In the study of 23 advanced-stage ovarian cancer patients, tocotrienol was administered at a dosage of 300 mg three times a day, with bevacizumab given to patients at 10 mg/kg intravenously every three weeks. Patient disease stabilization was high at 70%, with increased survival, which approximately doubled.
Ovarian cancer is the fifth most common cause of cancer death in women in the U.S. According to the American Cancer Society, approximately 22,240 women in the U.S. received a new ovarian cancer diagnosis, while approximately 14,070 people died of the disease in 2018. Since ovarian cancer is usually not diagnosed until it is more advanced, the 5-year survival rate is only 47%. Patients with advanced-stage ovarian cancer often have a recurrence of the disease after primary treatment, and despite second and third line treatments, these patients eventually become chemotherapy-resistant with few therapeutic options. The goal at this stage is to improve the quality and duration of life with as few side effects as possible.
In 2018, the FDA approved bevacizumab (Avastin), an anti-angiogenic agent, for frontline treatment of ovarian cancer after surgery, based on its ability to reduce disease progression by 38% in a double-blind, placebo-controlled, multicenter study. In Europe, the drug has been used for first-line and recurrent ovarian cancer treatment for much longer, since 2011, and shows similar promising results.
Similar to bevacizumab, tocotrienols, isomers of the vitamin E family, have anti-angiogenic properties that are thought to contribute to the anti-neoplastic effect. Previous in vitro and in vivo studies, including a clinical trial in patients with pancreatic cancer, showed that delta-tocotrienol was especially active against malignancies, compared to other vitamin E isoforms.
The Danish study, led by Dr. Anders Jakobsen at Vejle Hospital, aimed to identify the potential additive effects of bevacizumab and delta-tocotrienol by observing the stabilization and control of disease, progression-free survival (PFS), and overall survival (OS). Although the target level of 75% disease control at six months was not reached, the observed disease control of 50% at six months was high compared to only 25% of disease control when using bevacizumab as a single agent in another study conducted by the same researchers. Even more compelling is the result of a high overall disease control of 70% with a combination of bevacizumab and delta-tocotrienol.
Compared to a typically reported median PFS of 2-4 months and median OS of 5-7 months, combined treatment of bevacizumab and delta-tocotrienol nearly doubled survival, allowing patients to reach a median PFS of 6.9 months and a median OS of 10.9 months. Notably, 25% of the patients were alive after 24 months.
The study treatment was shown to have low toxicity, with only three patients discontinuing their medications due to well-known side effects of bevacizumab therapy. Further, quality of life was stable.
The authors noted that “the present study indicates that the combination of bevacizumab and delta-tocotrienol is effective in multiresistant ovarian cancer.” They also mentioned that, “bevacizumab is used in a spectrum of different tumors and an additional effect by an atoxic drug holds high priority.”
Commenting on the research, Dr. Barrie Tan, president of American River Nutrition said that “as one of the most deadly cancers in women, ovarian cancer needs further attention, and I applaud Dr. Jakobsen and his group for their novel approach in finding alternative treatment options for these patients. The fact that a simple vitamin such as tocotrienol in combination with standard therapy could prolong a woman’s life and improve its quality under these severe circumstances is nothing short of astonishing.”