P A A C T, I N C. CANCER COMMUNICATION P COMM UNI CATI ON NEW SLETTER • VOLUM E 2 2, NUM BER 2 • Sep t em b er 2 00 6 FOUNDER: LLOYD J. NEY, SR. – FOUNDED 1984

President and Chairperson: WHAT THE HECK HAS BEEN GOING ON IN MY WORLD- Janet E. Ney PART 12!!! By Mark A. Moyad, M.D., M.P.H.

Board of Directors: PISTONS DO NOT RULE! That is all I need to say about that - by the time Edwin Kuberski you read this article I will have finished professional mental therapy for the Treasurer second year in a row because the Pistons blew it in the playoffs. Well, there is always the Michigan football season in a few months (time to restart therapy). Newton Dilley Helen Mellema 71) I heard you are on ABC radio every Saturday from 11AM to Noon! Peter Noor Jr. Richard H. Profit Jr. Was I drinking a lot of pomegranate juice that day or are you really on Anthony Staicer this show? The show is called “The Doctor is in” with Dr. Mark Moyad and Stephen Stewart. If you go to WJR.com on Saturday mornings at 11AM to Noon East- Honorary Board Member: ern Standard time you can listen to the show live anywhere in the world on your computer. In the Midwest the radio dial is 760 AM and it is the same sta- Russell Osbun tion my father listened to when I was a kid (neat stuff)! It is a 1-hour general prevention and show and I have no idea how long it will last. We have already talked about sunscreen, weight loss, exercise, … I was only sup- Medical Advisory Board: posed to be a guest for one show and we are now on our sixth show. Feel free to go to WJR.com and email them and say nice things about me, or if you Richard J. Ablin, Ph.D. V. Elayne Arterbery, M.D. have nothing nice to say, feel free to say something bad about anyone else but Robert A. Badalament, M.D. me. You can email them and ask how to get copies of the old shows... I hope Duke K. Bahn, M.D. you all get a chance to listen because we are having a lot of fun (understate- Israel Barken, M.D. ment of the year). E. Roy Berger, M.D. Michael J. Dattoli, M.D. Fernand Labrie, M.D. 72) There is a new vaccine (Zostavax®) for the prevention of Shingles. Fred Lee Sr. M.D. No, this is not prostate cancer information, but for the past 103 years (or has it Robert Leibowitz, M.D. only been 102 years) of writing for PAACT you probably realize that I am Mark Moyad, M.D., M.P.H. somewhat a fan of preventive medicine. On May 26, 2006 the FDA approved Charles E. Myers Jr. M.D. Zostavax® made by Merck, which is the first vaccine ever approved for the Gary M. Onik, M.D. Haakon Ragde, M.D. prevention of Shingles. The ideal candidates for this vaccine are men and Oliver Sartor, M.D. women age 60 years or older that have never had a bout of shingles. What is Stephen B. Strum, M.D., FACP shingles? It is a reactivation of the old chicken pox virus and it can be quite Donald Trump, M.D. painful and debilitating. It is possible that other Steven J. Tucker, M.D. Ronald E. Wheeler, M.D. Let’s Conquer Cancer in OUR Lifetime younger individuals and some individuals that have in one area of cancer but may have activity in another had shingles in the past may qualify for this injection area of cancer. In addition, by the time you read this but as more research comes from the clinical trials we newsletter we should have a good idea of whether or will get a better idea. In the meantime, if you are in- not the pill “Xinlay” by Abbott has a chance of get- terested in this vaccine please talk to your primary ting FDA approved anytime soon for hormone refrac- care doctor. My job was just to let you know it has tory prostate cancer (HRPC), so talk to your doctor been approved because I was really excited about it. about this also. It seemed to reduce the risk of getting shingles by about 50% over several years, and even if you did get 74) What is Metabolic Syndrome (MS) and why is shingles it seemed to lessen the severity of the dis- it important to prostate cancer patients? ease. This injection is simple and is only given as a (Reference: Abstract 4554 from the American Society of Clinical On- cology Meeting 2006. Flanagan JR, et al-Indianapolis VA Study. single or one time injection. Also, it is about 14 Metabolic Syndrome patients on predicts for a shorter times the concentration of the chicken pox vaccine, response time.) that is why an entirely different vaccine was needed. There are several different definitions of metabolic syndrome, but basically having at least 3 of the fol- 73) I heard there are 2 new drugs approved for lowing factors increases the risk of type-2 diabetes advanced kidney cancer that you can take as a pill and cardiovascular disease (CVD). The overall five and they are now testing these drugs in advanced factors are: prostate cancer. What are the names of these -High blood pressure drugs? -Low HDL or “good cholesterol” The name of the first drug is “Nexavar®” or so- -Abdominal obesity (waist circumference of 40 inch- rafenib tosylate from Bayer, and the name of the sec- es or more) ond drug is “Sutent®” or sunitinib malate from Pfiz- -High triglycerides (from the cholesterol blood test) er. These are exciting times and it could be that the -High glucose or sugar level next breakthrough for prostate cancer comes from kidney or colon cancer research or another cancer. If A very good and interesting study was presented at your situation is more desperate please talk to your our annual oncology meeting in Atlanta this year. doctor about some of these drugs that are already The researchers looked back in time at patients on approved INDEX Page 1. What The Heck Has Been Going On In My World CANCER COMMUNICATON – Part 12! (Mark A. Moyad, MD, MPH) Published Quarterly by: PAACT, Inc. Patient Advocates for Advanced Cancer Treatments 6. Should I or Shouldn’t I Join a ? (Is- 1143 Parmelee NW Grand Rapids, MI 49504 rael Barken, MD)

