Among patients with castration-resistant prostate cancer, the addition of hormone therapy following vaccine treatment improved overall survival compared with either treatment alone or when the vaccine followed hormone treatment, according to recent data published in the July 15 Clinical Cancer Research, a journal of the American Association for Cancer Research.

Philip M. Arlen, M.D., director of the Clinical Research Group for the Laboratory of Tumor Immunology and Biology, Center for Cancer Research, at the National Cancer Institute, said the findings have important implications for guiding treatment decisions for prostate cancer patients.

“Vaccines, if and when they are approved, can be safely and effectively combined with other therapies, including hormones,” said Arlen.  “There appears to be an advantage in overall survival.”

Arlen and colleagues enrolled 42 patients who had castration-resistant prostate cancer.  These patients were randomly assigned to receive either a poxvirus-based prostate-specific antigen vaccine or hormone therapy with nilutamide.  At progression, patients received the other therapy and continued to receive their original therapy.

For all the patients enrolled in the study, the three-year survival probability was 71 percent and the median overall survival was 4.4 years.  Patients randomized to the vaccine had a three-year survival probability of 81 percent and an overall survival of 5.1 years, while patients taking nilutamide had a three-year survival probability of 62 percent and an overall survival of 3.4 years.

Of the 42 patients in the study, 12 patients who were originally assigned to vaccine switched to nilutamide plus vaccine and eight patients who were originally assigned to nilutamide switched to vaccine plus hormone, due to rising levels of prostate-specific antigen with no evidence of metastasis.  For patients who received vaccine and then nilutamide, the three-year survival probability was 100 percent with a median overall survival of 6.2 years.  For patients who switched to the vaccine after hormone, the three-year survival probability was 75 percent with a median overall survival of 3.7 years.

Arlen said the hormone therapy in combination with the vaccine works in two ways.

“By using hormone therapy in prostate cancer you can help enhance your T-cell response to where the cancer is in the prostate gland, and you are also more likely to achieve a better immune response,” said Arlen.

Building on the results of this phase II study, researchers have developed another generation of this vaccine by adding molecules which boost T-cell responses.

Based on the current pace of vaccine research overall, Arlen predicts that men with prostate cancer could potentially see an effective, new treatment vaccine within the next several years.

“Phase II trials such as this one are adding to our knowledge, and other phase III trials are getting ready to publish their data,” said Arlen.  “If the phase II data hold up in phase III trials, we could see a new treatment vaccine within a few years.”

A great deal of attention has been paid to the use of growth hormone (hGH) by elite athletes and a few vocal entertainers. But underlying this tip of the iceberg is a $2 billion dollar a year business, likely involving hundreds of thousands of regular people, and promoted by anti-aging and age-management clinics and compounding pharmacies who aggressively market and sell growth hormone with the claim that it has anti-aging or athletic enhancing properties. Since their previous article in the Journal of the American Medical Association (JAMA) in 2005 on the clinical and legal aspects of growth hormone for anti-aging, in which researchers from Boston University School of Medicine, Boston Medical Center and the University of Illinois at Chicago alerted the medical community and lay public to the deceptive mass marketing and illegal distribution of growth hormone for anti-aging and athletic enhancement, the authors provide new evidence demonstrating that these deceptive and dangerous activities have grown worse.Remarks Dr. Thomas Perls, Director of the New England Centenarian Study and an associate professor of Medicine at Boston University School of Medicine, who has monitored the anti-aging industry for over the past ten years, “despite the overwhelming evidence that the risks and dangers of growth hormone far outweigh the clinically demonstrated insignificant benefit in normally aging individuals, the prescribing, distribution and sale of hGH for alleged anti-aging aesthetic and athletic enhancement has dramatically grown over the past few years. Clearly, the coordinated and aggressive marketing campaigns of the anti-aging and age-management industries are highly and most unfortunately effective.”

Clinical evidence does support the therapeutic use of hGH for children and adults with appropriate clinical indications. However, these cases are disease specific and rare. Furthermore, any effectiveness that is demonstrated in the rare medical conditions approved for hGH distribution cannot be translated into effectiveness among healthy aging adults, a deceptive assertion often made by proponents of hGH use for a wide range of panacea-like benefits.

In January, 2007, the FDA issued an alert emphasizing that prescribing and distributing hGH for anti-aging and body building is illegal. A number of high-profile government investigations such as Operations Raw Deal, Phony Pharm and Which Doctor have attempted to make a dent in the illegal distribution of hGH and anabolic steroids for unapproved uses such as anti-aging or aesthetic reasons. As stated on the Albany County District Attorney’s website, in the case of Operation Which Doctor, numerous governmental agencies are “working together to take down a nationwide distribution ring of anabolic steroids, Human Growth Hormones and other controlled substances, by targeting the ring’s dirty doctors, its distributors that pose as clinics, and ultimately the ring’s supplier Signature Pharmacy.”

Contrary to published claims, neither long-term safety nor health benefits have been demonstrated in normally aging individuals taking hGH. A review of clinical studies among healthy, normally aging individuals found that hGH supplementation does not significantly increase muscle strength or aerobic exercise capacity. However, documented adverse effects include soft tissue edema, arthralgias (joint pains), carpal tunnel-like syndrome, gynecomastia (enlarged breasts) and insulin resistance with an elevated risk of developing diabetes. Increasingly more and more animal and laboratory studies suggest an increased cancer risk.

The authors suggest that several measures need to be taken to address the inappropriate distribution and use of hGH. Among their recommendations:

• The public must be accurately informed by physicians and scientists who do not have a vested interest in hGH, about health risks, fraudulent marketing and illegal distribution of this drug.
• Organizations that promote or indirectly profit from the medically inappropriate and illegal distribution of hGH that have been accredited by the Accreditation Council for Continuing Medical Education (ACCME) to offer American Medical Association Physician Recognition Award (PRA) category 1 CME credits or other categories of CME credit should, at a minimum, have their accreditation revoked.
• U.S. manufacturers of hGH must be more effective in, and held accountable for, controlling the distribution of the drug to companies providing the drug for illegal uses.
• Congressional hearings and media attention surrounding hGH should focus less on athletes and prominent entertainers who are also victims of deceptive marketing and pushing of hGH, and much more on the distributors who are violating federal and state laws by making the drug available for non-approved uses.
• Senators Schumer and Grassley and Representative Steven Lynch deserve the public’s support of their intention to strengthen and enhance the law regarding the illegal distribution of hGH. ‘Strengthening the law’ should entail stiffer financial and imprisonment penalties for illegally prescribing and/or distributing growth hormone for purported anti-aging, age management, aesthetic enhancement, and body building uses. Enhancing the law should include the addition of sermorlin (growth hormone releasing hormone [GHRH]) and mecasermin (insulin-like growth factor I [IGF-1]) and their analogues. GHRH (which stimulates the release of endogenous hGH) and IGF-I (which mediates many of the effects of hGH) result in hGH-like effects, and, therefore, the potential for their inappropriate use as purported anti-aging and performance enhancement therapies clearly exists.

Perl adds: “In my capacity as a reviewer of medical records seized from anti-aging clinics by the DEA, I almost never see hGH provided in isolation. It is usually a part of a complex cocktail of one or more anabolic steroids, human chorionic gonadotropin (specifically for men to decrease the obvious signs of steroid abuse such as small testicles and enlarged breasts), thyroid hormone, DHEA and other drugs. Additional drugs such as blood pressure medicines, diuretics and insulin may be given to treat the side effects of the basic cocktail.”