In 2004, Life Extension reported on a Phase III study showing that men with metastatic prostate cancer who received an immune-boosting vaccine called Provenge™ were eight times more likely to live six months without disease progression than those who did not receive the vaccine.1 This anti-cancer vaccine, however, was effective only in men with a Gleason score of 7 or less. (Higher Gleason scores are indicative of a more aggressive type of prostate cancer.)
The FDA refused to accept the study results because the agency does not allow retrospective analysis of a subgroup that may have benefited from an experimental drug. To gain FDA approval, Dendreon, the company testing the vaccine, was forced to begin a new study on men with Gleason scores of 7 or less. However, Dendreon continued to follow patients in the original study, and the results continue to be impressive. Of the 75 patients who entered the trial with a Gleason score of 7 or less, those receiving Provenge™ were 3.7 times more likely to be alive after 30 months; this translates into 53% of the Provenge™ group staying alive compared to only 14% of the placebo group. The Provenge™ group also remained pain-free twice as long on average as the placebo group.
A Wall Street Journal editorial commented on the FDA’s deplorable delay by stating:
“We know that it works, and we know why it works. In any rational regulatory environment, that would be reason to speed Provenge™ to market. But this is the FDA we are talking about.”2
Fast forward to 2005, and the results of a new clinical study on Provenge™ show that three times as many advanced prostate cancer patients who received Provenge™ were alive compared to patients receiving a placebo.3 This study evaluated 127 patients with prostate cancer that did not respond to androgen-deprivation therapy (that is, hormone-refractory prostate cancer). Cancer experts consider this patient subset to have a dismal prognosis, with most dying of the disease within a few years. In the Provenge™ study, 34% of the patients receiving Provenge™ were still alive after three years compared to only 11% of men who were randomly assigned a placebo.3
Under FDA regulations, pros-tate cancer patients with such a dire prognosis had to risk receiving no therapy (the placebo) in the hope that they might be lucky enough to be in the study arm that received the promising drug (Provenge™). Life Extension has advocated that cancer patients with advanced disease should not have to risk receiving a worthless placebo. Historical controls could be used instead of placebos to spare such patients almost certain death.
Prostate cancer kills more than 30,000 American men every year.3 Provenge™ has clearly demonstrated that it improves survival rates, yet the FDA still has not approved it. Considering that the FDA could have approved Provenge™ as early as 2002, the agency’s delay in approving this one drug alone may have resulted in the premature death of tens of thousands of men.
1. Available at: http://investor.dendreon.com/ ReleaseDetail.cfm?ReleaseID=93517&Header=News. Accessed March 17, 2005.
Gamma tocopherol, a member of the vitamin E family, helps kill prostate cancer cells, according to a recent report in the Proceedings of the National Academy of Sciences.*
Previous studies indicate that dietary and environmental factors contribute to some cases of prostate cancer, while antioxidants such as vitamin E may mitigate risk. In a study conducted at the Children’s Hospital Oakland Research Institute in California, the addition of gamma tocopherol to prostate cancer cell cultures not only inhibited cell proliferation but also caused cell death.
The vitamin E family comprises at least eight structurally related forms, all of which are potent antioxidants. Alpha tocopherol is the most abundant form of vitamin E in the human body and in nutritional supplements, while gamma tocopherol dominates dietary sources. Importantly, alpha tocopherol supplementation suppresses gamma tocopherol levels in the body.
In the Children’s Hospital study, gamma tocopherol demonstrated inhibitory effects on prostate cancer cells. Gamma tocopherol was even more potent in combination with another form of vitamin E called delta tocopherol. Together, the two forms of vitamin E produced cell death in hormone-sensitive—but not hormone-resistant—prostate cancer cells. Moreover, gamma tocopherol had no negative effects on normal prostate cells.
Gamma tocopherol exerted effects on prostate cancer cells by blocking sphingolipid metabolism, rather than through its antioxidant action. Sphingolipids are major structural components of cell membranes that mediate cell cycle control and cell death. By blocking the pathway for sphingolipid metabolism, gamma tocopherol deprives cancer cells of this required compound, ultimately leading to cell death.
The study results indicate that certain forms of vitamin E may be useful in preventing and treating some cancers.
—Linda M. Smith, RN
* Jiang Q, Wong J, Fyrst H, Saba JD, Ames BN. Gamma-tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis. Proc Natl Acad Sci USA. 2004 Dec 21;101(51):17825-30.
A European judge declared a proposed ban on thousands of herbal, vitamin, and food supplements “invalid” in a recent ruling. Advocate General Leendert Geelhoed of the European Court of Justice in Luxembourg said the proposed health food directive infringed upon European Union (EU) principles of “legal protection, legal certainty, and sound administration.” The court will deliver a final verdict in June 2005.
EU governments approved the Food Supplements Directive in 2002, but gave manufacturers until July 12, 2005, to submit scientific evidence supporting the safety of their ingredients. Once approved, these ingredients and products would be added to a “positive list” of substances permitted for use in health foods. Such legislation would threaten at least 5,000 products containing more than 200 nutrients, including vitamins, minerals, and plant extracts.
The decision in Luxembourg follows protests from hundreds of doctors and scientists, as well as a legal challenge from the British health food industry. The British Health Foods Manufacturers Association, the National Association of Health Stores, and the Alliance for Natural Health argued that the proposed law was unnecessary and that the cost of compliance would be prohibitive for many small firms with a long history of making safe products. Approximately one third of British women and one fourth of men in the UK use supplements estimated to be worth at least $627 million yearly in US dollars.
The opinion from the Advocate General is not legally binding on the rest of the European Court judges, but is followed by the full court in the majority of final rulings.
—Elizabeth Wagner, ND
Soy isoflavones, a type of phytoestrogen, lower fasting blood glucose and insulin levels in postmenopausal women, according to a study conducted at the National Taiwan University Hospital.1
Soy isoflavones are a popular alternative to synthetic hormone replacement therapy, with some epidemiological studies suggesting that they help alleviate menopausal symptoms and decrease the risk of cancer and heart disease.2
In their study, Taiwanese researchers found that modest amounts of soy isoflavones are as potent as conjugated estrogen in lowering blood glucose and insulin levels.1 The six-month trial examined two groups of postmenopausal women. One group received 100 mg of isoflavones daily, while the other group received a standard dose of 0.625 mg of conjugated estrogens. Both groups also took 300 mg of calcium a day. The researchers measured fasting glucose and insulin levels at baseline and at three and six months.
Compared to baseline values, fasting glucose and insulin levels declined significantly in both groups. Glucose levels fell to 85% and 83% of baseline levels in the isoflavone and estrogen groups, respectively. Similarly, insulin levels dropped to 67% and 56% of baseline values in the isoflavone and estrogen groups, respectively.
Soy isoflavones appear to protect against aberrant glucose metabolism in postmenopausal women. By lowering blood glucose and insulin levels, soy isoflavones may help protect against metabolic syndrome and diabetes.
—Linda M. Smith, RN
1. Cheng SY, Shaw NS, Tsai KS, Chen CY. The hypoglycemic effects of soy isoflavones on postmenopausal women. J Womens Health (Larchmt). 2004 Dec;13(10):1080-6.