Director…Richard Profit 11. New Molecular Tests Can Predict the Return of Editors….Richard Profit/Molly Meyers Prostate Cancer (Jason Alter, PhD) Assistant….Molly Meyers Webmaster….Art Schlefstein 12. Steven Tucker, MD Takes a Sabbatical Postmaster: Send address changes to: Prostate Cancer Communication 13. GoodSearch P.O. Box 141695 Grand Rapids, MI 49514 13. High Dose Replacement Therapy & Prostate Cancer - Part 1(Robert Leibowitz, MD) Phone: 616/453-1477 Fax: 616/453-1846 E-Mail: [email protected] 18. Brad Guess Memorial PAACT Web Page: http://www.paactusa.org Newsletter: http://www.paactusa.org 19. CA Regional Prostate Cancer Conference 2006 Editor: 19. Prostate Cancer Risk Linked to DNA Articles authored by other than the editor may not fully reflect the views of the corporation but are printed with the 20. International Conference on Prostate Cancer 2006 understanding that the patient has the right to make his own interpretation of the efficacy of the information provided. In an effort to conserve space and be able to insert as 21. Ask Dr. Barken much material as possible in the newsletter, references from various articles are intentionally omitted. If you would like to obtain those 21. Acknowledgements references, please contact PAACT, we keep all of the original articles and the references used on file. 23. Financial Summary suppression for prostate cancer and found flow rate (an objective measure completed by the that men with metabolic syndrome had a shorter re- physician). There were also a number of secondary sponse time to the drug and a greater risk for early outcomes including: change in the prostate size, urine death. In other words, having metabolic syndrome or volume left in the bladder after urinating, quality of some of the above characteristics of metabolic syn- life, laboratory values and side effects. Let’s look at drome had the potential to make a prostate cancer some of the characteristics of these men at the begin- prognosis worse! Here is another reason to begin to ning of the study in this table. exercise, lose weight, and improve cholesterol, blood pressure and your sugar levels after a man has been Table. Characteristics of the participants at the begin- diagnosed or treated for prostate cancer. ning of the saw palmetto versus placebo study Approximate Saw palmetto Placebo 75) Saw palmetto was safe at 320 mg per day, but characteristics of Group Group it did not work any better than a placebo for mod- the 225 partici- (112 patients) (113 patients) erate-to-severe benign prostatic hyperplasia pants (BPH) after 1 year of use. (Reference: Bent S, Kane C, Shinohara K, et al: Saw palmetto for be- Average age 63 years 63 years nign prostatic hyperplasia (BPH). N Engl J Med 354: 557-566, 2006.) Percentage of 16% 21% This was simply a wonderful clinical trial, and the re- non-white or mi- searchers and patients in this study should be com- norities mended for being a part of one of the best herbal Average AUASI 15.5 15 studies in medical history (in my opinion)! Saw pal- Score metto enjoys a tremendous amount of sales around (scores run 0-35 the world. Some areas of Europe have made this with 0-7=normal, herbal product a prescription, but in the U.S. there are 8-19=moderate, literally hundreds of over the counter (OTC) brands. and 20-35=severe Florida and several coastal states are some of the BPH) largest exporters of this herbal product. This herbal Prostate volume 34.5 ml 34 ml product is so well known that it continues to be one Maximal urinary 11.5 ml/sec 11.5 ml/sec of the more popular supplements taken by men to flow rate prevent prostate cancer. However, this is the scary Residual urine or 80 ml 84.5 ml part, saw palmetto has never had any credible data amount left in that it reduces the risk of prostate cancer. All of the bladder after uri- preliminary data is for the improvement of BPH nating symptoms. Some researchers suggest it has a finas- PSA 1.8 1.6 teride (a drug approved for BPH) type effect, but un- like (also known as Proscar®) it has not When the trial ended after one year of treatment there been shown to have any impact on PSA levels. Re- was no difference between saw palmetto and placebo gardless, there was an urgent need to conduct a gov- in all the major areas of the study including no differ- ernment funded and non-industry supported clinical ence in quality of life, PSA, or side effects. Several trial to determine if saw palmetto really does any- criticisms or what I like to call “Monday morning thing. Now, researchers can say that this trial was not quarterbacks” have raised several questions about only funded but was recently completed and pub- this study, but let me answer them one by one to lished. This study was funded by the National Insti- demonstrate just how well this trial was done. tute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the National Center for Comple- -Why didn’t the researchers use a higher dose of saw mentary and Alternative Medicine (NCCAM). palmetto? They used 320 mg/day because this was by far the A total of 225 men with moderate-to-severe BPH most common dosage used in the past clinical trials symptoms were randomized to saw palmetto extract that demonstrated a consistent benefit. at a dosage of 160 mg twice a day (320 mg a day to- tal) or placebo. The primary outcomes being studied -Why didn’t they use a more popular brand of saw were the change in score on the American Urological palmetto for the study? Association Symptom Index (AUASI, a subjective The researchers attempted to do this, in my opinion, measure completed by patients) and the maximal but some companies did not want to be a part of this trial. They ended up using a product from Rexall- -How effective is placebo for BPH? Does this trial Sundown (“Indena”), but this product went through give any indication? rigorous testing to make sure it fit all the standards. You bet! What did not seem to receive attention from Also, I believe more people should give Rexall-Sun- this trial was the fact that all of the potential partici- down credit for volunteering their product when it pants in this trial were first placed in a 1-month, sin- seems they had little to gain and a lot to lose finan- gle-blind, placebo run-in phase and were not allowed cially by participating in this trial. In my opinion, in the trial unless they took 75% or more of the place- this is a saw palmetto product that should be recom- bo. In other words, in order to really determine who mended potentially for those with mild BPH, because was committed to going through this entire trial, the at least now it is known that is safe. participants had to take placebo pills for 1-month pri- or to the start of the study, which lasted for 12 months -What kind of standards did the saw palmetto product on saw palmetto or placebo. It is absolutely fascinat- adhere to in this trial? ing that there was actually a significant despite small Many of the popular alternative medicine consumer improvement (or decrease) in the AUASI during this books have espoused for years the use of a saw pal- 1-month period! This goes to show the placebo effect metto with either 80-95% combination of fatty acids that occurs with BPH and it has to be accounted for, and sterols or 85-95% fatty acids and greater than and the researchers wisely accounted for this issue. 0.2% sterols. The herbal extract used in this trial demonstrated a consistent 90-92% fatty acids and -Were men on prescription drugs for BPH allowed to 0.33% sterols, which means it was right on target or be a part of this trial? even above the standards of what has been recom- Men were not allowed to be on a prescription drug mended in the past for effectiveness. The placebo for BPH during this trial. If they stopped taking a even had an odor similar to saw palmetto so that the prescription “alpha-blocker” at least 1 month before patients could not tell them apart. The placebo con- the trial or a prescription “5-alpha-reductase in- tained polyethylene glycol-400, which is a bitter-tast- hibitor” at least 6 months before the trial, then they ing liquid with an oil makeup. It contained no free were allowed to participate. Men with a greater risk fatty acids, and a brown coloring agent was used in of complete urinary blockage or urinary retention order to ensure no difference in appearance between (defined as a urinary flow rate of less than 4 ml per saw palmetto and placebo. second or urine amount of 250 ml left in bladder after urinating) were not allowed in the trial because this is -Why wasn’t the study done in men with mild BPH a type of BPH too severe to be treated by medication. symptoms and larger ? Other types of men not eligible for the trial included Perhaps studying men with more mild BPH symp- men with: a history of prostate cancer, surgery for toms and not those with moderate-to-severe BPH BPH, serious urethra or bladder conditions, high cre- would have been a better study, and perhaps men atinine levels, PSA level greater than 4.0 ng/dl, those with larger prostates would have also been a better on medications that impact urinary flow or those in- group. The reason for this is due to the suggestion dividuals with a serious disease of any type. that saw palmetto works similar to a drug that shrinks larger prostate glands. However, again in defense of -Was there a difference in any of the side effects be- the researchers in this trial, studying only mild BPH tween saw palmetto and placebo? would have been filled with problems such as a large There was no difference, and in fact no side effect placebo effect, and the encouragement of medicating was reported at a significantly higher rate than place- a condition that for many men needs no medication at bo. Perhaps this might also explain why saw palmet- certain points. Regardless, when the researchers to had no effect, because there may not have been looked at the men with more or less symptoms than enough active ingredients or it may not work any bet- the average or with smaller or larger prostate glands ter than placebo anyway. I get nervous whenever a there was still no difference between saw palmetto pill or any medical intervention has a side effect pro- and placebo. In the future one could study only men file identical to placebo because I am concerned that with mild BPH, but the dosage of saw palmetto might it really does not have an impact any better than the have to be higher, and a large number of patients sugar pill. Personally, I like to see some side effects would be needed at a very large cost in order to deter- at a low rate and some efficacy. Only 10 men in the mine if the product is working better than a placebo. saw palmetto group (5 lost to follow-up and 5 stopped the medication because of other issues), and 9 in the placebo group (4 lost to follow-up and 5 and treated with this cancer because of the lack of in- stopped the medication) did not complete the entire formation in this area. I have always been fascinated study, which means a drop-out rate of less than 10%, by the fatty acids in saw palmetto, and one of them is which is excellent for a clinical trial. oleic acid, which is a similar fatty acid found in some healthy foods like olive oil. Perhaps saw palmetto -Why was the trial only 1 year long, and not 2 years has some anti-inflammatory properties, but this has for example? yet to be proven. This trial was one of the longest saw palmetto trials in the history of medicine. The majority of the past Bottom Line trials were about 12 weeks or shorter. BPH trials of 1 Saw palmetto extract at 320 mg per day with meals year or more are more than adequate to determine if a worked no better than placebo in reducing the symp- medication is working. The researchers could have toms of BPH in men with moderate-to-severe dis- done this trial over 6 months, but in my opinion 1- ease. Higher dosages will be tested to see if they year was the perfect amount of time to determine if have any effect. In the meantime, prescription drugs saw palmetto was better than placebo. In fact, pa- work well for most men with this condition. Men tients had 8 clinic visits during the trial, which was with mild BPH may want to take this product, espe- also more than enough to determine the impact of cially due to the low cost, but again this should be up saw palmetto. to the patient and the doctor. However, the saw pal- metto used in this study (Rexall-Sundown, Indena -Okay, so what is next for saw palmetto? Should U.S.A.) should be discussed as a possibility because men use this herbal product ever again? at least it is now known that it is safe. We have no Approximately 2.5 million men in the U.S. use saw idea what happens if you take saw palmetto for the palmetto, and it is one of the top ten selling herbal prevention or treatment of prostate cancer because it supplements in the U.S. and around the world. Per- has never been adequately studied. Regardless, some mixon®, a saw palmetto product from France, is one men tend to take it for “prostate health,” which of the most studied saw palmetto products in the makes me nervous. world, but they were not a part of this trial and men cannot buy this product in the U.S. Regardless, it 76) supplements (pills) in low or high seems to have an identical make-up to the product dosages did not seem to do anything for men with used in this trial. Also, a very large herbal trial called a rising PSA after surgery or radiation treatment. “CAMUS” was going to be done but it has since been Reference: Clark PE, et al. Urology 67:1257-1261, 2006. changed because of the results of this trial. Instead, This was an interesting, unique, and somewhat disap- the next trial will involve dose escalation, which pointing study. A total of 36 men with a rising PSA means higher dosages of saw palmetto will be tested, after localized therapy (24 had radiation and 12 had and the herbal product pygeum africanum may also surgery) were included in this study. A total of 6 be tested. It could be that saw palmetto works better groups of 6 men each were told to take different at a higher daily dosage or not at all and this will be dosages of daily lycopene supplements for 1 year. tested soon. The dosages of lycopene were 15, 30, 45, 60, 90, and 120 mg (6 different dosages for the 6 different Saw palmetto is very cheap compared to prescription groups). PSA and blood levels of lycopene were drugs for BPH so I believe some men will continue to measured every 3 months. The average age of the use it regardless of the results just because of price. patients was 74 years, but the youngest patient in the In fact, some men may want to try it for mild symp- study was 56 years old and the oldest was 83 years toms and if it does not help, they should use a pre- old. The average PSA level was around 4.4 ng/ml. scription or have a procedure done. The bottom line There were no PSA responses in any of the patients is that the prescription drugs work so well for most during the year of the study. A PSA response was de- men that they should be given more credit. Whether fined as a 50% decline in PSA from the beginning of or not saw palmetto extract should be tried by pa- the study. A total of 13 patients (37%) actually expe- tients at all; this should be determined by the patient rienced PSA progression during the study. PSA dou- and the doctor, but at least this trial sheds some light bling times and other parameters did not change for on the 320 mg per day dosage for men with moder- the patients during the study. There were no signifi- ate-to-severe BPH. Again, it should not be taken for cant side effects of the lycopene pills except for one the prevention of prostate cancer or men diagnosed case of diarrhea. The blood levels of lycopene in- creased during the first 3 months to similar levels for ONSHIP - heck this year I am not expecting much the dosages of 15 to 90 mg a day, but the 120 mg except a 40 point win over Notre Dame, Ohio dosage increased blood levels to the highest level of State, and Penn State). all, but then began to decrease during the end of the study. Finally, Mark I heard you are the new editor of a medical journal by Elsevier called “Seminars in Pre- The lycopene pill used in this study (Lyc-O-Mato®) ventive and Alternative Medicine” and it is going to was one of the most popular pills used in past studies go online in September and will include regular med- which seemed to indicate that lycopene might have ical updates. Is this true? Yes it is and if you go to some effectiveness for prostate cancer patients. The the web-site of Elsevier publications (www.elsevier.- compliance rate was 100%, or in other words these com or call 1-800-654-2452) you can order the same men were highly motivated and took their pills daily medical journal that the health professionals can use throughout the year. The blood levels of lycopene that updates the latest on diet, supplements, and also indicated that this supplement was absorbed well drugs… for cardiac disease, different cancers, and by the body. However, there was just no indication anything else that is happening in preventive and al- of a clinical response during the study in any patient. ternative medicine. This is the end of this shameless What does this mean? Should I stop eating tomatoes promotion, but seriously, for some patients the medi- or using lycopene pills? What this simply means is cal journal should be a good source of objective edu- that it does not seem that taking high-dose lycopene cation. THAT IS ALL - GO BLUE! pills for a rising PSA after surgery or radiation has any dramatic effects. Personally, I would save your Should I or Shouldn’t I Join a Clinical Trial? money. However, this does not mean that lycopene By Israel Barken, M.D. from a diversity of foods (tomato products, watermel- Prostate Cancer Research and Education Foundation on….) have no impact or are not healthy. The food www.pcref.org sources are at least heart healthy so you are still the 619-461-8181 winner in this case. The lycopene pill is controversial because it seems to have some impact for advanced In recent years, there have been changes in how a pa- patients, but not in localized patients. The truth of tient enters a clinical trial. As I travel around the the matter is that researchers are not sure whether or country, I hear researchers invite patients to join their not lycopene pills have any definitive effect at any studies, flashing their web site address (Experiment.