'Salvage' Prostate Surgery Has Improved
17th. of december 2004: source: Reuters Health 'Salvage' Prostate Surgery Has Improved NEW YORK (Reuters Health) - For men with prostate cancer that recurs after radiation therapy, 'salvage' surgery to remove the prostate can lead to long-term cancer control, New York- based researchers report. Moreover, the side effects of the procedure are "acceptable," the team reports in the Journal of Urology. "Salvage radical prostatectomy is technically demanding, but the procedure can be performed safely by an experienced surgeon," Dr. James A. Eastham told Reuters Health. "Although rates of urinary incontinence and erectile dysfunction are higher than after standard radical prostatectomy, these outcomes continue to improve." Eastham, of Memorial Sloan-Kettering Cancer Center, and colleagues reviewed data from 100 patients who underwent the procedure between 1984 and 2003 following external beam radiation or radioactive seed implants. Between 1993 and 2003, the rate of major complications dropped significantly from 33 percent to 13 percent, and the rate of rectal injury fell from 15 percent to 2 percent. Five years after undergoing the operation, one third of patients were not incontinent, and the majority of the others required one pad daily or less. Moreover, 23 patients who required three or more pads daily became continent after they were fitted with an artificial urinary sphincter. As for erectile difficulties after five years, overall, the potency rate was 28 percent following nerve-sparing radical prostatectomy. However, among patients who were previously potent, 45 percent remained so. Thus, the team concludes that the relatively good outcomes after salvage radical prostatectomy "should persuade more physicians to consider patients for this potentially curative procedure." SOURCE: Journal of Urology, December 2004.

Biocurex's RECAF Blood Test Outperforms PSA For Prostate Cancer Detection
7th. of december 2004: source: BioCurex Biocurex's RECAF Blood Test Outperforms PSA For Prostate Cancer Detection According to the National Cancer Institute, “Most men with an elevated PSA test turn out not to have cancer; only 25 to 30 percent of men who have a biopsy due to elevated PSA levels actually have prostate cancer” [1]. This is because PSA is produced by prostate cells, whether they are malignant or benign and therefore, benign tumors also produce PSA in excess. Therefore, as noted in the Journal of the American Medical Association, PSA is not a suitable marker to screen asymptomatic men for prostatic cancer [2] and yet, for lack of a better test, it is used in regular checkups. The PSA test is not specific enough to screen for prostate cancer. On the other hand, the high specificity exhibited by RECAF tests of prostate specimens, as well as in many other types of cancer, strongly supports the use of RECAF testing for screening. Moreover, combining the PSA and RECAF tests could eliminate the false positives resulting from using PSA testing alone. PSA has the advantage of localizing the problem to the prostate and RECAF could then determine if the high PSA value is due to a cancer. This combination would also facilitate the introduction of RECAF into the market place since PSA testing is very common. The company is discussing such a combination of tests with major healthcare companies and laboratories presently performing PSA tests. PSA projected sales worldwide for 2004 are $450M [3] and prostate cancer represents only 17% of all cancers [4]. Our preliminary results indicate that RECAF works better than PSA for the detection of prostate cancer; and previous data showed that it could be used in most types of cancer. A simple extrapolation suggests a market potential for RECAF of $2.6B per year. To date, BioCurex has reported highly positive results from testing many forms of cancer including prostate, stomach, lung, ovary, breast and colon. These amount to 2/3 of all types of cancers and we believe that RECAF will work as well for the other 1/3 of malignancies. Dr. Moro, BoCurex’s CEO, stated: “We are extremely happy to report these results, which were obtained with a new version of the company’s blood cancer detection assay. This improved test uses monoclonal antibody technology, for which Milstein and Kohler received the Nobel price in 1984. Monoclonal antibodies offer many significant advantages over the conventional antiserum test we were using previously to prove the RECAF concept. Monoclonals are far more specific, they are very consistent from one batch to another and they are easy to produce in industrial quantities using tissue culture techniques.” The American Cancer Society estimates that over 220,000 men will be diagnosed with prostate this year in the U.S. with 29,000 deaths attributable to prostate cancer. The company also wishes to advise that it is continuing its efforts to re-establish itself for quotation on the NASD OTC:BB. The process is not a direct one but the company is committed to the goal of achieving a more advanced listing. We appreciate the patience of our investors at this time and we will provide the investment community with appropriate updates as they occur. BioCurex is also progressing with its plan to license its RECAF technology. A licensing agreement would allow the company to work with healthcare companies experienced in the cancer diagnostic arena and allow BioCurex to benefit from their scientific and business expertise. To read more about the Company, please visit the News section in our web site (www.biocurex.com). About BioCurex: BioCurex, Inc. is a biotechnology company that is developing products based on patented/proprietary technology in the area of cancer diagnosis. The technology identifies a cancer marker known as RECAF[TM], which is found on malignant cells from a variety of cancer types but is absent in most normal or benign cells. To find out more about BioCurex (OTCBB: BOCX), visit our website at www.biocurex.com. Note: The Company has not authorized the release of this information in any form that contravenes the Communication Act and will not be responsible for unsolicited massive distribution of this material by e-mail or facsimile by unauthorized parties. Statements in this press release, which are not historical facts, are “forward-looking statements'' within the meaning given to that term in the Private Securities Litigation Reform Act of 1995. The Company intends that such forward-looking statements be subject to the safe harbors created thereby. Since these statements involve risks and uncertainties and are subject to change at any time, the Company's actual results could differ materially from expected results. Contact: Ricardo Moro, BioCurex, Inc., Tel: (604) 207 9150 References: [1] Source: http://cis.nci.nih.gov/fact/5_29.htm [2] Source : MD Krahn et al, Journal of the American Medical Association (JAMA), 1994 Sep 14;272(10):773-80. [3] Source: The Worldwide Market for Cancer Diagnostics, November 2002. Market report published by Kalorama Information (http://www.kaloramainformation.com) [4] Source: American Cancer Society, Cancer Facts and Figures 2004 (http://www.cancer.org/docroot/STT/content/STT_1x_Cancer_Facts__Figures_2004.asp)

Prostatectomy using the DaVinci Robotic System a good way of surgery for patients with prostate cancer.
7th. of december 2004: source: VanderBilt Hospital Prostatectomy using the DaVinci Robotic System gives better possibilities for patients with prostate cancer and far less side effects. If you go to this website you may watch also a videotape how the robotic system functions. Very interesting in our opinion. In Belgium - Bruxelles and the Netherlands - Rotterdam and Amsterdam is also a robotic system used for also other types of cancer like lungcancer and inoperable pancreascancer e.g. Watch here the robotic system in the VanderBilt hospital: www.vanderbilt.com

Antisoma Telomere Targeting Agent Stops Tumour Growth In Prostate Cancer Model
4th. of november 2004: Source: Roche and Antisoma.
Antisoma Telomere Targeting Agent Stops Tumour Growth In Prostate Cancer Model

| LONDON, Nov. 4, 2004 (PRIMEZONE) -- Cancer drug developer Antisoma today presents new data showing that one of its telomere targeting agents (TTAs) rapidly blocks prostate tumour growth in a human xenograft model. While in untreated control animals tumours grew to lethal size within 10 days, animals given the TTA experienced a halt in tumour growth at around day 7 and survived to the experiment's end on day 25. These findings extend the range of cancers shown to be susceptible to Antisoma's TTAs and demonstrate that the drugs have profound effects on tumour growth even when used as a sole treatment.

The presentation will be given by Antisoma's Head of Research, Professor Lloyd Kelland, at the AACR Special Conference on The Role of Telomeres and Telomerase in Cancer in San Francisco. It comes as the Company, working with the Cancer Research UK Group led by Professor Stephen Neidle at the London School of Pharmacy, nears completion of work to select a lead candidate from the TTA programme for clinical trials.

Professor Kelland commented "What's really exciting about these TTAs is the speed of their anti-tumour effects. We're not having to wait for many rounds of cell division before the effects kick in, which was a major concern with earlier drugs that were pure telomerase inhibitors."

