitamin D and a standard indicator of vitamin D status. Emerging evidence in the literature suggests a high prevalence of suboptimal vitamin D (as defined by serum 25(OH)D levels of <32 ng/ml) as well as an association between lower serum levels and higher mortality in cancer. We investigated the effect of oral vitamin D supplementation as a means for restoring suboptimal levels to optimal levels in cancer. This is a retrospective observational study of 2198 cancer patients who had a baseline test prior to initiation of cancer therapy at our hospital to evaluate serum 25(OH)D levels between Jan 08 and Dec 09 as part of their initial nutritional evaluation. Patients with baseline levels of < = 32 ng/ml (n = 1651) were considered to have suboptimal serum 25(OH)D levels and were supplemented with 8000 IU of Vitamin D3 (four 2000 IU D3 capsules) daily as part of their nutritional care plan. The patients were rete...
The Oncologist
Background We examined overall survival (OS) outcomes based on plasma 25-hydroxyvitamin D [25(OH)D] levels in this post hoc analysis of the phase III MPACT trial of metastatic pancreatic cancer. Materials and Methods Patients were subdivided based on 25(OH)D level: sufficient (≥30 ng/mL), relatively insufficient (20–<30 ng/mL), or insufficient (<20 ng/mL). Results Of 861 patients randomized in MPACT, 422 were included in this analysis. In the all-patients group, the median OS among those with insufficient, relatively insufficient, and sufficient 25(OH)D levels was 7.9, 9.4, and 7.8 months, respectively. No statistically significant OS difference was observed with relatively insufficient (p = .227) or sufficient (p = .740) versus insufficient 25(OH)D levels or with sufficient vs relatively insufficient (p = .301) 25(OH)D levels. Conclusion No association was observed between plasma 25(OH)D levels and survival. Further investigations are needed to understand any role of vitamin ...