- stage of prostate cancer. Some groups will probably com) and urging the audience to call the researchers argue that this study did not use a placebo group, so directly on their 800 number. The media also does a we could not know for certain whether or not ly- zealous job of reporting so called "breakthroughs." copene pills really had an impact. However, this They loudly sound the herald of each new discovery dosage range study was well done and some response in the war on cancer. If only the happily cured mice should have been seen if the pills are effective. It could speak and give exclusive interviews of their ex- could be that these pills work better for preventing periences. Prestigious academic institutions fill Sun- the disease than treating the disease, or it could be day's newspaper with big ads advertising studies to that the pills are worthless. The bottom line is that join. Between the public speeches, the media hype they seem to be safe, and if you decide to take them it and the advertisements of academia, one could easily is a complete “guinea pig approach” as we say in the be convinced that a cure is at hand and you - yes, business. Personally, I would wait for more research YOU could be one of the first to receive this amazing and get this healthy compound from food. Save your new miracle drug. "Step right up, ladies and gentle- extra money for the time being and buy me a gift on men, step right up." my birthday, which is February 15. Media hype has created a romantic aura around cer- HAVE A NICE DAY, AND MAY YOUR UPCOM- tain buzz-words like “vaccine,” “gene therapy” and ING FALL BE FILLED WITH EXERCISE, “immune therapy.” And God bless our researchers HEALTHY & SOME UNHEALTHY FOODS, who want to help humanity by finding better treat- AND VISIONS OF MICHIGAN FOOTBALL ments that will someday benefit us all. But the pa- BRINGING HOME THE NATIONAL CHAMPI- tient about to enter a trial is not concerned with hu- ONSHIP THIS YEAR TO WHERE IT BELONGS manity, and his agenda is more immediate than some- (OR AT LEAST THE BIG TEN CHAMPI- day. His outlook is individual, his timeframe is right now. Each patient should ask the hard questions one. He can articulate his philosophy about quality about whether a particular clinical trial is good for of life issues. He has an understanding of how much him or not. Who can help educate patients to under- risk he is willing to accept to gain a certain benefit. stand what it means to enter a trial study? What tools Remember too, that the decision to join a study is can we give them to evaluate that trial before they only one part of the process. In my experience, an- sign on the dotted line? other vital question is, “Who will make the decision to drop out of the study?” and again, the patient's in- This article is written for the patient who is about to put needs to be foremost. say, "I'm ready to join a study." Some patients reach this stage because they have exhausted all other av- The clinician ("the Coach") is supposed to be that enues of treatment. They are dying, and they have doctor who knows the patient and his family best. In nothing to risk. Therefore, any gain, a month or even these days of managed care, that is not always a valid two, is a benefit. This article is not written for them. assumption because patients change groups frequent- This article is written for patients who have time, ly and doctors come and go rapidly. Be that as it who have choices, who have standard treatments they may, the main problem facing the clinician is that he have not yet tried, and who want to make the best does not have the same first hand knowledge of the possible decision about whether they should join a clinical trial as the researcher. Some clinicians en- clinical trial. This article will explain who should courage patient referrals when they feel that they can join a study, how to make the decision, where to seek not handle the situation, and the patient needs expert competent advice, when is the best time to join a advice from somebody in academia. If your doctor is study, how to pick a study, and most important, when transferring you to a clinical trial for these reasons, to drop out of a study. you need to look hard for a more skilled coach. The patient needs a coach who will work with him, even I believe that the best person to turn to when you con- when he is having a bad season, and not transfer him template joining a clinical trial is your own doctor, to another team to be rid of him. the person I like to call your "Coach." It is a com- mon belief that if you join a clinical trial, you have to The researcher usually is someone who serves in an leave your doctor. I disagree. You're in a new game, academic institution. His productivity, his title, and but every player needs a coach who is familiar with his prestige are measured by how many papers he his strengths and weaknesses to guide him through produces and publishes. Patient care obligations are the plays. The coach is a professional in the game, shared with doctors in training at the academic insti- knows the player, and has guided other players before tute. How many of his publications are accepted in you. I feel strongly that if you are going to enter a prestigious medical journals is the standard by which clinical trial, don't go alone. Make the decision to- his worth and his rise in the academic ranks is mea- gether with your doctor (your Coach) because he will sured. His goal is a broad and noble one: to save hu- be an invaluable asset to you. manity by finding a cure for cancer or to improve the lot of humanity with bold, new treatments. He is in- Entering a clinical trial is indeed a big decision to terested in enrolling the patient in his clinical trial to make and there are three distinct participants in the study and quantify human reactions to the new treat- decision making process: the patient and his family, ment. The researcher has no dilemma about putting the physician who regularly takes care of the patient some patients in a placebo group while others get the (the Coach), and the researcher conducting the study. new drug, since this comes to serve science and to serve humanity. Whether it serves a particular indi- Let's describe each participant, examine their vantage vidual is not necessarily the researcher's primary point, and see how they influence the final decision. goal. It is telling that when a patient enters a trial, he The patient and his family usually do not have the trades his name for a set of initials and numerals. depth of knowledge about the overall disease that the You may argue that the researchers are protecting the professionals do. Many patients have educated them- identity of their subjects, but by the same token, they selves very highly about prostate cancer, but they are are erasing that identity too. not professionals. Sometimes, the patient has initiat- ed the search for a clinical trial, but more often it is How can the patient evaluate a proposed clinical tri- the recommendation of the clinician or the researcher. al? Before he looks at the specifics of that trial, he The patient, however, knows himself better than any- first needs to make a basic calculation. What is the benefit and the risk of this clinical study to me versus group that did not get any efficient treatment at all. the benefit and risk of accepting a standard treatment As a matter of fact, only 4% of participants in Phase I available in my own community? There is a tenden- trials get any benefit at all. That is a fact to consider cy to believe that everything new is better, even with your doctor before entering a Phase I study. miraculous, that every discovery is a step forward. But remember, at least in medicine, not everything In Phase II, the attention is shifted from safety to effi- which is new is good. By the same token, not every- cacy. (Note, however, that only about 70% of studies thing old is bad either. make it from Phase I to Phase II.) The questions to be answered in Phase II are: The patient needs to approach joining a study in the 1. Is the tumor shrinking? most egotistic manner. The most important question 2. Are the tumor markers regressing? is why should I join this study? What's in it for me? The dose has been determined in Phase I. Now, the A little background about the nature of clinical stud- highest safe dose is given to 14 patients. If none of ies is helpful here in understanding where the clinical these patients respond, the drug is considered worth- trial you are about to enter has its roots. There are less. If one patient responds then a total of 30 pa- some parts to the process before a trial enters human tients are treated. One of the advantages of this phase work. First, the search for new treatments starts in is that usually there is no randomization of the pa- the laboratory where the idea of a drug is tried in test tients. tubes or glass plates. A tumor is grown in culture in glass and the drug is tried there. This is called an "in Phase III (Note that only about 33% of all trials enter vitro" study. If there is success in this stage, the re- Phase III investigation, 67% are discarded after Phase search goes on to the next phase, which is trying the I or II): In this phase the new treatment is compared treatment on animals. Two factors are tested on the to the standard treatment. Phase III is initiated only animals: the efficacy of the drug and the safety of the after the treatment has shown some promise in Phas- drug. It is absolutely critical for the reader to under- es I and II. Phase III includes large number of pa- stand this one point: what works in test tubes or on tients in multi-centers. Patients are randomized, animals may not work at all on humans. Therefore, meaning the individual does not have control over I believe that it is important for the patient to have a which group he is assigned to, nor does he have con- disclosure of the initial basic research results and to trol over what kind of treatment he receives. If you consult your doctor ("your Coach") to help you un- are contemplating whether to join a study because derstand these results. you absolutely want to receive a specific treatment, beware of joining a Phase III randomized clinical tri- Let’s move on to discuss the different phases of clini- al. cal studies. The human studies are divided into 4 identifiable phases: Phase IV: In this study a known proven medication approved by the FDA from a previous study is being In Phase I, the questions to be answered are: checked for a different indication or different dose 1. How should the medication be administered? setting. Data is collected and compared to estab- (Oral , Injection, Infusion) lished treatments. 2. What is the best dose? 3. What are the side effects? Compassionate studies provide a “wild card”: Pa- tients with very advanced disease and no available It is standard practice in Phase I to recruit a small treatments can receive a drug not yet approved or yet number of patients, usually three patients at each available on the market. Under “compassionate dose level. The dose is raised until either the patient use,” the drug can be given on an individual basis. gets sick or the desired result is achieved. Once that For example, was originally made avail- level is achieved, six or more patients are then treated able to individual patients who had run out of possi- with the same level to make sure it is a safe dose. The ble treatments through a special arrangement with the main question here is: How safe is the drug and at FDA. Another example: Under compassionate use, what dose? The highest dose that can be tolerated is Casodex was originally approved to be given to pa- the focus of the experiment in Phase I. This means tients who suffered from severe diarrhea on Eulexin. that it is possible that the patient will be part of a Eventually the drug Casodex was approved by the started on a lower dose in Phase I and by the time FDA. you get an increased dose (if the study even provides for increased dosing), a few months may go by with- In summary, only 30% of Phase III studies are sub- out being treated. This may be dangerous ground for mitted to the FDA for approval. Of these, only 20% some patients to tread. Here is where you and your are indeed approved by the FDA. It takes a company coach need to carefully assess the risk versus benefit 2-10 years to complete the studies on Phases I, II, and ratio. If you are already on shaky ground medically, III. It may take the FDA 3-20 years to approve the fi- what can happen if you stop all treatment for a month nal product. What does this mean for the patient? It or more? If you receive a promising new drug, but means that the majority of studies in which patients the dosage is too small to be effective, where will you participate are not found to have any real benefit. be three months from now? Ask your doctor to help Joining a study in a more advanced phase minimizes you sort out all of the possible scenarios before you the risk to the patient and maximizes the potential of make your decision to join a clinical trial. being safe and effective. 4.You will receive a document called “Informed Con- In looking at an individual clinical trial, here's what sent” which is going to explain the study and your you need to know: rights as a patient. You will be asked to sign this doc- 1.Each study is carried out according to a strict action ument so take the time to study it, ask questions of plan. This action plan is known as the "protocol." the researchers, and understand it thoroughly before The protocol explains what is done during the period signing. of the study. Each study has to be approved by an "Institutional Review Board" or IRB. The IRB is a 5.One of the most important questions to think about committee of health professionals, members of the before you enter a clinical trial is when to drop out of community like clergymen, lawyers and patient advo- the study. As any good card player will tell you, you cates. They are responsible for the study being ap- have to "know when to hold 'em, know when to fold propriate and avoiding unethical risks. As a patient 'em. Know when to walk away, know when to run." about to enter a clinical trial, you have to know who The decision to drop out of a study is very common, is sponsoring the study and what organization is be- yet rarely addressed beforehand. In making the deci- hind it. sion to drop out, the criteria of the researchers may not fit your needs as a patient. In many Prostate 2.Selection criteria for studies is a key element in the Cancer studies there is a decision to take the patient clinical trial. This is described in the protocol. The off the study when the PSA rises by more than 50% eligibility criteria are important for the researchers. in two measurements over a period of 2-3 months. They will seek to create groups of similar patients. You may be pressured to obey by this rule. The inter- You may not qualify under their criteria. Before trav- est of the researcher is to keep you in the study so he eling to an institution for the purpose of joining a can have a meaningful paper for publication. You study, have your doctor (your Coach) make the ini- may feel obliged to follow the rules. Keep in mind tial connection with the researchers and make sure however, that your primary responsibility is to your- you qualify. Two main areas for refusing patients to a self, to preserve your life, and not the good for hu- study are: manity as represented by the researchers. A. Patient must have good organ function. These include liver function, kidney func- What are the possible benefits you can derive from tion, adequate number and function of joining a study? There are many. blood components. 1.You may receive treatment in a center of excellence B. Prior treatment which will make evalua- and have a very tightly controlled environment in tion of the study difficult. which you can follow your disease through many tests that otherwise would not have been done. 3.You should know what phase the study is in. If you 2.If the treatment in the study is working, you may be have other proven options still available to you, there one of the first ones to enjoy a good result. This is is no sense in joining a Phase I study. Remember that especially true with the more advanced phase studies. in most studies you will be asked to stop all medica- 3.You may have the cost of your care covered by tions prior to joining. That means that for a whole funds provided for the study. month or more you will not be treated. You may be 4.By being part of the study you may feel good by 8.Are there any “early stopping rules?” Is treatment doing something altruistic for society. going to be stopped if too many patients experience significant side effects or if the treatment is found to There are also some possible drawbacks to be aware be less effective than expected? of when joining a study. They are: 9.What are the expected benefits from both a short 1.New treatments under study are not always better term and long term point of view? than standard treatments. 10. What are the expected side effects? 2.You may suffer from side effects that even the re- 11. How will your daily life be affected? searchers did not suspect. 12. What are the competing standard treatments for 3.You do not have any control over which arm of the which you qualify, and how do they compare? study you are assigned to. Neither does your refer- 13. How often will you have to be seen and for how ring physician. You may get a placebo in certain in- long? What is the follow up for the study? stances. 14. Where will the study take place? Will you have 4.You may incur some costs for your medical care to be hospitalized? Will it be done on an outpatient that will not be covered by your insurance so be alert basis? and check the financial rules of the study very care- 15. What kind of support is available to you and your fully. family while you are in the study? 16. How will you know if the treatment is working or What are your rights as a patient contemplating join- not? How often is it going to be evaluated? ing a study? 17. Will you be able to see your own doctor? 1.You and only you have the right to choose a study 18. Who will be in charge of your care? versus standard existing treatments. It is wise to in- volve your own doctor (your Coach) in this decision. "Should I join a Clinical Trial?" is the title of this ar- 2.You have the right to leave the study at any time ticle. I hope you have found some food for thought without any need to give any explanation. before taking the leap. If you were about to buy a 3.You have a right to have your privacy protected. used car, most of you would take it to a trusted me- 4.You must be given an Informed Consent document chanic or perhaps drive to a professional diagnostic to read and sign. All the facts of the study should be station to get an evaluation before you buy. Your given to you. This should include explanations about body is serious business too and unlike a car, you the treatment, tests, risks, benefits and financial cov- only get one model per lifetime. I urge you to seek erage. out the advice of your doctor, your trusted "Coach" 5.Any new information while you are in the study and let him help you sort out the right reasons for should be given to you. You have the right to ask the joining a specific study. Your doctor can help you doctors how the study is going with other patients differentiate between a good study and a "walk on the and you should get honest answers. wild side." In talking about any specific trial with you and your family, your doctor will help you weigh Finally, I would like to offer you a list of practical the risk versus the benefit. If you are into "wishful questions to ask before joining a study: thinking" about a glamorous study, he will point out some of the realities and help you avoid pitfalls. Af- 1.What phase is the study in and what is the study de- ter all, there’s no need to donate your body to science signed to prove? while you’re still using it, right? Taking into account 2.What is the scientific information prior to this study the whole picture of where you stand in your treat- that makes it worthwhile? ment options and the history and course of your dis- 3.Who reviewed the study and approved it? ease so far, your doctor can help you evaluate 4.Who is sponsoring the study? Which drug compa- whether you need to join a study at this juncture. He ny is behind the study? Are the researchers at liberty may point out other treatments that you still have to publish their results or is this to be decided by a available to try before you volunteer for an experi- drug company? ment. As in every phase of surviving prostate cancer, 5.How is my privacy going to be protected? please don’t go it alone. Talk to your Coach, use his 6.Can you be given names of patients that are in the input, and play to win. study? 7.What are the safety features of the study and who is New Molecular Tests Can Predict checking? the Return of Prostate Cancer Jason M. Alter, Ph.D. of the patient developing a PSA recurrence within Aureon Laboratories, Inc. five years of having their prostate removed. 914-377-4036 Disease Progression Px Score describes the likeli- Earlier this year Aureon Laboratories released Prostate hood of the patient developing Disease Progres- Px™, the first in a series of tests that predict prostate sion defined as bone/soft tissue metastasis and/or cancer recurrence. The test stratifies patients into high androgen independent rise in PSA within five or low-risk categories for the likelihood of experienc- years of having their prostate removed. ing a return of their prostate cancer after they have had their prostate surgically removed (prostatectomy). Compared to existing methods, Prostate Px provides a very accurate prediction of PSA recurrence with a sen- Approximately 15-40% of patients who have had their sitivity of 96%. In addition, Prostate Px can predict prostate removed will develop a serum PSA or bio- disease progression and does so with a sensitivity of chemical recurrence (BCR). Moreover, a man with 89%. prostate cancer who has had a PSA recurrence can still Prostate Px benefits patients and physicians at a num- develop a metastasis some eight years post PSA/BCR ber of decision points after surgery. The predictive test suggesting that identifying this group of patients early can: in their treatment program is critical to their overall survival. Provide a probability of whether a patient, after a prostatectomy, will have a PSA recurrence within The current practice for following patients after a five years. prostatectomy is to test their blood for prostate specific Predict whether a patient, after a prostatectomy, antigen (PSA) to determine whether their cancer is re- turning. This period can be a time of great anxiety and will have disease progression within five years. many patients are searching for additional sources of Avoid possible side effects associated with therapy information in order to make a more-informed deci- (e.g. androgen deprivation therapy) for asymp- sion about possible treatment options. tomatic low-risk patients. Identify patients with high-risk of clinical failure An accurate prognosis is important because the major- who may benefit from increased surveillance or ity of tumors are indolent and require minimal inter- early adjuvant therapy. vention while a subset are more aggressive and early Help relieve anxiety and allow patients, their fami- intervention may be valuable. As seen in the accompa- lies and their physicians to decide upon the best nying images, it is difficult for the pathologist to deter- treatment regimen moving forward. mine what will happen to the patient by pure visual in- Assist in patient selection for new therapies as part spection of the prostate cancer tumor. Both images are of randomized clinical trials. diagnosed as Gleason score six (6) by standard, exist- ing pathological techniques. One case represents an in- Technology dolent tumor while the other is life threatening. The basis for the predictive power of Prostate Px is its unique breakthrough technology. Aureon’s System Pathology platform combines histological, molecular and clinical information to predict cancer recurrence.