Except for the historical information presented, certain matters discussed in this statement are forward looking statements that are subject to a number of risks and uncertainties that could cause actual results to differ materially from results, performance or achievements expressed or implied by such statements. These risks and uncertainties may be associated with product discovery and development, including statements regarding the company's clinical development programmes, the expected timing of clinical trials and regulatory filings. Such statements are based on management's current expectations, but actual results may differ materially.

About telomere targeting agents (TTAs)

Antisoma has three drugs in clinical trials and three priority preclinical projects, one of which is the TTA programme. The TTAs under development at Antisoma were invented by Professor Stephen Neidle at the Institute of Cancer Research and the London School of Pharmacy. They were licensed by Antisoma through Cancer Research Technology, which is part of Cancer Research UK.

Telomeres are protective regions found at the ends of chromosomes (the structures into which DNA is packaged in each cell of the body). In normal cells, they shorten slightly with each round of cell division until they become critically short, causing the cell to enter the self-destruct programme of apoptosis. Most cancer cells make the enzyme telomerase, which maintains the length of telomeres and allows the cells to avoid apoptosis. A number of drugs have been developed that inhibit telomerase. These are generally characterised by a slow onset of action because they require rounds of cell division to 'run down' the telomeres to the point where apoptosis ensues. TTAs by contrast act more rapidly, binding to the telomere itself and destabilising it. One clear effect is the uncapping of chromosome ends leading to lethal end-to-end chromosome fusions. The action of TTAs is believed to involve prevention of telomerase binding to the telomere. However, it must have other facets because the drugs show broad effectiveness against cancer cell lines, including the minority that use alternative, non-telomerase mechanisms to maintain their telomeres.

About Antisoma

Based in London, UK, Antisoma is a biopharmaceutical company that develops novel products for the treatment of cancer. The Company fills its development pipeline by acquiring promising new product candidates from internationally recognised academic or cancer research institutions. Its core activity is the preclinical and clinical development of these drug candidates. Antisoma forms partnerships with pharmaceutical companies to bring its products to market. In November 2002, Antisoma formed a broad strategic alliance with Roche to develop and commercialise products from Antisoma's pipeline. Please visit our website for further information about Antisoma.

Dendreon's Provenge Extends Survival in Advanced Prostate Cancer.
12th. of january 2004: Source: Dendreon - DOW -- PRESS RELEASE: Dendreon's Provenge Extends Survival in Advanced Prostate Cancer -- SEATTLE--(BUSINESS WIRE)--Jan. 12, 2004-- Results from ongoing monitoring of Company's completed D9901 Phase 3 trial is longest survival benefit seen in late-stage prostate cancer. Dendreon Corporation (Nasdaq:DNDN) today announced updated survival data from patients with advanced prostate cancer with Gleason Scores of seven and less who participated in its completed and previously reported Phase 3 trial (D9901) of Provenge(R), the Company's investigational immunotherapy for the treatment of prostate cancer.
Patients with Gleason Scores of seven and less receiving Provenge had a significant survival advantage, having on average an 89 percent overall increase in their survival time as compared to placebo (log rank p = 0.047, hazard ratio = 1.89). This benefit is reflected by a prolongation in the median survival time in patients receiving Provenge by 8.4 months (30.7 months versus 22.3 months).
At 30 months from randomization, the survival rate for Provenge-treated patients is 3.7 times higher than for patients receiving placebo (53 percent versus 14 percent, p = 0.001).
Consistent with previous reports, a majority of those patients in D9901 who are still alive have received treatment with Provenge and will continue to be followed according to the study protocol. The Company expects to present this as well as other updated data at major scientific meetings throughout the year.
Prostate cancer is the most common non-skin cancer in the United States. More than one million men in the United States have prostate cancer, with an estimated 220,000 cases diagnosed and 28,900 deaths in 2003.
"This is the longest survival benefit ever reported in a Phase 3 study in late stage prostate cancer," said Dr. John M. Corman Director of the Virginia Mason Comprehensive Prostate Cancer Clinic and Assistant Clinical Professor of Urology at the University of Washington in Seattle. "With the combination of this exciting new survival data and favorable side effect profile, Provenge has the potential to change the way we treat prostate cancer in the future."
These updated survival data are consistent with other previously reported data from the D9901 trial that showed significant clinical benefit from Provenge treatment for men with a Gleason Score of seven and less. For these men, the average time to disease progression is more than two-fold longer than that for patients treated with placebo (p = 0.001) and the average time to experiencing cancer-related pain is more than 2.5 times longer than that for patients treated with placebo (p = 0.016). Treatment was well tolerated, with mild infusion-related fevers and chills the most common adverse events. As previously reported, no benefit has been seen in men with Gleason Scores of eight and higher.
Last year, Dendreon also released data confirming Provenge's mechanism of action based on T-cell mediated immune response. These data showed that among men treated with Provenge, those with a Gleason Score of seven and less demonstrated a T-cell mediated immune response 7-fold greater than men with a Gleason Score of eight or more (p = 0.0065).
"Based on the strength of this survival data, which is consistent with all of the data gathered to date on our other endpoints in the trial for patients with Gleason Scores of seven and less, we are more enthusiastic than ever regarding the pivotal role that Provenge may play in providing a new and well tolerated targeted therapy for prostate cancer patients," said Mitchell H. Gold, M.D., president and chief executive officer of Dendreon. "The results from this study represent an important milestone in the fight against prostate cancer and indicate that Provenge may provide for a well-tolerated treatment option that offers patients a potential survival advantage."
The ongoing, pivotal D9902B Phase 3 trial of Provenge is based on the knowledge gained from the results of D9901. The study is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA. Provenge also has Fast Track designation. The pivotal double blind, placebo-controlled D9902B trial is now underway at leading cancer centers around the country. To be eligible for the study, patients must have metastatic prostate cancer that has progressed following hormone therapy and have a Gleason Score of seven and less. Patients must also be free of cancer-related pain. About Provenge
Provenge is designed to stimulate a man's immune system against prostate cancer. It is developed through Dendreon's proprietary Antigen Delivery Cassette(TM) technology, which utilizes a recombinant form of an antigen found in 95 percent of prostate cancers, prostatic acid phosphatase (PAP). About Gleason Score
The Gleason Score is the most commonly used prostate cancer scoring system and is considered one of the most important prognostic indicators for prostate cancer. The score is based on tissue findings throughout the prostate that correlate with the aggressiveness of a tumor. High Gleason Scores are indicative of aggressive cancers and are not associated with a favorable prognosis. In the androgen independent patient population approximately 75 percent of the patients have a Gleason Score of seven and less.

PC-Spes and Prostasol, A mix of Chinese herbs is effective for prostate cancer.
PC-SPES and Prostasol can be ordered at Medpro - Scherpenzeel - Netherlands Address: Medpro Holland B.V. Dorpsstraat 182 3925 KG Scherpenzeel Phone: +31 33 2867642 Fax: +31 33 2867647 Email product information: information@med-pro.org Email office: office@medpro.org October 2000: Source: Journal of oncology HERBAL THERAPY PC-SPES: IN VITRO EFFECTS AND EVALUATION OF ITS EFFICACY IN 69 PATIENTS WITH PROSTATE CANCER ALEXANDRE DE LA TAILLE, RALPH BUTTYAN, OMAR HAYEK, EMILIA BAGIELLA, AHMAD SHABSICH, MARITH BURCHARDT', TATJANA BURCHARDT, DOMINIQUE K CHOPIN AND AARON E. KATZ
The Journal of Urology Vol. 164, 1229-1234, October 2000

