Prostate cancer is the most common solid neoplasm in American men, with more than 200,000 cases diagnosed annually. It is the second cause of cancer-related death, responsible for more than 31,000 deaths each year. All men over the age of 40 are at risk for prostate cancer; however, African-American men have the highest risk of any population in the world (outside of Jamaica). They are 1.5 times more likely to develop prostate cancer and 2 to 3 times more likely to die of the disease than U.S. white men. This translates to 1 in 5 African-American men developing prostate cancer over a lifetime and 1 and 20 dying from the disease. Additionally, prostate cancer occurs at younger age in African American men and progresses more rapidly.

In addition to age, family history, and race, inflammation has been hypothesized to be a major predisposing risk factor for prostate cancer. Studies have shown that non-steroidal anti-inflammatory drugs have inhibitory effects on prostate cancer cells, and epidemiological surveys have confirmed that frequent use of NSAIDS is associated with a reduced risk of prostate cancer.

Current treatment options for prostate cancer include surgery to remove the prostate, radiation therapy, cryotherapy and hormone ablation therapy. A major morbidity of all these therapies is impotence. It affects nearly 80% of men who have radical prostatectomies, 50-65% of men who have radiotherapy and 95% of men treated with cryotherapy.

Chemoprevention is the use of agents that prevent the induction of, inhibit, or prevent the progression of cancers. Prostate cancer has a long latency period, which means that it grows slowly and may exist for years before it is detected or causes symptoms. This is actually advantageous for chemoprevention. Research from Columbia University’s Center for Holistic Urology and elsewhere strongly suggests that if every man who was told to “watchfully wait” entered into a focused chemoprevention program, prostate cancer progression would likely be slowed or stopped for a significant number of men with low risk features. Dr. Aaron Katz, who is the Director of the Center for Holistic Urology, believes that the time has come for abandoning the concept of “watchful waiting,” and instead recommends that at-risk men employ “Active Holistic Surveillance” using dietary strategies and herbal supplements studied at the Center and elsewhere.

Currently, there are no conventional treatments available for prostate cancer prevention. In 2003, the Prostate Cancer Prevention Trial showed that finasteride (Proscar®), a drug that inhibits an enzyme known as 5-alpha-reductase, reduced the risk of developing prostate cancer by 25 percent. However, men who developed prostate cancer while taking finasteride were more likely to have high-grade cancers, which can spread quickly even if the tumors are small. As a result, a Proscar strategy for prostate cancer prevention is now not generally recommended. Although NSAIDS may in theory be of value for prevention, their well-defined adverse effects on the gastrointestinal tract and cardiovascular system side-effects limit long-term use, particularly with men who are more advanced in age.

Holistic approaches which incorporate herbal and nutritional therapies seem to hold the greatest promise for prostate cancer prevention. Commanding the most attention is lycopene (a phytonutrient abundant in cooked tomatoes), pomegranate, vitamin D, vitamin E, selenium, and, of course, Zyflamend®, a blend of ten herbs and spices, including green tea, ginger, rosemary and turmeric, uniquely formulated to promote a healthy inflammation response.

Four years ago, under the direction of urologist Dr. Aaron Katz, Columbia University’s Center for Holistic Urology began to research Zyflamend. It was shown to induce programmed cell death, or apoptosis, in LnCap cells, an androgen-dependent prostate cancer cell line. Additional research conducted at MD Anderson Cancer Center has demonstrated that Zyflamend also induces apoptosis in PC3 cells, an androgen-independent and hence more aggressive prostate cancer cell line. Dr. Katz and his colleagues also discovered that while Zyflamend demonstrates cyclooxygenase-2 (COX2) inhibitory activity, its apoptotic inducing effects on prostate cancer cells may occur via multiple COX-independent mechanisms. A summary of the preclinical Zyflamend research was published in the October 2005 issue of the Journal of Nutrition and Cancer.

