It appears that the story on vitamin E and its role in human health remains incomplete. It is apparent that vitamin E supplementation involves many variables, some of which include its uptake from the intestine, the preference for α-tocopherol, transport by tocopherol specific proteins and lipid transporters and the differential metabolism of different vitamin E isoforms. The fundamental differences within population genetics can have significant implications for the effect that dietary supplementation might have on human health. When evaluating the efficacy of vitamin E prophylactic or therapeutic use in previous and future studies, it is critical to consider dosage to be administered, form of vitamin E and source (such as whether from synthetic or purified from natural sources). Further studies are needed to determine the effects of all vitamin E isoforms on cell growth, tumorigenicity, to clarify its possible use as an adjuvant to existing chemotherapeutics. The Alpha-Tocopherol, Beta Carotene (ATBC) Cancer Prevention Study Group and Selenium and Vitamin E Cancer Prevention Trial (SELECT) studies along with the numerous studies of vitamin E should help guide the next chapter of vitamin E research.
A Phase I Dose-Escalation Study Evaluating the Pharmacokinetics, Safety and Tolerability of Oral Gamma-Delta-Tocotrienol (GDT) in Patients with Castration-Resistant Prostate Cancer (CRPC)
Prof Azad Hassan A. Razack, University of Malaya Medical Centre, Malaysia
Objective: In this study, we intend to determine Gamma-Delta Tocotrienol’s (GDT) safety and tolerability in patients with castrate-resistant prostate cancer (CRPC). In addition, GDT’s pharmacokinetic profile in this cohort of patients will be investigated.
Study Type: Interventional
Study Design: Dose-escalation, pharmacokinetics study
Subjects: Castrate-resistant prostate cancer patients
Intervention: Gamma-Delta Tocotrienol (GDT; Davos Life Science Pte Ltd)
- Safety and tolerability
- GDT isomer plasma concentration [ time frame: 0, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours ]
Secondary Outcome: Circulating tumor cell (CTC) levels and inflammatory biomarkers (IL-8, MCP-1, MIP-1 alpha, IFN-gamma, IL-1B, IL-4, IL-6, IL-10, IL-12 (p70), IL-17A, Il-23, IL-27, TNF-alpha, MIP-3 alpha, CRP) [time frame: baseline and day 22]
Methodology: During pharmacokinetic evaluation wherein GDT will be taken as a single dose, participants will receive oral GDT for 21 days at 400, 800, 1600, 2400 and 3200 mg/day for 21 days. Pharmakokinetic and safety profiles will be evaluated on the 8th, 15th and 22nd day.
A Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Vitamin E δ-Tocotrienol Administered to Subjects With Resectable Pancreatic Exocrine Neoplasia
Gregory Springett, M.D., Ph.D.H., Moffitt Cancer Center (USA)
Objective: The purpose of this study is to determine the safest dose of the study drug Vitamin E delta-tocotrienol, how often it should be taken, and how well people with pancreatic tumors tolerate Vitamin E delta-tocotrienol.
Study Type: Interventional
Study Design: Open Label, Safety Efficacy Study
Subjects: Patients with resectable pancreatic neoplasia
Intervention: Vitamin E delta-tocotrienol
Primary Outcome: To determine the recommended Phase II dose of Vitamin E δ-Tocotrienol which will be defined as the biologic effective dose (BED) which induces significant apoptosis in the pancreatic neoplastic cells of resected tumor specimens following oral administration of Vitamin E δ-Tocotrienol twice daily for 14 (± 2)days prior to surgery, and one dose the day of surgery.
Secondary Outcome: To characterize the safety and tolerability of Vitamin E δ-Tocotrienol when orally administered at up to 5.6 times the predicted biological effective dose (1600mg twice daily) for 14 (± 2) consecutive days and one dose the day of surgery in patients with pancreatic neoplasia.
Methodology: This study consists of the following: (1) A Pre-Treatment Period in which participants are consented and qualified for the study; (2) A Study Treatment Period in which participant will receive Vitamin E δ-Tocotrienol administered orally twice daily for 14 (±2) consecutive days and once on the day of surgery, with associated pharmacokinetic and pharmacodynamic sampling; (3) A Post Treatment Period in which laboratory and physical examinations are performed. Adverse events will be recorded throughout the study.
Effectiveness of Tocotrienol-rich Fraction Combined With Tamoxifen in the Management of Women With Early Breast Cancer: A Pilot Clinical Trial
Kalanithi Nesaretnam, PhD
Breast Cancer Res. 2010;12(5):R81.
Objective: To determine if tocotrienol Rich Fraction (TRF) in combination with Tamoxifen will improve breast cancer specific survival and recurrence free survival, in women with early breast cancer and estrogen receptor positive tumors.
Study Type: Interventional
Study Design: Non-randomized, double-blind
Subjects: Early Breast Cancer Patients
Intervention: Tocotrienol Rich Fraction, placebo plus tamoxifen
Primary Outcome: The primary end point was breast cancer specific survival, defined as the time from minimization to death due to breast cancer.
Secondary Outcome: The secondary end points included disease free survival, biochemical parameters, liver function and plasma levels of vitamin E.
Methodology: The study is a double-blinded, placebo controlled trial of TRF plus tamoxifen versus placebo plus tamoxifen in women with primary breast cancer for five years. Both the TRF and placebo drugs were prepared and supplied by Hovid Sdn Bhd, Malaysia. Hovid Sdn. Bhd. absolutely did not have any influence in the trial designing, patient recruitment, data collection, analysis and reporting. The placebo drug which contained soy oil without tocotrienols had similar appearance and taste as the TRF drug. A total of 240 women breast cancer patients were assigned to two groups by minimization method that balanced treatment groups. The intervention group was given TRF plus tamoxifen, (n = 120) while control group was given placebo plus tamoxifen, (n = 120).
Results: During the five years of study, 8 patients died due to breast cancer while 36 patients developed local or systemic recurrence. Five-yearbreast cancer specific survival was 98.3% (95% confidence interval (CI): 95.9% to 100%) in the intervention group and 95%, (95% CI: 91.1% to 98.9%) in the control group, while 5-years disease free survival was 86.7% (95% CI: 80.6% to 92.8%) and 83.3% (95% CI: 76.6% to 90.0%), respectively. Risk of mortality due to breast cancer was 60% (HR: 0.40; 95% CI: 0.08 to 2.05) lower in the intervention group versus the controls following adjustment for age, ethnicity, stage and lymph node status but this was not statistically significant. Adjuvant TRF therapy was not associated with breast cancer recurrence (HR: 0.84; 95% CI: 0.43-1.65).
Conclusion: From the current study, there seems to be no association between adjuvant tocotrienol therapy and breast cancer specific survival in women with early breast cancer.