After prostatectomy, the physician orders Prostate Px and a small section of the prostate tissue sample is col- lected from the pathology department at the hospital where the surgery was performed and sent to Aureon’s specialized laboratory. Aureon’s approach integrates: Case #1 Case #2 Indolent Disease Life Threatening Histology (tissue): Prostate Px analyzes the cells The Prostate Px test has two endpoints for cancer re- and other structures in a prostate cancer tissue sam- currence: ple. This results in the generation of specific (quantitative) features for inclusion in the mathe- matical model. PSA Recurrence Px Score describes the likelihood Molecular markers: Prostate Px selectively mea- & Research Institute in Los Angeles, California. I sures specific proteins in prostate tissue samples in will be temporarily moving to Singapore to pursue order to obtain a unique molecular picture of the prostate cancer research projects across Southeast patient’s prostate cancer. Asia. I am available in Los Angeles through August Clinical data: Prostate Px takes into account impor- 2006 and will be available to see patients in Singa- tant clinical information such as the Gleason score pore by mid September. and the pathology results from the patient’s surgery. Additionally, I am excited to announce that Dr. Tonya Dorff from the University of Southern California will By combining these sources of information and by ap- be joining The Angeles Clinic and specifically the plying advanced computer technology and mathemat- Prostate Cancer Program to provide ongoing care for ics, Prostate Px is able to provide patients a more thor- existing patients. Together with Dr. Dorff and ad- ough picture of their individual risk for recurrent dis- vanced communications (email & video conferenc- ease. ing) I anticipate no major changes in the way my practice is handled. Next Generation Prostate Px is just the first in a new generation of pre- For patients outside of the United States or for U.S. dictive tests from Aureon that combines the power of patients willing to travel, I will continue to accept advanced mathematics with biology and clinical prac- new consultations and follow-up appointments in tice. Singapore. I expect to maintain my prostate cancer practice while in Singapore for existing patients. The Aureon is in the final stages of development of new office will have the same amenities as my cur- Prostate Px™ +, a new predictive test for prostate rent practice including chemotherapy, advanced cancer that will use biopsy tissue, at the time of diag- imaging (PET/CT and MRI), immunotherapy, and nosis, and Aureon’s system pathology platform to as- laboratory services. In time I will also open a large sess disease severity. number of unique prostate cancer clinical trials.