From the Squier Urilogical Clinic, Department of Urology, Columbia University College Of Physicians and Surgeons, Columbia-Presbyterian Medical Center and Department of Biostatic, Columbia University, School of Public Health, New York, New York and
Department of Urology, Henri MondorHospital, Creteil, France.
ABSTRACT: Purpose: We investigate the potential use of the phytotherapeutic PC-SPES to treat human prostate cancer, and evaluate its in vivo and in vitro activity, and clinical efficacy.
Materials and Methods: PC-SPES was evaluated for its ability to induce apoptosis on prostate cancer cell lines LNCaP, PC3 and DU145. The effect of oral PC-SPES on growth of PC3 tumors present in male immunodeficient mice was studied. A total of 30 male nude mice were divided in 5 groups. In groups 1 control and 2 full dose therapy was started the sarne day of the tumor injection. In groups 3 control, 4 half dose and 5 full dose PC-SPES therapy was initiated 1 week after tumor injection. A total of 69 patients with prostate cancer were treated with 3 capsules of 320 mg PC-SPES daily. Serum prostate specific antigen (PSA) responses and side effects were evaluated.
Results: All of the cultured prostate cancer cell lines had a significant dose dependent induction of apoptosis folIowing exposure to an alcoholic PC~SPES extract. Immunodeficient mice xenografted with the PC3 cell line had reduced tumor volume compared with sham treated controls when they were treated with a PC-SPES extract from the time of tumor cell implantation (931 ± 89 versus 1,424 ± 685 mm. p not significant) but not when the treatrnent was hegun 1week after tumor cell implantation. The testis, prostate, bladder and seminal vesicles of the treated mice were sigificantly reduced in weight compared with the sham treated animals. Of the patients with prostate cancer 82% had decreased serum PSA 2 months, 78% 6 rnonths and 88% 12 months after treatrnent with PC-SPES. Side effects in the treated patient population included nipple tenderness in 42% and phlebitis requiring heparinization in 2%.
Conclusions: An extract of the phytotherapeutic agent PC-SPES proved to be active in inducing apoptosis of hormone sensitive and insensitive prostate cancer cells in vitro, and in suppressing the growth rate of a hormone insensitive prostate cancer cell line in vivo. The overwhelming majority of patients with prostate cancer treated with the agent experienced a decrease in serum PSA but also demonstrated a side effect profile comparable to estrogen treatmeant

Key Words: prostatic neoplasms; hormones; medicine, herbal; prostate~specific antigen

Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of male cancer deaths.¹ Epidemiological studies in the United States and other countries suggest a strong dietary factor in the development of prostate cancer.² Such statistics also suggcst that dietary agents may have efficacy in preventing the occurrence or progression of this disease. These findings support the search for dietary or herbal agents that could be used In a combined regimen with contemporary' therapeutics to treat patients with prostate cancer. The concept of herbal therapies is popular with the patient population1 and recent estimates suggest that some form of complementary therapy has been used by 27% of patients with prostate cancer.3
Of the more exciting herbal therapies that are currently being used to treat prostate cancer is the herbal amalgam PC-SPES. Phytotherapeutics, which are extracts of plants and herbs have been used to treat prostate disease for several years. PC-SPES has been commercially available since November 1998 and is a combination of 8 different herbs. Each herb individually seems to have some antitumoral effect. Isatis indigotica contains ß-sitosterol, which is a phytosterol that is a constituent of legumes (bean family). Oral consumption of ß-sitosterol has been shown to reduce cancer growth in animal studies. Glycyrrhiza glabra and glycyrrhiza uralensis are Chinese herbs that contain saponin and quercetin. There is some evidence that saponin can stimulate the immune system, and quercetin has demonstrated anti cancer effects. This herb lowers serum testosterone levels and increases estrogen levels by inducing the enzymes 17 ß-hydroxysteroid dehydrogenase and aromatase.5 Panax pseudo-Ginseng contains dammaranc type saponins that are adaptagenic (possess nonspecific, antistress, homeostasis inducing properties), and is purported to enhance immunity by stimulating activity of natural killer cells. Ganoderm lucidum contains high moleculair weight polysaccharides and inhibits the growth of sarcoma. Scuttellaria baicalensis can. inhibit the growth of sarcoma and cervical cancer cell lines in vitro. The saponin Baicalein inhibits cancer cell multiplication and induces apoptosis in vitro,7 and has been shown to stimulate the immune system in vivo and possess antibacta-rial effects, dendranthema morifolium is less known with unspecified biological effects.
Rabdosia rubesrens has multiple antitumor and analgesic effects and inhibits in vitro sarcoma cells, hepatoma cells, cervical cancer cells and lymphoma11 Analgesis and anti-anorexigenic properties have been observed in patients with primary liver cancer who received this therapy.11'

Accepted for publication April 14, 2000.
Supported by Grant R0ICA70769 from the Natiorial Institutes of Health and the National Cancer Institute, Washington, D. C.

Editor's Note. This article is the fifth of 5 published in this issue for which category 1 CME credits can be carned. Instructions for obtaining credits are given with the questions on pages 1356 and 1357.

Saw palmetto is a natural product that decreases the bioavailability of testosterone in vivo and inhibits production of eicosanoids, which are Substances produced during inflammation. This herb has also been demonstrated to have en effect on the symptoms of patients with benign prostatic hyperplasia.13 To assess the potential efficacy and determine the effects of PC-SPES we performed experiments on cultured prostate cancer cells (PC3) previously reported that an alcoholic extract of PC-SPES was able to reduce significantly the growth rate of prostate cancer cell lines LNCaP, PC3 LNCaP DU145.14 To assess whether this effect was due to a simple reduction in the rate of growth or tumor cell viability, we tested the potential of PC-SPES extract to induce apoptosis of these cell lines. Also, we studied whether PC-SPES therapy affects prostate cancer cells (PC3} grown as xenograft tumors in Immunodeficient mice. Finally, we report our clinical experience with PC-SPES in patients with. prostate cancer.

MATERIALS AND METHODS
Prostate cancer cell line experiment. We tested the possibility that PC-SPES can induce apoptosis on human prostate cancer cell lines PC3, LNCaP and DU145. The cells were grown in RPMI-1640 medium supplemented with 10% fetal bovine serum, 2 mM. glutamine and 1x antibiotic/antimycotic solution (20 ug/ml streptomycin sulfate, 20 unit per ml. penicillin and 0.2S ug./mL amphotericin B). The cells were incubated at 37C in a humidified atmosphere of 5% carbon dioxide and 95% air. Cells were exposed for 8 days to PC-SPES at 2 concentrations of 4 ul. PC-SPES extract per ml. medium and 8 ul PC-SPES per ml. medium. A control was done using the same 4 and 8 ul volume of ethanol 70%,
After 5 days of exposure the medium was removed and centrifuged. to collect cells in the medium, and trypsin was used to collect adherent cells. All cells were collected in the same tube, centrifuged on a slide and fixed on the slide with perafolmaldehyde 4% for 10 minutes. Apoptotic body staining procedure was performed as recommended by the manufacturer using the in situ call death detection kit, phospha-tase alkaline TUNEL assay. Analysis of variance (ANOVA) was used to test the overall difference between. PC-SPES and the control. Separate analyses were conducted for the different call lines. Commercial software was used and p = 0.05 was considered significant.
Tumor xenografts. A total or 30, 6-week-old athymic male nude mice were housed aseptically 5 per cage- Mice were sterilely inoculated subcutaneously bilaterally with 1.5 million PC3 cells (hormone rafractory prostate cancer cell line) in 0.25 ml. basement rnembrane matrix and randomly divided into & groups of 6. PC-SPES therapy was initiated the same day as tumor injection in group 1- no PC-SPES and group 2-PC-SPES at 300 mg./kg. daily. PC-SPES therapy was initiated 1 week after tumor injection in group 3- no PC-SPES, group 4 - PC-SPES at a half dose of 150 mg/kg. daily and group 5 - PC-SPES at a full dose of 300 mg-/kg. daily.
PC-SPES herbal preparation was administered as a suspension in 1,5% carboxymethylcellulose with 0.2% Tween 20 for 5 days a week as reported previously.15'16 In the control groups only the solution containing carboxymethylcellulose and Tween 20 was administered. The dose was based on body surface area of patients with prostate cancer taking PC-SPES. Tumors were measured twice a. week starting at week 4 with vernier calipers and calculated by the formula length x width X height: X 0.5S36. At 2 months after tumor infection bromodeoxyuridine was injected in the peritoneum 2 hours, before the mice were euthanized. Autopsies were performed, and tumors, testis, and en bloc prostate, bladder and Seminal vesicle were removed, weighed, fixed in 10% neutral buffered formalin and embedded in paraffin for Histological analysis,
Fixed tissues were sectioned and immunostaining procedures were performed as recommended by the manufacturer to evaluate the proliferative rate using the in situ cell proliferation kit, POD± and the apoptotic rate within the tissues was determined according to the TUNEL assay. Slides were examined by light microscopy at 200X magnification. For each tumor, seminal vesicle, prostate and testis 10 different fields were counted, but those containing necrotic tissue were not counted. Apoptotic bodies were defined by positive staining in the assay and the characteristic morphology of the apoptotic nucleus. The number of bromodeoxyuridine positive cells per high power field was counted. Results were expressed as the mean number of positive cells per high power field. Statistical analyses were performed with commercial software, and apoptotic cell and proliferation counts were compared using Student's test (independent variable or ANOVA.
Patients. From September 1986 to June 1999, 69 patients with biopsy proved prostate cancer were treated with the herb mixture PC-SPES. The patients were completely evaluated and disease was staged before inclusion in the study, and were carefully advised about the possible effects of the drug especially venous thrombosis. They received capsules of 320 mg. PC-SPES orally 3 times a day. The patients have been followed periodically through complete clinical evaluation with physical examination, radiological, studies when necessary, and prostate specific antigen (PSA) measurements at 2 and 6 months initially, and every 6 months thereafter. The known side effects of nipple tenderness, gy-necomastia, hot flashes, erectile dysfunction and thromboembolic events were evaluated.

