Vitamin D Supplementation in Breast Cancer Patients

This study is a two-arm randomized controlled trial with 132 participants, evenly randomized into an intervention group and a control group. Both groups are scheduled to receive Adriamycin-Cyclophosphamide followed by paclitaxel (AC-T) chemotherapy protocol. The intervention group will undergo paclitaxel-based chemotherapy, along with vitamin D replacement therapy. Conversely, the control group will follow the AC-T protocol without the addition of vitamin D replacement therapy.

Inclusion criteria

• Female aged 18 to 65 years old.
• Histologically confirmed breast cancer.
• Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2 [21] [22].
• All patients should fulfill the criteria of the initiation of taxane-based chemotherapy such as absolute neutrophil count (ANC) > 1,500/mcL, platelets > 100,000/mcL, hemoglobin ≥ 9 g/mL, Aspartate Aminotransferase (AST) (Serum Glutamic-Oxaloacetic Transaminase) (SGOT) to Alanine Aminotransferase (ALT), (Serum Glutamic-Pyruvic Transaminase) (SGPY) ratio (AST (SGOT)/ALT (SGPT)) < 2.5 x institutional upper limit of normal (ULN), total bilirubin less than or equal to 1.5 x institutional ULN, serum creatinine < 1.5 x institutional ULN.
• Stage I-III breast cancer scheduled to undergo adjuvant or neoadjuvant paclitaxel-based chemotherapy for breast cancer using doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² followed by paclitaxel 80 mg/m² weekly for 12 weeks protocol code BRAJACTW [23].
• Vitamin D insufficiency defined as serum level < 30 ng/ml.
• Ability to give informed consent as per the legal requirement.

Exclusion criteria

• Prior neurotoxic chemotherapy including paclitaxel.
• Metastatic carcinoma.
• History of any other malignancy except malignancy that was treated with curative intent and for which there has been no known active disease for more than 3 years prior to randomization, curatively treated non-melanoma skin malignancy, cervical cancer in situ, in situ ductal carcinoma, or breast in situ lobular carcinoma.
• Grade II neuropathy or higher based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. neurosensory or neuromotor neuropathy, regardless of causality.
• Patients who are scheduled to receive any neurotoxic chemotherapeutic agents such as platinum compounds (carboplatin, cisplatin), vinorelbine, eribulin, and ixabepilone.
• Diabetes mellitus
• Psychiatric disorders that limit ability to comply with study protocol i.e., history of regular exacerbation of major psychosis (schizophrenia, bipolar disorder) in last 2 years.
• Known Fibromyalgia
• Gastric bypass surgery.
• Patients with chronic granuloma forming disorders (sarcoidosis or tuberculosis TB).
• Known hyperparathyroidism.
• Known thyroid dysfunction.
• Known positive test for human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.
• Pregnancy and lactation.
• Hypercalcemia (corrected blood calcium > 10.5 mg/dl or > 2.6 mmol/L)[24]
• Hyperphosphatemia, serum phosphate concentration > 4.5 mg/dL [25]
• History of symptomatic genitourinary stones within the past year.
• Allergy to any cholecalciferol dosage form component.
• Alcohol consumption.
• Regular use of vitamin D > 2000 IU daily over the past year.
• Inability to swallow pills.
• Medications that may interfere with vitamin D metabolism, including enzyme inducing anticonvulsants, lithium, phenytoin, verapamil, orlistat, tuberculosis medications as isoniazid, and/or rifampin and estrogen-containing medications.
• Patients receiving any of the following medications used to prevent CIPN: vitamin E, glutamine, nortriptyline, amitriptyline, tricyclic antidepressants, pregabalin, and duloxetine and other nutritional supplements as vitamin B during taxane administration.