Prostate Px™ + will enable the assessment of disease Ms. Allena Tay in my Singapore office can assist pa- severity at the time of diagnosis, thus more informa- tients currently. The staff in Singapore can currently tion will be available to the patient and their physician be reached at: prior to the selection or implementation of any thera- pies. The West Clinic Singapore Excellence Cancer Center Aureon Laboratories is dedicated to improving patient One Orchard Boulevard healthcare and advancing medicine by commercializ- 15th & 16th Floor, Camden Medical Centre ing predictive tests for cancer recurrence. Until now, it Singapore 248649 has been very difficult to identify which patients fall Tel: +65 6565 6888 into a high-risk category and which do not. Prostate Px Fax: +65 6565 9988 tests can help relieve anxiety and assist both patients and their physicians in selecting the most appropriate For international email during this transition I can be treatment options. reached at:

More information on Prostate Px and Prostate Px+ is [email protected] located at www.prostatepx.com or can be obtained via email by sending a request to [email protected] Please be patient with the staff in Singapore as they com. handle any specific needs. I appreciate your patience with this exciting transition. I hope this move can help more men from outside of North America to get Steven Tucker, M.D. Takes a Sabbatical high quality oncology care. Many more details are sure to follow, but I wanted you to know right away. Dear Patients, Please feel free to make this information widely known. I am writing to inform you that as of September 1st, 2006, I will be on sabbatical from The Angeles Clinic Sincerely, Steven Tucker, M.D. The more people who use this, the more money will go to PAACT for its continued fight against Prostate GOODSEARCH Cancer.