RESULTS
Apoptosis induction in prostate cancer cell fines. Cultured prostate cancer cell lines (LNCaP. PC3 and DU145) were individually exposed to 4 or 6 Ul/mI. of an ethanol extract of PC-SPES for 5 days. Controls received normal medium or medium supplemented with 4 or 6 ul/ml. 70% ethanol alone. At the end of 5 days apoptosis was measured on the cells by the TUNEL assay that immunohistochemically detects cells with fragmented DNA in the nucleus, typical of apoptosis- No statistical differences were observed between the control groups (0, 4 or 6 (ul./ml. 70% ethanol) of any individual cell type (data not shown). Figure 1 demonstrates that PC-SPES extract had significant effects in inducing apoptosia in all cell
Tumor xenografts. We evaluated the effects of PC-SPES in vivo using the hormone insensitive prostate cancer cell line PC3 injected subeutaneously in immunodeficient nude mice. During the study all mice were weighed weekly, and. mean weights of each experimental group were statistically similar to those of controle (data not shown)- Tumor volumes were estimated after 1 month and twice a week during a 1-month followup (fie. 2). Tumors weights at autopsy correlated well with the last tumor measurements (fig. 3). PC-SPES did not suppress tumor growth when therapy was initiated at 1 week after tumor injection (ANOVA p = 0.75). However, smaller tumors were observed in the treated (group 2) compared with the nontreated (group 1) group when PC-SPES therapy was started the same day as tumor cell! injection, although the difference did not reach statistical significance (931 ± 89 versus 1,424 ± 685 mm.3 ANOVA p = 0.23). Testis and en bloc prostate, bladder and seminal vesicle were removed and weighed- A statistical difference was observed between mice receiving PC-SPES, which had smaller testis and en bloc prostate, bladder and seminal vesicle weights, and control mice (fig. 4).
Results of immunostaining for apoptotic bodies using the TUNEL assay and the tumor cell proliferation index are presented in table 1 and figure 5, No difference was observed for the apoptotic rate or the proliferation index between the untreated (group 1) and treated (group 2) groups. However, the apoptotic rate was significantly higher in prostates of the treated mice versus the control mice ((table 1).
Cllnical study of PC-SPES in patients with prostate cancer. Patients; A total of 69 patients were included in our prospective study (table 2). We divided these patients into 3 different groups based on whether they had received prior therapy for prostate cancer and whether they were experiencing relapse. Group A included 43 prostate cancer patients who had received prior cryotherapy, radiation therapy, hormone therapy and/or radical prostatectomy, group B 22 who had received prior hormonal therapy and were experiencing recurrence and group C 4 with localized, untreated prostate cancer who received PC-SPES as primary therapy. Clinical and Biochemical Progression: At a mean followup of 8,5 months (range 1 to 26) none of the patients had overt clinical signs of disease progression, such as increased bone pain.local recurrence presenting as urinary obstruction, or positive bone scans. Using changes in serum PSA as a marker of biochemical response or progression of disease, we evaluated objective responses to PC-SPES therapy (decreased serum PSA) in the patient cohort. Overall, 82% of patients had decreased serum PSA after 2 months of therapy, and at each followup more than two-thirds had a lower level of PSA compared to pre-PC-SPES therapy serum PSA. This ratio was observed in each patient group (table 3). Interestingly a large proportion of patients (74% at 6 months) with hormone refractory prostate cancer had decreased PSA levels at different followup times. Of the treated patients 9 had metastatic disease of whom 2 were in group B and 7 in group A. At 2-month follow-up all of these patients had decreased serum PSA, which was maintained at 6 months in 87%. At 12-month followup PSA was lower than before PC-SPES therapy in 2 cases. Bone scans were not repeated because the patients had a decreased serum PSA and did not present with bone pain. After exclusion of patients with metastatic disease 63% of our patients had stage T1 (decreased serum PSA in 86%), 14% T2 (decreased PSA to 60%) and 27% T3 decreased PSA in (100%) disease. Side Effects: Overall the treatment was well tolerated. Reported side effects were nipple tenderness in 42% of patients, which did not require treatment interruption, gynecomastia in 88% hot flashes in 7% and deep venous thrombosis in 2% (1 patient who interrupted therapy concomitant with introduction of heparinization) No difference was observed among the 3 patient groups for the frequency of these side effects. Local recurrence presenting as urinary obstruction, or positive bone scans. Using changes in serum PSA as a marker of biochemical response or progression of disease, we evaluated objective responses to PC-SPES therapy (decreased serum PSA) in the patient cohort. Overall, 82% of patients had decreased serum PSA after 2 months of therapy, and at each followup more than two-thirds had a lower level of PSA compared to pre-PC-SPES therapy serum PSA. This ratio was observed in each patient group (table 3). Interestingly a large proportion of patients (74% at 6 months) with hormone refractory prostate cancer had decreased PSA levels at different followup times. Of the treated patients 9 had metastatic disease of whom 2 were in group B and 7 in group A. At 2-month follow-up all of these patients had decreased serum PSA, which was maintained at 6 months in 87%. At 12-month followup PSA was lower than before PC-SPES therapy in 2 cases. Bone scans were not repeated because the patients had a decreased serum PSA and did not present with bone pain. After exclusion of patients with metastatic disease 63% of our patients had stage T1 (decreased serum PSA in 86%), 14% T2 (decreased PSA to 60%) and 27% T3 decreased PSA in (100%) disease. DISCUSSION PC-SPES is a unique phytotherapeutic amalgam that is being used by patients with prostate cancer. In a previous study we showed that an alcoholic extract of PC-SPES has a potent dosage dependent effect of decreasing the growth rate of hormone sensitive (LNCaP) and insensitive (LNCaP-bcl-2, PC3 and DU145) prostate cancer cell lines. However, the growth suppressive effects of PC-SPES appeared to be less effective against the hormone insensitive lines compared with the hormone sensitive LNCaP These data suggest that PC-SPES has the potential for activity against hormone independent prostate cancers while showing that this effect can be at least partially suppressed by apoptotic inhibitory molecules, such as bcl-2, that are known to be expressed in some advanced prostate cancers. Other studies have shown that PC-SPES can inhibit the growth of PC3 and MCF-7 breast tumor cells in cell culture.
In this study we confirmed that PC-SPES can induce apo-ptosis in hormone sensitive (LNCaP) and insensitive (PC3 and DU145) prostate cancer. Hsieh et al demonstrate'd that PC-SPES decreased the production of PSA and the expression of androgen receptors in a culture of LNCaP prostate tumor cells.19 DiPaole et al were unable to determine whether the effects of PC-SPES on cultured tumor cells were independent of estrogenic activity since estrogen alone induces apoptosis in tumor cell lines. PC-SPES has potent Estrogenic activity and contains multiple compounds but not the known estrogens, estrone, estradiol or diethylstilbestrol, or chemicals with similar structures and metabolites. In nude mice xenografts of PC3 cells tumor growth was decreased by PC-SPES but did not reach the level of significance. In our in vivo experiment we observed a decrease in the weights of the combined prostate, seminal vesicle and bladder, and testis of treated mice after 2 months of PC-SPES therapy. There was also an increased apoptotic rate in these sexual accessory tissues in PC-SPES treated versus untreated mice, which would support the Estrogenic effect of PC-SPES. In a clinical trial DiPaola et al studied 8 patients taking PC-SPES and observed decreased testosterone and PSA within 2 to 6 weeks.19 PC-SPES effects have been similar to those of Diethylstilbestrol in terms of PSA decrease and side effects observed. *Some patients (4 in group A and 1 in group B) missed serum PSA valuation at 2 months but had PSA evaluated at 6 months. In our prospective clinical trial wo presented our results in 3 categories according to hormone sensitive status and prior therapy. Of the patients 4 received PC-SPES as primary treatment of disease. The follow-up is short but in most of these patients serum PSA decreased. Also, of 22 patients who' received PC-SPES for hormone refractory prostate cancer, serum PSA decreased in 90% at 2-month follow-up and remained decreased at 6 months in 74%, Finally 48 patients had been treated previously with radiation therapy, cryo. therapy, radical prostatoctomy and/or hormone therapy but were considered to have hormone refractory prostate cancer. Decreased serum PSA was observed In 82% of the 43 patients at 2 months, 78% at 6 months and 82%- at 12 months of follow up. Compared to our previous report in the present study with longer followup and more patients, we confirmed that PC-SPES can decrease serum PSA in more than two-thirds of our patients. Our experience is similar to that reported by others. Mittelman et al reported that at 3 months 10 of 16 patients showed a decrease in PSA in excess of 50%. Kameda et al studied the in vivo affect of PC-SPES in a phase II study in which 34 patients received 9 capsules of PC-SPES daily. Of 20 patients with hormone naive disease 12 and of 14 with androgen independent prostate cancer 12 were available for 1-month followup and PSA decreased greater than 50% in 75% and 70%, respectively. Testosterone level decreased to anorchid levels by 1 month in 33% of the patients. As a result of phyto-estrogenic properties, the risk of potential side effects of PC-SPES are theoretically the same as those seen with diethylstilbestrol especially thromboembolic phenomena, end caution must accompany its use We also observed side effects, such as tender gynecomastia in 43% of patients, hot flashes in 7% and venous thrombosis in 2%, which would be typical of estroggenic therapy. Kameda et al reported that 60% of patients with previously normal testos-terone levels had lost libido and other side effects, including tender gynecomastia in 71% (if grade 1 nausea in 12% and grade 1 diarrhea in 33%. (ref: 21) To date there is no Food and Drug Administration approval for PC-SPES or for any other herbal therapy. In the literature most studies reporting the use of herbal therapies did not randomize the cases. However, as emphasised by Fair, the basis traditional medicine is the practical use of herbs for more than 3,000 years "by intelligent people with a strong history" of interest in healing common diseases.22 CONCLUSIONS The effect of PC-SPES On prostate cancer cell lines as well as its clinical activity is an interesting phenomenon. Based on the results of our study and those reported in the literature, we can confirm an estrogen-like activity of this herbal amalgam on prostate cancer cell lines and prostate cancer. However, Our observation that this agent has a clinical effect on patients with hormone resistant prostate cancer suggests that estrogen-like activity is not its sole mechanism of action.
PC-SPES extract preparations were obtained from Dr. Sophie Chen. New York Medical College, New York. New York. REFERENCES 1. Landia, S. H., Murray, T., Bolden, S. et al; Cancer statistics, 1999.- CA Cancer J Clin. 49; 8, 1999 2. Ross, R. K. and Henderaon. B. E.; Do diet and androgens alter prostate cancer risk via a common etiologic pathway? J Natl Cancer Inst, 86: 252. 1994 3. Nam. R. K , FIeshner, N., Rakovitch, E. et al: Prevalence and patterns of the use of complementary therapies among prostate Cancer patients an epidermological analysts. J Urol, 161;1521, 1999 4. Kellis, J. T,, Jr. and Vickery, L. E.; Inhibition of human estrogen synthetic (aromatase) by flavones. Science, 225, 1082. 1984 5. Agarwal, K., Wang. Z. Y, and Mukhtar, H.; Inhibition of mouse skill tumor-initiating activity of DMBA by chronic oral. feeiling of glycyrrhizin in drinking water. Nutr Cancer, 15s 187, 1991 6. Smith, R., E,, Donachie. A M. and Mowat, A. M.: Immune stimulating compIexes as mucosal vaccines. Immunol Cell Biol. 76;268,1998 7. Wang, S- Y., Hsu, M. L., Hsu, H. 0. et al: The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Cancer, 70: 688,1997 8. Matsuzaki, Y.. Kurokawa, N., Terai. S, et al: Cell death induced by baicalein in human hepatocellular carcinoma cell lines. Jpn J Cancer Res, 87; 170. 1998 9. Ghosh, J. and Myers, C. E.: Inhlbition of arachidonate -lipoyygenese triggers massive apoptosis in human prostate cancer cells, Proc Natl Acad Sci U S A, 95; 131.82. 1898 10. Kyo. R, Nakahata, N., Sakakibara I. et al Effects of Shosoiko-to, San'o-shashin-to and Scutellariae Radix on intracellular Ca2+ mobilization in. C6 rat glioma cells. Biol Pharm Bull, 21;1067, 1998 11. Kubo, I.: Structural basis for bitterness based on Rabdosis Deterpenes, Phygiol Behav, 56; 1203, 1994 12. Nagao, Y., Ito, N., Kohno, T, et al; Antitumor activity of Rabdosia and Teuctium diterpenoids against P 388 lymphocytic leukemia in mice- Chem Pharm Bull (Tokyo), 30: 727, 1982 13. Wilt, T. J.. Ishani, A., Stark, G.- et ah Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. JAMA. 280; 1604.1999 14 de la Taille, A., Hayek, 0. R,. Buttyan, R. et al Effects of a phytothorapeutio agent, PC-SPES, on prostate cancer: a preliminary investigation on human cell lines and patients. BJU Int, 84; 845, 1999 15. Kubota, T., Hisatake, J,, IIisatake. Y- et al: PC-SPES: a unique inhibitor of proliferation of prostate cancer cells in vitro and in vivo Prostate, 42; 163,2000 16. Tiwari, R. K., Geliebter, J., Garikapaty, V. P- et al: Anti-tumor effects of PC-SPES, an herbal formulation in prostate cancer. Int. J Oncol, 14: 713. 1999 17. Halicka, H. D,. Ardelt, B., Juen, G. et al: Apoptosis and cell cycle effects induced by extracts of the chinese herbal preparation PC-SPES Int J Oncol, 11; 487. 1997 18. ft. Hsieh, T.. Chen. S. S:, Wang, X. et al; Regulation of androgen receptor (AR) and prostate specific antigen (PSA) suppresion in the androgen-responsive human prostate LNCaP cells by ethanolic extracts of the Chinese herbal preparation PC-SPES. Biochem Mol Biol Int. 42; 535,1997 19. DiPaola, R. S., Zhang, H., Lambert, G. H, et al: Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. N Engl J Med, 889: 785,1998 20. Mittelman, A., Tiwari, R. K. Chen, S. et al: Preclinical analysis of the in vivo and in vitro effects of PC-SPES on rat prostate cancer cells. J Clin Oncol, vol. 18, 1999 21. Kamada, H,, Small, E. J., Reese. D. M, et al: A phase II study of PC-SPES, an herbal compound, for the treatment of advanced prostate cancer (PCa). J din Oncol, vol 18, 1999 22. Fair, W_ R.: Back to the future-the role of complementary medicine in urology. J Urol. 162; 411,1999 EDITORIAL COMMENT Complementary and alternative medicine is used by .more than 40% of patients in the United States, and urology patients are no exception.1 Patients seek complementary and alternative medicine for a variety of reasons including failure or traditional therapy, avoidance of side effects, desire for a more natural approach to healing and desire to maintain control over therapy Thus, it is not surprising that men with prostate cancer have sought out such an approach because hormonal therapy fails with time, has multiple and protean side effects if prescribed and administered by physicians, and often leads to poly pharmacy. Into this environment moves PC-SPES, & combination of 1 American and 7 Chinese herbs. This study and others demonstrate un-equivocally that this amalgam has activity in prostate cancer. and clinically causes a decrease in PSA, In this study PSA decreased greater than 50% in two-thirds of the patients with hormone naive and hormone refractory disease. In the authors' previous report of 33 patients 87% had a decrease in PSA (reference 14 in article) and in another small series of 8 patients all exhibited a decrease in PSA (reference 19 in article}. Finally in a recent sorties of 34 patients with hormone naive and hormone refractory disease 75% of patients in both groups had a PSA decrease of greater than 50% (Reference 21 in article), The authors have forthered our knowledge regarding this agent, and demonstrated that significant apoptosis is soon in PC3, DU145 and LNCaP cell cultures, of which 2 cell lines are hormone insensitive, Nevertheless in the PC3 xonograft no significant difference in tumor volumes or proliferation rates was noted. Of interest was a lower apoptosis rate in the prostate and a significant proliferation rate in the testis. The cause for these changes remains unknown, in the mixed population of men with prostate cancer responses in PSA Were the rule with about three quarters exhibiting a PSA decrease of greater than 50%, which is a threshold often used to declare significant activity of antincoplastic agents. Most intriguing was the observation that the degree of response appeared to be similar in hormone naive and hormone resistant disease. The results of this study, especially the clinical results, should prompt more interest in PC-SPES, However I am disturbed by several observfations. The mechanism action of the agent remains unknown, and the specific component(s) of the agent that cause this effect remains unknown. Also the appropriate dose is unknown, and the side effects are significant despite the lack of regulation of the use of the agent. It is of interest that in a previous study by the authors of patients who were treated in what appears to be a similar protocol (I presume that the current study is a longer followup with a large number of patients but includes the original 33) DVT developed in 2 of 88 (Reference 14 in article). In the present study only 1 of 69 patients had deep venous thrombosis. Breast tenderness with PC-SPES has now been reported in 6% to 100% of patients (references 14 and 19 in article). The sterols in this agent, although dissimilar to estrone. estradiol and Diethylstilbestrol are nevertheless estrogens and can be expected to cause other cardiovascular side effects (reference 19 in article), Without large scale, detailed, clinical trials we will not know if the degree of cardiovascular mortality is Iess than or greater than that previously wen with diethylstilbestrol.1 The findings of this report are exciting and disturbing. We have evidence that some or all of the compounds in this mixture have an effect on hormone refractory prostate cancer that may be highly significant. The prospect of lives saved in an otherwise incurable disease is an electrifying development It comes at a risk, however, of a serious side effect. If this agent undergone appropiate testing by a pharmaceutial manufacturer we would know an appropriate dose, have a tailored combination of agents and have detailed information regarding side effects and methods to possibly prevent them. Because of the lack of regulation of agents such as these, physicians and patients must take the place of the agency that provides oversight for regulated pharmaceuticals. Cardiovascular and thrombo-embolic deaths attributable to this agent can be expected as its popularity grows. Could deaths be averted through appropriate oversight? Could a better agent have been designed if each component had been appropriately tested? With the significant cost of the agent, which is $162 to $486 a month. and Since it is not on traditional formularics, one must question whether patients arc being denied a potentially effective treatment. In the current environment we may never know. The efficacy and toxicity of PC-SPES should be a call to action for elected officials to demand testing of agents, such as these, that by any other definition are truly pharmaceuticals We cannot allow less for our patients. Ian. M. Thompson Jr. Division of Urology The University of Texas Health Science Center at San Antonio San Antonio, Texas

