Randomized phase III trial to determine the effectiveness of High dose versus Standard dose of Vitamin D2 (Ergocalciferol) given with Docetaxel in patients with metastatic breast cancer

2 Arms Randomization in patients with metastatic breast cancer.

Arm A = Docetaxel + High dose Vitamin D2

Arm B = Docetaxel + Standard dose Vitamin D2

Inclusion Criteria:

• Histologically proven metastatic adenocarcinoma of the breast.
• Gender: female.
• Age ≥18 years.
• ECOG performance status ≤ 2.(see appendix I)
• 25 (OH) Vitamin D level ≤ 100nmol/L (40ng/L).
• No more than 1 prior chemotherapy regimen not including Docetaxel or Paclitaxel for metastatic breast cancer.
• Patients progressed on Doxorubicin or epirubicin as first line for metastatic breast cancer is eligible.
• Concurrent bisphosphonate therapy allowed.
• Life expectancy more than 6 months
• At least 12 months since prior adjuvant or neo-adjuvant chemotherapy including Taxanes regimens.
• Adequate hematologic, hepatic and renal function.
• Written informed consent.

Exclusion Criteria:

• Pregnant or lactating women.

• Male breast cancer.

• Women of childbearing potential unless surgically sterile or using adequate measures of contraception.

• Metastatic inflammatory breast cancer.

• CNS metastasis.

• Leptomeningeal carcinomatosis.

• Malignant hypercalcemia.

• History of kidney stones.

• History of active primary hyperparathyroidism.

• Normal 25 (OH) Vitamin D level ≥100 nmol/L or ≥ 40 ng/L.

• Previous or concomitant malignancy of any type, except adequately treated basal cell carcinoma of the skin or in situ cervix cancer.

• Patient on any anti-Psychotic medications or Steroid therapy.

• History of malabsorption syndrome (pancreatic insufficiency, celiac disease and tropical sprue).

• Any of the following abnormal baseline hematological values:

  • ANC < 1.0 x109/L, or platelets < 100.000 x 109/L.

• Any of the following abnormal laboratory tests: total serum bilirubin >2.00 x ULN (upper limit of normal), AST, ALT > 2.5 x ULN or ALP >2.50 x ULN (upper limit of normal).