There is a new and easy way to raise money for High Dose Testosterone Replacement Therapy PAACT and Prostate Cancer just by searching the In- (TRT) and Prostate Cancer (CaP) ternet with GoodSearch.com. Part 1 Robert L Leibowitz, M.D. It’s simple. You use www.GoodSearch.com like any Compassionate Oncology Medical Group other search engine – the site is powered by Yahoo! – 310-229-3555 but each time you do, choosing PAACT as your chari- ty of choice, money is generated for PAACT. Good- In 1941, Huggins and Hodges reported that removing Search has been featured in The New York Times; O, the testicles in men with metastatic prostate cancer The Oprah Magazine; The Wall Street Journal; ABC resulted in a remission for more than 80% of them. News; and Fortune Small Business. Unfortunately remissions only lasted an average of about 18 months. Last year, search engines generated close to $6 billion in revenue from advertisers. With GoodSearch part of Since removing testosterone (T) initially controlled this advertising revenue will now be directed to metastatic CaP, it is most logical to assume that giv- PAACT. GoodSearch.com will donate 50% of adver- ing T to a man with CaP would be like pouring gaso- tising revenue, estimated to be about a penny per line on a fire. This is what 99.9% + of all doctors be- search, to the charities selected by its users. So each lieve. The package inserts for all TRT products state time you use GoodSearch.com and choose PAACT as that “testosterone is contra-indicated for all men with your designated charity, a penny will be set aside for CaP.” This implies that T will markedly stimulate PAACT. A penny may not seem like much, but if 100 CaP cells to grow, spread and hasten death. supporters of PAACT used GoodSearch.com twice a day it would generate $730 a year. Because of space limitations in this PAACT edition, readers are urged to log onto out website www.com- We hope that not only will you use GoodSearch as passionateoncology,org where you will find the com- your main search engine from here on out, but will plete text I have written on Testosterone Replacement also pass this message on to your friends and family. Therapy along with the medical references that sup- port my beliefs, insights and opinions. This paper and all of my papers may be downloaded at no charge from our website, under Publications. I urge everyone to please read the full text on TRT before trying to determine if you could ever consider TRT. I cannot overemphasize that this paper should not be brought to your doctor along with a request for a testos- terone prescription. Testosterone is contraindicated in men with prostate cancer. It has caused the death of some patients (fortunately, no one in my practice); permanent paralysis, increased bone pain, and new metas- tases. I do not recommend use of T for anyone with prostate cancer. Be Happy, Be Well, Live Long and Prosper, Dr. BOB

* None of the above should be construed as medical advice or consultation, and anything discussed in this paper is meant for information only. All medical treatments, consultations, decisions and recommendations can only be made by the patient and his/her treating physician. TRT CASE REPORTS

1. John H 11/03 – 61 years old; PSA 3346; PAP 82.6; gl 4+4/8 @ John’s Hopkins Hosp (JHH); 7/9 cores; multiple bone mets – 22 lb weight loss 12/03 – 13 months – THB® KC later EE 15 doses – T/E/C thru 4/04 9/04 – PSA 0.003; AAC agents added as tolerated 9/04 thru 1/05 – AAC and THB® 1/17/05 – Stop HB; continue AAC and start TRT 3/05 6/05 7/05 8/4/05 8/18/05 11/05 12/05 1/06 4/06 T 1612 1640 3703 3831 5488 3546 1644 1873 2255 PSA 0.128 0.163 0.372 0.453 0.454 0.360 0.420 0.360 0.330

5/06 6/06 7/06 T 4036 2324 1247 PSA 0.380 0.628 0.501

2/1/06 – Bone scan @ St. John’s Hosp, Santa Monica, CA, compared to 8/18/05, showed there is interval improvement.

2. Stuart B 12/95 – 52 years old; gl 3+3/6 at JHH; 3/6 cores; PSA 7.3 1/96 – 5 mos. L plus 1C then 9 mos. THB® IC 4/97 – 3 mos. THB® 6F per day; Then P alone 9/97 to 10/02 – PSA less than 5; T 500 12/02 – PSA 7.65 7/03 – TRT started; PSA 4.44; T 661

9/03 11/03 1/04 3/04 5/04 7/04 9/04 11/04 1/05 (note 1) T 1498 1545 1539 2062 1043 3678 1540 2674 1214 PSA 8.11 5.7 7.1 5.6 8.35 7.32 8.66 8.59 7

3/05 4/05 6/05 8/05 11/05 12/05 1/06 2/06 3/06 (note 2) (note 3) T 1286 2237 1232 2068 1427 1474 2212 3181 2791 PSA 7.12 6.4 7.57 9.19 9.01 11.1 11.5 9.25 6.92

4/06 5/06 6/06 T 2059 1599 1863 PSA 7.8 7.62 6.99

Notes: (1) Thalidomide 50 mg/noc added (2) GM-CSF added (3) Thalidomide Stopped; Revlimid 5mg/d started

Expired 6/06 of ASCYD; no evidence of CaP cells in prostate, bones or anywhere else in the final autopsy report from the coroner. 3. Russell S 1/92 – 49 years old; PSA 26.3; gl 4+4/8; DRE C; L given 3/92 – R.P. @ JHH; gl 5+4/9; ECE; pos. margins; SVI; 2/4 Lt. pelvic nodes so orchiectomy done at time of R.P. 1 month post-op PSA 1.1 and 6 per day added 9/92 – PSA 0.01 until 12/03 PSA 0.10 3/04 – PSA 0.19 7/04 – flutamide D/C, PSA 0.6 9/04 – Consult; PSA 1.06; PSA DT < 2 mos. 9/04 start 9 mos. HB with KC, A/G, then EE; 15 doses T/E/C (9/04-2/05); AAC added as tolerated 4/05 – PSA nadir 0.03 6/15/06 – D/C HB; continue AAC; Start TRT