PC-Spes Kills Cancer Cells, Stimulates Immune System. Evidence builds for herbal treatment against prostate cancer
PC-SPES and Prostasol can be ordered at Medpro - Scherpenzeel - Netherlands Address: Medpro Holland B.V. Dorpsstraat 182 3925 KG Scherpenzeel Phone: +31 33 2867642 Fax: +31 33 2867647 Email product information: information@med-pro.org Email office: office@medpro.org 30th. of october 2001: Source: WebMD Medical News Evidence Builds for Herbal Treatment Against Prostate Cancer
PC-SPES Kills Cancer Cells, Stimulates Immune System By Michael Smith , MD WebMD Medical News Oct. 30, 2001 -- Evidence continues to mount in support of the herbal combination treatment PC-SPES for prostate cancer. This brawny botanical appears to kill cancer cells while at the same time stimulating the body's own immune system to help fight the cancer. "PC-SPES means hope for prostate cancer," says Sophie Chen, PhD, who presented an update of the latest findings of PC-SPES at a meeting of the American Medical Association. "In fact, PC-SPES is delivering more than hope to prostate cancer patients," she says in a news release. PC-SPES is a combination of eight herbs. Chen says that in the laboratory, each herb has been shown to have cancer-killing ability while stimulating the immune system to fight the cancer as well. The power of all the herbs working together makes this a strong cancer treatment, she says. This botanical appears to work best in certain types of men with prostate cancer -- men whose tumors grow in response to male hormones, such as testosterone. She reviewed findings of four separate studies looking at the use of PC-SPES in 178 men. Among the 98 men whose tumors were sensitive to hormones -- determined after a biopsy -- 80% of these men had their PSA cut in half, an indication that the tumor was responding to the treatment. In contrast, just 52% of the men whose tumors did not grow in response to hormones had the same benefit. The men who responded to the treatment also had improvement in prostate ultrasounds and in bone scans, which detect prostate cancer that has spread to the bones. Another study of 137 men showed that after treatment with PC-SPES for six months to four years, 93% of the men had either lowering or stabilization of their PSA, an indication that the cancer had stopped growing. These men also rated their quality of life as quite high -- 71% as seven or higher on a scale from one to 10, and 20% even rated themselves a 10. PC-SPES research is looking very promising, but it doesn't come without side effects, some of which can be serious. PC-SPES can act like the female hormone estrogen, which helps it fight prostate cancer. However, this also causes most of the side effects, such as breast enlargement and tenderness and reduced sexual libido. It can also cause diarrhea and muscle cramps. Blood clots are the most worrisome side effect, but occur in less than 5% of men. Chen recommends that PC-SPES be taken under a doctor's supervision to monitor side effects and to check the cancer's response to treatment. "In my opinion, chemotherapy alone cannot attain the goal of remission because it can only control the cancer in the short term. Therapy combined with herbal compounds seems to be effective because it provides the one-three punch of killing cancer cells and modulating the [hormones] while boosting the immune system," Chen says. Chen is a shareholder and co-founder of International Medical Research, Inc. in Brea, Calif., the manufacturer and distributor of PC-SPES.

