Page 198 - Vitamin D and Cancer

8 Vitamin D and Cancer Chemoprevention 185

following discussion. While the doses have varied, all use the vitamin D in the form
of vitamin D (cholecalciferol)
3 .

8.3.1 Results from the Women’s Health Initiative

The Women’s Health Initiative (WHI) CaD trial was a double-blind, placebo
control factorial trial of 36,282 postmenopausal women treated with 1,000 mg/
day of calcium and 400 IU/day of vitamin D, in the form of vitamin D [35–37].
3
The primary endpoint for this trial was hip fracture with colon cancer as an estab-
lished secondary endpoint. Women were excluded from the trial if they had a
predicted survival of less than 3 years, current use of corticosteroids, a history of
renal stones, and regular intake of vitamin D supplements of 600 IU/day.
Adherence between the treatment groups was comparable as was the frequency
of sigmoidoscopy.
Colorectal Cancer (CRC) Endpoint: After an average of 7 years of follow-up,
168 were diagnosed with colon cancer in the treatment group and 154 were diag-
nosed in the placebo group. These results showed a non-significant difference in the
rates of colorectal cancer, with a hazard ratio (HR) of 1.08 (95% confidence inter-
val (CI) 0.86–1.34). The association between the treatments and colorectal cancer
did not change when women with prior CRC were excluded.
Breast Cancer (BC) Endpoint: The hazard ratio (HR) for invasive breast cancer
was 0.96 (95% CI = 0.85–1.09) between the treatment group (n = 528) and the
placebo group (n = 546), after an average of 7 years of follow-up. No significant
interactions were noted with physical activity or BMI, both independent risk
factors for breast cancer. Breast cancer histology and stage were not significant
factors in breast cancer rates between the two treatment groups, however the
tumors found in the treated patients were significantly smaller, with a p = .05.
Mortality endpoint: another secondary endpoint evaluated in the WHI Calcium-
Vitamin D trial was total mortality. A total of 744 deaths were reported in the
treatment group versus 807 in the placebo group. The HR for total mortality was
0.91 (95% CI = 0.83–1.01). Additional HRs calculated for stroke and cancer were
consistently non-significant. Age and seasonality did not show significant interac-
tions with the mortality outcome.
Toxicity and Safety of the Interventions: As reported in 2006, there was no
significant association with the treatment groups and death (HR = 0.91, 95%
CI = 0.83–1.01), total cancer risk (HR = 0.98, 95% CI = 0.91–1.05), cancer death or
colorectal polyps (HR = 0.94, 95% CI = 0.83–1.01). The major toxicity of vitamin
D supplementation is related to increased serum calcium and renal stones. There
was a significant increase in the reports of kidney stones in women in the treatment
versus placebo groups (HR = 1.17, 95% CI = 1.02–1.34, p = .02). While there were
no obvious benefits of supplementation with calcium and vitamin D , there was an
3
increase in reported toxicities, even at a dose that is now considered low by current
supplementation levels.