6/15/05 6/28/05 7/12/05 7/27/05 8/9/05 8/22/05 9/1/05 9/13/05 10/05 T < 20 725 2069 1831 2380 1501 1747 2578 1719 PSA 0.03 0.12 0.21 0.18 0.14 0.13 0.11 0.10 0.07

11/05 12/05 1/06 2/06 3/06 4/06 7/06 T 2680 2927 1406 2234 5731 2137 5407 PSA 0.05 0.05 0.04 0.05 0.04 0.04 0.06

4. Joe Y 11/93 – 51 years old; PSA 23; gl 3+4/7; pos. margins 3/94 – R.P. @ UCLA 12/94 – PSA 0.3 4/95 thru 6/95 – R.T. 12/97 – T 198, PSA 0.47 THB® x 16 months thru 3/99 9/00 – PSA 0.008, T 113; TRT started 11/00 1/01 4/01 7/01 10/01 1/02 6/02 10/02 1/03 T 274 438 186 338 598 256 581 404 1131 PSA 0.021 0.07 0.08 0.09 0.18 0.28 0.313 0.53 0.684

3/03 7/03 1/04 3/04 6/04 11/04 3/05 6/05 8/05 T 1055 3294 1395 1315 3015 1299 1250 2211 1395 PSA 1.12 0.9 1.24 1.66 1.4 1.66 1.74 1.18 1.72

10/05 11/05 12/05 1/06 2/06 3/06 4/06 5/06 7/06 T 1120 1707 1041 1130 655 798 339 1095 554 PSA 1.63 1.87 1.97 1.66 1.64 1.44 1.2 1.44 0.979

As of 3/06, on TRT for 5.5 years PSA rose less than 2.0 during that interval Joe literally told me that his life has been given back to him, including marked improvement in mental acuity

5. Dr. Earl S 5/89 - 59 years old; PSA 134; gl 7 C.T. – ECE & SV; L + KC 8/89 – R.P.@ UCLA; pos. urethral margins; PNI; ECE 10/89 – PSA zero (0) 4/92 PSA 2.0 1/96 – PSA 6.1 5/99 – Consult; PSA 11.99; T 228 Refused HB; Rx with finasteride, pamidronate, thalidomide PSA nadir 4.43%; T 170 6/02 – TRT started; PSA 6.86; T 278

10/02 TRT Dis- TRT 3/03 6/03 10/03 2/04 5/04 8/04 continued Restarted 11/21/02 2/6/03 T 714 380 2426 873 > 1600 1421 2345 3120 2478 PSA 11.3 15.0 12.4 13.2 12.5 13.5 14.1 15.2 19.0

11/04 2/05 5/05 6/05 7/05 8/05 10/05 11/05 12/05 T 1432 2280 > 1600 1458 2517 1069 1458 2371 1521 PSA 17.4 17.0 15.0 20.1 16.6 16.6 14.9 17.4 17.6

2/06 3/06 4/06 6/06 7/06 T 1545 1692 2986 1884 3521 PSA 19.6 16.0 17.4 16.0 17.0

5/99 - PSA 11.99; T 228 More than 7 years later - PSA 16; T 1692, with marked improvement in quality of life PSA rise less than 50 % in 7 years; From 5/99 thru 3/06 - PSA increased by 1/3 PSA DT > 15 years in spite of being on TRT since 6/02

6. Pat H 12/93 – 65 years old; R.P.; PSA 25; gl 4+3/7 @ JHH; pos. margins; ECE 1 mo. Post-op – PSA zero (0), but 6 months later – PSA 1.5 By 8/94 – PSA 18, meaning his PSADT was less than 1 month 12/94 – L + F x 1 year then L + one C thru 9/97, thus cycle #1 HB consists of CAB x 33 months PSA always < 0.07 on CAB 7/03 – T 246; PSA 0.011; TRT started

8/03 10/03 1/04 5/04 7/04 10/04 2/05 4/05 8/05 T 2057 1423 1113 1906 2783 2349 1486 2731 1157 PSA < 0.01 < 0.01 0.024 0.027 0.026 0.03 0.02 < 0.01 0.05

10/05 12/05 1/06 2/06 4/06 5/06 6/06 T 2464 1687 1616 1616 1970 2760 3716 PSA 0.05 0.03 0.04 0.04 0.06 0.06 0.074

7. John S 1/03 – 55 year old A.A.; PSA 7.7; gl 3+4/7; 6/6 cores; Endorectal MRI – ECE 3/03 – R.P. @ Memorial-Sloan Kettering; 2 pos. nodes; gl 4+4/8; SV pos. margins; ECE; 2500cc EBL 7/03 – PSA unmeasurable 12/03 – PSA 0.23 1/04 – PSA 0.35 4/04 – PSA 0.7 6/14/04 – PSA 1.02 8/4/04 – PSA 1.98; PSA DT 2 mos.; T 334; PAP 0.15 Rx 13 mos THB® (KC/HC), plus 15 doses T/E/C; AAC added as tolerated 8/05 – HB D/C; continue AAC and add high dose TRT

9/05 10/05 11/05 12/05 1/06 2/06 3/06 4/06 5/06 T 4064 3961 4421 2620 2433 2406 2901 2921 2815 PSA < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < .01

6/06 T 1708 PSA < .01

8. Fred W 11/99 – 67 years old; PSA 7.19; gl 4+3/7; T2a; T 308 6 out of 8 cores – path reviewed at JHH; clinical stage B1 11/99 to 12/00 – 13 months THB® with 3C 6/02 – TRT started; T 459; PSA 0.495 (but had risen from 0.22 to 0.495 in 9 mos)

9/01 3/02 Start TRT 7/02 9/02 11/02 2/03 4/03 8/03 6/02 T 417 435 459 1153 1003 634 814 3037 3550 PSA 0.22 0.42 0.495 1.53 0.612 1.32 1.09 1.08 2.33

11/03 2/04 5/04 8/04 11/04 2/05 5/05 9/05 11/05 T 1445 1348 1514 1786 1583 1150 > 1600 2592 3356 PSA 2.52 2.57 2.44 2.96 3.73 3.22 2.68 2.79 2.69

12/28/05 1/06 2/06 3/06 4/06 5/06 6/06 8/06 T 1828 1552 1744 4666 1957 3031 4117 2822 PSA 2.52 2.84 3.81 3.65 3.63 2.91 3.32 3.19

As of January 2006, in spite of being treated with TRT for more than 3 ½ years, his PSA did not quite double rising from 1.53 to 2.84. He is now on finasteride maintenance® therapy plus 1

9. Jerry H 11/96 – 72 years old; PSA 8.7; gl 4+4/8 1/97 – pos. bone scan; PSA 11; R.T. @ Cedar’s Sinai Hosp (7000 cGy) 8/97 – new mets on bone scan; PSA 17.5 9/97 – 13 months THB® – PSA zero (0) 12/01 – T < 100; PSA < 0.05; TRT started

12/02 4/03 9/03 1/04 6/04 10/04 12/04 3/05 5/05 T 1140 1151 1580 1328 1108 71 3828 911 880 PSA 0.083 0.104 0.217 0.264 0.535 0.039 0.319 0.341 0.524

6/05 8/05 9/05 T 1904 > 1600 > 1600 PSA 0.484 0.690 0.621

Expired 4/06 of acute myelogenous leukemia; Never had a recurrence of CaP.