Cryoablation Superior to Brachytherapy for prostate cancerpatients, due to large randomised trial
29th. of may 2001: Source: Endocare Endocare Reports New Data Shows Cryosurgery Produces 92 Percent Disease Free Rates as Primary Treatment for Prostate Cancer. 7-Year Data to be Published in Journal Urology Shows Cryoablation Superior to Brachytherapy; Study Shows Significant Improvement in Post-Procedure Potency Over Time With No Radiation Risk IRVINE, Calif., May 29 /PRNewswire-FirstCall/ -- Endocare Inc. (Nasdaq: ENDO), a developer of innovative diagnostic and treatment tools for cancer and other diseases, announced today that seven-year follow-up data from a peer-reviewed, retrospective study demonstrated that cryoablation as a first-line treatment for prostate cancer can be equally or more effective than brachytherapy, without the potentially toxic side affects of radioactive seeds. The 590-patient study, to be published in the upcoming edition of the journal Urology and presented by clinical researchers at a Company-sponsored forum held in conjunction with the American Urological Association (AUA) annual meeting in Orlando, showed disease-free survival rates for low, medium and high risk patients were 92 percent, 89 percent and 89 percent respectively, as measured using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. These results compare favorably with existing survival data associated with other treatment modalities such as brachytherapy, especially in medium- to high-risk patients. In an additional study to be published in the same Urology article, three-year prospective data measuring patients' quality of life before targeted cryoablation as well as at regular intervals after the procedure showed for the first time that sexual function often returns after cryoablation. The data demonstrated that 47 percent of men who were sexually active before the procedure ultimately resumed having intercourse within the three year period -- a trend comparable to the reported 50 percent of men that undergo brachytherapy whose sexual function returns over time. Daniel B. Rukstalis, M.D., Head of the Division of Urology, MCP Hahnemann University School of Medicine and Guest Editor of the special Urology issue, said that improving cryosurgical techniques are leading to improved outcomes -- both in terms of successfully treating the disease and in controlling morbidity -- and are compelling the urology community to rethink its primary treatment option for prostate cancer. "What may have been considered a novel medical technology a decade ago has today come into its own as a powerful tool against cancer," Rukstalis said. "This new long-term survival data on targeted cryoablation, combined with its minimally invasive nature and its low morbidity rates, indicate its growing importance as a primary therapy. In addition, it is a procedure that can be easily repeated in those few instances where the cancer may reoccur, unlike radiation." Paul Mikus, President and CEO of Endocare, said the new clinical data continues to validate cryosurgery as a viable, and many times preferable, option for the treatment of prostate. "This seven-year data validates the claims of the pioneering physicians who adopted this technology during the past decade," Mikus said. "Today, men have a minimally invasive option that has been shown clinically superior in treating their disease -- involving no radiation and fewer side affects. I expect the number of men seeking out this approach will grow, as will the number of physicians who have considered the data and wish to offer their patients a choice." About Targeted Cryoablation
While radical prostatectomy has historically been the "gold standard" for treatment of prostate cancer, many men are considering less-invasive treatment options that involve faster recovery, less severe side effects and fewer complications. Targeted cryosurgery is a minimally invasive procedure that involves no radiation or open surgery and only one percent of patients report incontinence. During targeted cryosurgery, a patient is first treated with epidural anesthesia; he is awake and can talk to the physician, but feels no pain during the procedure. The physician inserts slender cryoprobes through a small incision into the prostate gland. Liquefied argon gas, which is contained within the cryoprobe tips, freezes the cancerous tissue reaching -- 40 degrees Celsius (- 40 degrees Fahrenheit). After approximately 10 minutes, the physician completes the first freeze cycle and then immediately administers another treatment to help ensure that all cancer cells are killed. The entire procedure lasts about one to two hours and the patient can return home that day or the next morning. In general, patients can resume a normal lifestyle immediately after the procedure. Some patients may experience mild soreness for two to three days following targeted cryosurgery; however, this side effect is common among all surgical prostate cancer treatments. Long-term side effects of targeted cryosurgery are similar to other therapies and may include impotence, bladder outlet obstruction, pelvic pain, chronic urgency and rectal injury. CHICAGO (Reuters Health) Nov 28 - Focused cryosurgery for ablation of a single prostate lesion is a safe alternative to nerve-sparing prostatectomy, with little to no effect on sexual potency, according to study findings presented at the 87th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA). Dr. Gary M. Onik, director of surgical imaging at the Center for Surgical Advancement, Florida Hospital Celebration Health, Celebration, Florida, explained that because cryosurgery "causes no trauma at all to the nerve," the procedure can preserve potency "even when we remove one nerve, because the remaining nerve is untouched, fine." He said that nerves and other anatomy, including the rectum, are spared because "we manipulate the lesion by injecting saline into the surrounding tissue before freezing. This effectively creates wider margins." Dr. Onik reported results from a series of nine patients. The men were all high-risk patients with a prostate-specific antigen of more than 10, a Gleason score of at least 7 and/or T2 lesions. The age range was 55 to 70. "Seven of the nine men have retained full potency," Dr. Onik reported. Moreover, the procedure was done on an outpatient basis and the men were able to return to work in 5 days. "That compares with weeks of recovery after surgery, including possibly 6 weeks of daily radiation," Dr. Onik said. "All of the patients have stable PSA, and six of the men have had negative biopsies," Dr. Onik said. There was no incontinence associated with the procedure. While two men did not retain potency, cryosurgery was "a successful cancer treatment for them," he said. In one man, the first patient in the series, "both nerves were frozen. We didn't intend to do that, but we were still learning," said Dr. Onik. The other man had a number of comorbidities, including a previous prostate surgery that contributed to impotence. Dr. Onik told Reuters Health that the procedure is much less costly than surgery, and "cryosurgery is already FDA-approved, so this option is available right now." Although high-risk patients were enrolled in the series, Dr. Onik said the greatest potential for focused cryosurgery is "for men who are in that middle group, the watchful waiting patients. Why not offer them a treatment rather than waiting for the cancer to progress?"

