A Pilot Study of Low and High Dose Vitamin Cholecalciferol (D3) With Pharmacokinetic and Pharmacodynamic Correlates in Patients With Resected Colon Cancer
- Compare the antiproliferative effects of 2 different doses of cholecalciferol (i.e.,
vitamin D3) in combination with calcium carbonate on the proliferative labeling index
in patients with resected colon cancer.
- Compare the effects of these doses on serum levels of 25-OH-D3, 1,25-OH-D3,
24,25-OH-D3, calcium, and parathyroid hormone in these patients.
- Determine the safety of high-dose cholecalciferol in these patients over 2 years.
- Compare the effects of these doses on several biological markers (i.e., cyclin D1,
protein kinase C, vitamin D receptor, p21, and p27) in the rectal mucosa of these
OUTLINE: This is a randomized, pilot study. Patients are randomized to 1 of 2 treatment
- Arm I: Patients receive oral low-dose cholecalciferol once daily and oral calcium
carbonate twice daily.
- Arm II: Patients receive oral high-dose cholecalciferol once daily and calcium
carbonate as in arm I.
Treatment in both arms continues for up to 2 years in the absence of disease progression or
unacceptable toxicity. All patients undergo sigmoidoscopy or colonoscopy with 4 quadrant
mucosal biopsies at baseline and after 6 months of study treatment. After their 6-month
mucosal biopsy, patients in arm I switch to high-dose cholecalciferol as in arm II.
Patients undergo blood, urine, and tissue collection periodically during study for
pharmacokinetic, pharmacodynamic, and/or histopathological analysis. Serum is collected
monthly for 3 months and then once every 3 months to assess changes in serum levels of
vitamin D and vitamin D metabolites (i.e., 1,25-OH-D3; 25-OH-D3; 24,25-OH-D3), as well as
changes in calcium and parathyroid hormone, BUN, creatinine, electrolytes, and phosphorus
levels. Urine is collected once every 3 months to assess changes in urine calcium and
creatinine levels for hypercalciuria. Tissue biopsies of normal endorectal mucosa collected
at baseline and after 6 months of study treatment are evaluated by IHC for proliferative
index, vitamin D receptor staining, p21, p27, cyclin D1, and protein kinase C.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Allocation: Randomized, Primary Purpose: Treatment
Change in proliferative labeling index of normal rectal mucosa as measured by Ki67 IHC staining
Marwan Fakih, MD
Roswell Park Cancer Institute
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|