Encouraged by his impressive laboratory findings, Dr. Katz launched an IRB-approved phase I human clinical trial on Zyflamend in September of 2004. The study is the first human clinical trial to determine if an herbal approach can be used to prevent prostate cancer. Currently, all subjects have been enrolled in the 18-month study (the study closure date was May 4, 2006), and some have even completed the study. To be eligible for the study, the men were required to be between the ages of 40-75 and to have a diagnosis of prostatic intraepithelial neoplasia (PIN) made on biopsy within the past six months. PIN is characterized by rapidly dividing prostate epithelial cells which have begun to lose their normal architecture. These misshapen cells are in a state of early mutation, and they are widely recognized as to be a precursor to prostate cancer. Men who have prostate cancer have areas of PIN in their prostates in more than 85 percent of cases, and it can appear up to 10 years before a diagnosable cancer. According to the AUA, the conversion rate of PIN to prostate cancer is 30-60% over 18 months. Since allopathic medicine offers no preventative treatments, men diagnosed with PIN are prescribed a regimen of “watchful waiting.” Dr. Katz believes this 18 month period provides a critical opportunity for dietary, lifestyle and herbal interventions like Zyflamend, and as aforesaid recommends Active Holistic Surveillance in lieu of watchful waiting.

All subjects in the Zyflamend trial have been assigned to a cohort and placed on a successive herbal supplement regimen starting with Zyflamend dosed at 1 gelcap three times a day with meals. They are assessed for safety and toxicity every three months. The assessment includes patient history, physical exam, and routine blood tests. To ensure the treatment is having no adverse effects on cardiovascular function, an EKG is performed every six months. The subjects are further assessed for efficacy via repeat biopsy every six months as well.

Dr. Katz has presented preliminary findings from the Zyflamend study at the National Cancer Institute and other scientific meetings. He reports that to date 29 patients have been enrolled in the study, however, five have withdrawn. The median patient age is 64.95 years (46.82-75.42) with a median PSA level of 5.7 (0.4-35.1). There have been no adverse events reported or toxicities apparent, and all subjects are 100% compliant. A total of 47 biopsies have been performed in 23 patients. These data are preliminary, and more data will be obtained over the next year. Of these biopsies to date, 90% of the biopsies have been negative for prostate cancer and 60% have actually reverted back to normal prostate tissue. Of the seven patients who have completed the 18-month trial, three tested negative for both PIN and prostate cancer at their final 18-month visit, 3 were positive for PIN and 1 was positive for both PIN and prostate cancer. Accordingly, only 1 of 7 subjects developed prostate cancer at the completion of the study (14%), vs. the 30-60% that would normally be expected. Additionally, 50% of patients have had a decrease in prostate specific antigen (PSA), and 27% of patients have had their PSA decrease by at least half. In total, five patients out of the twenty-nine who began the trial have developed cancer, but their tumors are very small (in all cases in only one biopsy core, with less than 5% of tissue indicating cancer) and in an early, non-aggressive state (Gleason Score of 6). In other words, even these five subjects who converted to cancer remain excellent candidates for Active Holistic Surveillance in lieu of more interventional procedures.

Two case reports have been submitted for publication and/or presented at scientific meetings. The first highlights a 66-year-old African-American male who has completed the trial. He had a positive family history of prostate cancer and was found to have multiple areas of PIN on initial biopsy. Six months into the trial, the biopsy came back negative for both PIN and cancer. Biopsies at both 12 and 18-month follow-up visits confirmed that the subject was free of both cancer and PIN – in other words, his tissue had reverted to normal. Additionally, the subject’s PSA decreased from 6.3ng/ml at the start of the study to 4.2ng/ml at the end, and immunohistochemical staining of the prostate tissue for NFKappaB, a gene-activating factor that is over-expressed in many cancers, has provided an impressive visual image of tissue changes that may occur while taking Zyflamend at the prescribed dosage.

A second case report features a 70-year-old African-American male who initially presented with an elevated PSA of 9.7ng/ml and high-grade PIN in 1 of 12 cores biopsied. Throughout the study the patient’s mean PSA was 8.93ng/ml. Six months into the trial, his biopsy revealed benign prostatic hyperplasia (BPH) only. The 12 and 18 month biopsies also revealed that the patient was negative for both prostate cancer and high-grade PIN. COX2 stains of the sampled prostate tissue performed at the end of the study were also found to be negative.

The phase I Columbia-Zyflamend clinical trial will be complete sometime in 2007. In the meantime, the preliminary results are providing men and their doctors with hope and encouragement that has been previously unavailable. Pending design is a phase II trial, which will evaluate the efficacy and safety of Zyflamend in a larger group of men, with special focus on the African American community.