The Influence of Finasteride - Proscar on the Development of Prostate Cancer
24th. of june 2003: Source: New England Journal of Medicin. Published at www.nejm.orgg June 24, 2003 (10.1056/NEJMoa030660)
The Influence of Finasteride on the Development of Prostate Cancer. Ian M. Thompson, M.D., Phyllis J. Goodman, M.S., Catherine M. Tangen, Dr.P.H., M. Scott Lucia, M.D., Gary J. Miller, M.D., Ph.D., Leslie G. Ford, M.D., Michael M. Lieber, M.D., R. Duane Cespedes, M.D., James N. Atkins, M.D., Scott M. Lippman, M.D., Susie M. Carlin, B.A., Anne Ryan, R.N., Connie M. Szczepanek, R.N., B.S.N., John J. Crowley, Ph.D., and Charles A. Coltman, Jr., M.D. Background Androgens are involved in the development of prostate cancer. Finasteride, an inhibitor of 5-reductase, inhibits the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate, and may reduce the risk of prostate cancer.
Methods: In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men 55 years of age or older with a normal digital rectal examination and a prostate-specific antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal. It was anticipated that 60 percent of participants would have prostate cancer diagnosed during the study or would undergo biopsy at the end of the study. The primary end point was the prevalence of prostate cancer during the seven years of the study. Results:
Prostate cancer was detected in 803 of the 4368 men in the finasteride group who had data for the final analysis (18.4 percent) and 1147 of the 4692 men in the placebo group who had such data (24.4 percent), for a 24.8 percent reduction in prevalence over the seven-year period (95 percent confidence interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors [37.0 percent], or 6.4 percent of the 4368 men included in the final analysis) than in the placebo group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005 for the comparison between groups). Sexual side effects were more common in finasteride-treated men, whereas urinary symptoms were more common in men receiving placebo. Conclusions Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer. Notice: This article was published at www.nejm.org on June 24, 2003, to coincide with the National Cancer Institute's announcement of the early termination of this trial. The article will appear in the July 17 issue of the Journal. Mixed Results for Drug Used to Prevent Prostate Cancer June 25, 2003 By MARY DUENWALD A drug that doctors had hoped might prevent prostate cancer has been found to be both more effective and potentially more dangerous than expected. After giving a daily dose of the drug, finasteride, sold by Merck under the brand name Proscar, to more than 4,300 healthy older men for seven years, researchers found that the men's chances of getting prostate cancer were 25 percent lower than for those of a like-size group of men who took placebos, according to a report released online yesterday by The New England Journal of Medicine. But 280 of the men who took finasteride, or 6.4 percent, ended up with especially aggressive cases of prostatecancer, compared with 237 in the placebo group, or 5.1 percent. Whether or not a man should take finasteride to prevent prostate cancer is "an individual decision for a man and his physician," said Dr. Charles A. Coltman Jr., chairman of the Southwest Oncology Group in San Antonio and a leader of the nationwide study. Men who stand a particularly high risk of developing prostate cancer - blacks and men with close relatives who have had the disease - might consider taking the drug as a preventive measure, Dr. Coltman said. In the study, the drug proved to be as protective for high-risk men as it was for others. But Dr. Peter T. Scardino, head of urology at Memorial Sloan-Kettering Cancer Center, in New York City, who wrote an editorial about the study for the Journal, said most men should not take finasteride, because the possibility of developing a more aggressive form of cancer appeared to be too great. "The 25 percent reduction in cancers is quite impressive, and I think this study opened an enormous area of research," Dr. Scardino said. "But when doctors look at this carefully, I don't think they're going to prescribe Proscar to people to prevent prostate cancer." Dr. Coltman said the National Cancer Institute ended the 10-year study 15 months early, not because it concluded that finasteride was dangerous but because the results had already conclusively demonstrated the drug's mixed effects. "More information wouldn't have changed the outcome," he said. The men who took finasteride experienced a greater number
of sexual problems, including reduced libido and erectile dysfunction. Finasteride, which keeps testosterone from converting into a more active form, has been used since 1992 to treat benign prostatic hyperplasia, or enlarged prostate, a condition unrelated to prostate cancer. The drug shrinks the prostate and makes it easier to urinate. Men who are now taking the drug to treat the condition are safe to continue doing so, Dr. Scardino said, as long as their doctors monitor them for signs of cancer, with bloodtests and digital rectal examinations. "I wouldn't want to scare people who are already taking Proscar into stopping," he said. "I've been telling my patients, if you're on Proscar, we'll just keep an eye on things a little closer." The same drug, sold under the brand name Propecia and administered in one-fifth the standard dose, is used to treat baldness. Men can safely continue taking Propecia, too, as long as they are careful to be checked for prostate cancer, Dr. Scardino said, noting that most men who take this drug are under 55. Although the researchers do not know why the finasteride group ended up with more high-grade cancers, they speculate that the drug might clear the way for the growth of tumors that are less dependent on testosterone, and that such tumors can be more aggressive. "By changing the hormonal environment within the cell, finasteride appears to promote the selective growth of high-grade cancers," said Dr. Joseph A. Smith Jr., head of urologic surgery at Vanderbilt University Medical Center, in Nashville, and an investigator in the study. Another possibility is that by lowering levels of prostate-specific antigen, or P.S.A., and causing the prostate gland to shrink, finasteride may cause men to have normal-seeming P.S.A. tests and digital rectal exams and thus allow any emerging cancers to grow to a more aggressive stage before they are discovered, Dr. Scardino said. Then again, the drug may not be to blame at all. "We need more research to determine the reasons for the increase in the number of high-grade cancers," Dr. Smith said. Prostate cancer is the second most common form of cancer, after skin cancer. An estimated 220,900 cases will be diagnosed in the United States this year, according to the American Cancer Society, and 28,900 men will die of the disease. Doctors have traditionally focused on diagnosing and treating the disease early, and have only recently turned their attention to finding ways to prevent it.
Another national trial is looking into the possibility that vitamin E and the mineral selenium may reduce the risk of prostate cancer. Results from this study are not expected for several years.