10. Mike W 8/00 – 54 years old; PSA 7.18; gl 3+3/6; T1c; T 204 8 out of 10 cores involved – up to 80% of 1 core Seminoma, 1984 – surgery incl. abd. Nodes 11/00 – 12/01 – 13 months THB®, L plus 3 Casodex plus P 7/02 TRT started; PSA 0.153; T 396

11/02 3/03 5/03 6/03 9/03 11/03 1/04 5/04 8/04 T 1067 559 2485 1448 2306 535 1185 875 1471 PSA 0.7 1.2 1.44 1.55 1.58 1.7 1.61 1.86 1.7 12/04 3/05 6/10/05 6/23/05 8/05 9/05 10/05 12/05 2/2/06 T 1320 2464 1504 5154 1608 4066 1832 2054 1485 PSA 2.37 2.42 2.85 2.7 2.85 2.83 2.76 2.48 3.78

2/28/06 3/06 7/06 T 2342 4227 1389 PSA 3.77 2.73 3.12

11. Don B 6/99 – 56 years old; T2a; gl 3+4/7; PSA 6.82; T 462; cores positive > 50% 10/99 – 13 mos THB® with 3C 4/00 – 11/00, because of T 68-100, changed to 3 KC plus HC 30 mg 11/00 - D/C THB Then finasteride maintenance® therapy 9/02 – Start TRT

10/01 1/02 2/02 8/02 Start TRT 12/02 3/03 5/03 7/03 9/02 T 354 387 328 315 382 1041 1216 803 1178 PSA 1.49 2.04 2.84 2.32 2.6 2.76 3.26 3.41 4.4

9/03 12/03 3/04 7/04 10/04 1/05 3/05 7/05 9/05 T 1655 1419 1374 1187 2935 2241 1412 2353 1699 PSA 3.25 4.5 3.7 3.95 3.85 4.51 5.82 3.11 3.05

12/05 1/06 3/06 4/06 5/06 6/06 7/06 T 1974 1833 1788 1692 1491 1668 1739 PSA 3.62 3.08 3.31 3.64 3.95 3.43 3.87

12. Dr. Terry N – Veterinarian 2/99 – 66 years old; PSA 5.9 gl 3+4/7; PNI locally advanced; 4/5 cores; T 350 5/99 – F 250 mg BID; P x 2 weeks then added L 6/28/99 – COMG; PSA 0.69; T < 20 F changed to 3 C/day; THB® thru 6/00 1/03 PSA 0.6; T 332; Start TRT 2/03 4/03 7/03 10/03 11/03 1/04 3/04 6/04 8/04 T 604 553 1749 1556 1085 1152 1474 1544 1440 PSA 1.5 1.5 1.86 4.16 1.73 2.02 2.13 2.62 3.34

9/04 11/04 1/05 5/05 8/05 10/05 11/05 2/06 3/06 T 1189 1553 1830 > 1600 1064 1482 2665 3425 1510 PSA 2.01 3.41 1.78 2.44 3.14 4.53 3.49 4.48 6.02

4/10/06 4/19/06 5/10/06 5/31/06 6/06 7/06 T 2837 2665 3367 3401 3811 2153 PSA 8.1 6.16 4.92 6.2 5.88 4.29

As of 7/06, on High-Dose Testosterone for over 3.5 years PSA: 10/05 – 4.53; 7/06 – 4.29 Scans: 4/06 – no mets

* Originally presented at the Journal Club on 9/14/05

** Case reports presented at the Second International Study of Intermittent Therapy for Cancer of the Prostate – “Intermittent Androgen Supression: Seeking to lengthen the time off-treatment” (Vancouver, Canada; March 3, 2006)

® Triple Hormone Blockade, Triple Androgen Blockade, anLdeFgiennadstetroidAebMbraeivniteantiaonncse: are the registered trademarks of Robert L Leibowitz, M.D.

AR/aGth=eAr mthiannoglilumteithtihmeidneumber of TRT case reports, the editorEsCoEf P=AEAxtCraTcahpsauvleargEraxcteinosuioslny offered to pPuSAbli=shPrtohsetartemSpaeinciifnicgAenxtaigmenples in the upcoming A.A. = African American F = Flutamide PSADT= Prostate Specific Antigen Doubling Time ADAeCce=mAbnetria2n0g0io6gPenAicACCoTckntaeiwl sletter publication. gl = Gleason Score R.P. = Radical Prostatectomy BID = Twice a Day JHH = John’s Hopkins Hospital R.t. = Right C = Casodex KC = R.T. = Radiotherapy C.T. = Cat Scan L = Lupron Rx = Treat CAB = Continuous Androgen Blockade Lt. = Left SV = Seminal Vesicle CaP = Cancer of the Prostate mets = Metastasis T = Testosterone COMG = Compassionate Oncology Medical Group mg/day = Milligrams Per Day TAB® = Triple Androgen Blockade D/C = Discontinued nl = Normal T/E/C = Taxotere/Emcyt/Carboplatin DRE = Digital Rectal Exam P = Proscar THB® = Triple Hormone Blockade DT = Doubling Time PAP = Prostatic Acid Phosphatase TRT = Testosterone Replacement Therapy EBL = Estimated Blood Loss PNI = Perineural Invasion y/o = years old Pos. = Positive Z = Zoladex I would like to acknowledge the continued help of Joanna Tai, my office manager, in the preparation of these reports and the associated TRT manuscript.

PCRI Executive Director Brad Guess Dies Suddenly

Brad Guess, Executive Director of the Prostate Cancer Research Institute, passed away suddenly on Friday June 30th from a sudden heart attack. Brad had only been with PCRI for six months.

His work in the health field started when, as a result of a serious knee injury, he was forced to abandon hopes of a career in professional basketball (Brad was 6’8” tall). He was initially trained and licensed as a respiratory technologist and as such, he spent over 2 years in Thailand as a medical missionary. Subsequently Brad became a registered nurse and worked in the field of critical care. In 1997, he began his studies at Stanford to become a Physician’s Assistant. Initially he was employed in family practice and subsequently was hired by Healing Touch Oncology where he gained more than five years experience caring directly for men with prostate cancer.

Everyone who met Brad came away touched by his kindness and genuine concern for others. His many talents and skills simply magnified the impact of his compassionate and loving nature. Brad was 42 years old, and is survived by his two sons, Elijah and Benjamin.

California Regional Prostate Cancer Conference 2006

Improving Treatment and Quality of Life for Men with Recurrent or Advanced Prostate Cancer

When: Saturday, September 9, 2006 Where: Los Angeles, California State University Who Should Come: Men with Advanced Prostate Cancer, Recurrent Prostate Cancer, Incontinence or Erectile Dysfunction, their Partners or Family Members. Cost: $35 per person – includes parking, breakfast, lunch, afternoon snack, and printed program.

For information and registration, access www.pcri.org or call 310-743-2117.

Speakers: Glenn Tisman, MD (Medical Oncologist), Whittier, CA Duke Bahn, MD (Radiologist), Ventura, CA Hossein Jadvar, MD, PhD, MPH (Radiologist), Los Angeles, CA Mark Scholz, MD (Medical Oncologist) Marina del Rey, CA Jacek Pinski, MD, PhD (Medical Oncologist), Los Angeles, CA Harry Pinchot, PCRI Program Director & Patient Advocate Mitchell Gross, MD, PhD (Medical Oncologist), Los Angeles, CA Stanley Brosman, MD (Urologist), Santa Monica, CA Richard Lam, MD (Medical Oncologist), Marina del Rey, CA Karyn Eilber, MD (Urologist), Los Angeles, CA Prostate Cancer Risk Linked to DNA – Finding May Lead to Genetic Test Originally printed in The Grand Rapids Press May 8, 2006 – The Associated Press

New York – Scientists have identified a common genetic marker that signals a 60 percent heightened risk of prostate can- cer in men who carry it, and it may help explain why black men are unusually prone to the disease, a new study says.

The DNA variant may play a role in about 8 percent of prostate cancers in men of European extraction and 16 percent of the cancers in blacks, researchers said.

The study was published online Sunday by Nature Genetics and will appear in the journal’s June Issue. The work, draw- ing on study populations in Michigan, Illinois, Iceland and Sweden, was reported by Kari Stefansson and colleagues at de- Code genetics in Reykjavik, Iceland, and scientists elsewhere.

The variant is about twice as common in blacks as whites, so that may contribute to the higher incidence of prostate can- cer in blacks, the researchers said.

Stefansson said deCode planned to use the discovery to develop a genetic test that might help doctors decide how closely to follow men at high risk and how to treat prostate cancer cases. The study indicated the variant might be associated with more aggressive forms of the disease.

It is not clear whether the heightened risk comes from the variant or from another that lies nearby on chromosome 8.

In general, men run a 1-in-6 chance of developing prostate cancer. The risk is greater for those who are older, black or have a brother or father who has had the disease. More than 230,000 new cases are expected this year in the United States, with about 27,000 deaths.