Tomato Consumption - Lycopene - Can Lower Prostate Cancer Risk
- Tomato Consumption Can Lower Prostate Cancer Risk - WASHINGTON (AP)--A diet rich in tomato sauce, ketchup and other tomato-based products containing a powerful antioxidant can lower the risk of prostate cancer, a new study says. Researchers analyzed the food choices and prostate cancer histories of more than 47,000 men and found that those who ate at least two meals a week containing tomato products lowered their risk of prostate cancer by 24-36%. Dr. Edward Giovannucci of Brigham and Women's Hospital and the Harvard School of Public Health, the first author of the study, said it supports earlier research involving foods, particularly tomato products, that were high in lycopene, a powerful antioxidant. "These most recent finding add support to the notion that a diet rich in tomatoes and lycopene-containing foods, as well as other fruits and vegetables, may reduce the risk of prostate cancer," said Giovannucci. A report on the study appears Wednesday in the Journal of the National Cancer Institute. Giovannucci said that lycopene is thought to protect against cancer by absorbing oxygen-free radicals, which are chemicals created during metabolism that can damage the genetic structure of cells. The finding is based on data from the Health Professional Follow-Up Study, a project that followed the health history and dietary habits of 47,000 men, aged 40 to 75, from 1986 to 1998. During that period, 2,481 of the men developed prostate cancer. Dietary questionnaires in the study included such food items as tomatoes, tomato sauce, tomato juice, pizza, watermelon and pink grapefruit, along with salsa, ketchup and other tomato-based condiments. When the data was adjusted for the effects of other life style factors, the researchers found that tomatoes, particularly those that had been cooked, were beneficial against prostate cancer.

Low-Fat Diet May Reverse Prostate Cancer due to study from Prof. MD. Dean Ornish
-- WSJ(4/11) Low-Fat Diet May Reverse Prostate Cancer -- By Thomas M. Burton and Laura Johannes A study of dietary changes in prostate-cancer patients suggests that low-fat eating, coupled with lifestyle changes, can stop or reverse the progression of the disease in its early stages. The research was headed by Dean Ornish, the University of California-San Francisco medical professor best known for low-fat diets in treating heart disease. While the study was small, the results were intriguing. Researchers followed 84 men with cancers that were relatively unaggressive and hadn't spread beyond the prostate. All had already opted for "watchful waiting" instead of surgery or radiation. Half were randomly selected to be put into a program with the low-fat diet, aerobic exercise and stress management. At three months and after one year, the low-fat diet group had lower PSA, or prostate specific antigen, a blood marker associated with regression of the disease. The other group had higher levels of the blood marker, suggesting disease progression. Peter R. Carroll, chairman of urology at UCSF, who collaborated with Dr. Ornish on the research, stressed that the findings may not be applicable to men with advanced or very aggressive cancers. But the results appear important, as more than 30,000 Americans die annually of prostate cancer and aggressive treatment like surgery often means unpleasant side effects. "Not all prostate cancer needs to be treated aggressively, and small low-grade cancers can be handled well with surveillance and lifestyle changes," Dr. Carroll said. Separately, a study on prostate surgery published in today's New England Journal of Medicine said that men who had their prostates removed by surgeons who perform at least 16 prostatectomies annually suffered fewer complications than patients whose surgeons performed fewer than four a year. The study suggests that patients considering surgery for prostate cancer should not be afraid to ask their doctors how many operations a year they perform, said E. Darracott Vaughan Jr., president of the American Urological Association. However, Colin C. Begg, the study's author, cautioned, "We found a very wide variation even among high-volume surgeons." The Ornish dietary study doesn't prove that a low-fat diet will lengthen lives, though a higher and fast-rising PSA does suggest a more lethal cancer. Dr. Ornish said he hopes to continue his work to evaluate the question of longer lives, as well as whether his approach can avoid cancer recurrence. But the yearlong work already showed that none of the 40 low-fat-diet patients needed surgery or radiation, which often cause impotence and incontinence. By contrast, seven of 43 patients in the control group did have such procedures. The findings are expected to be presented Saturday at Harvard University at the Scientific Conference on Complementary, Alternative and Integrative Medical Therapies. Charles E. Myers Jr., a urologist in Charlottesville, Va., and former director of the University of Virginia's cancer center, said the research "doesn't address survival, but it shows a dramatic effect." Moreover, in his view, the low-fat diet approach will work for prevention of prostate cancer, as well. "I think the evidence that it would be useful for prevention is clear." The dietary study is consistent with previous scientific evidence. Last year, doctors at the University of California-San Diego, the University of South Carolina and elsewhere had already found that a plant-based diet combined with stress reduction could slow prostate tumor progression. But that work didn't include the essential step of randomly assigning patients to a control group, to compare the effects of the diet. The findings on surgery strengthen the growing body of evidence that, in medicine, practice makes perfect. Over the years, many studies have found mortality after major surgical procedures is lower at larger, high-volume medical centers. The research published today is unusual in that it focuses not on mortality, but on complications from surgery. "Since the mortality is so low in prostate cancer, what really matters is the outcome for the patient and the patient's quality of life," said Dr. Begg, a researcher at Memorial Sloan-Kettering Cancer Center in New York. The researchers examined medical records from 11,000 men who had surgery between 1992 and 1996 and counted major complications in the month after surgery, such as bleeding or heart attacks. They also cataloged trouble urinating or incontinence, which can occur months or years later. The researchers didn't study impotence because this side effect is often not recorded in computerized medical records, Dr. Begg said. The scientists found that both surgeon volume and hospital volume made a significant difference in the outcomes. In a group of "high volume" surgeons, defined as those performing 16 to 58 prostatectomies annually, 26% of patients had postoperative complications such as bleeding, heart attacks or kidney trouble. In a group of "very low volume" surgeons, defined as those performing four or fewer prostatectomies a year, 32% of patients had these complications. Within a year of surgery, 28% of patients operated on by very low-volume surgeons experienced trouble urinating, compared with only 20% of the very-high volume surgeons' patients.