LIFEBUOYthe

Dear Readers Over the next few months there will be many activities involving awareness and fundraising in the area of prostate cancer. September is prostate cancer awareness month. I have listed a few of the events so that you can mark these in your diary and I hope that many of you will be part of one or several of these community events.

Sunday September 2nd was the “Fathers Day Fun Run” at Olympic Park. I hope that many of you were able to join in.

Monday September 10th is the PCFA “Inaugural Gala Dinner” at Doltone House at Darling Harbour. The dinner hopes to raise not only awareness in prostate cancer but funds for ongoing research and education. The concept of the evening of the four chefs came from a dinner hosted by the St Vincent’s Private Hospital Ladies Committee last year – of which part of the monies raised were donated to the St Vincent’s Prostate Cancer Centre. Once again the St Vincent’s team are very dynamic in their thinking and I am looking forward to a wonderful evening.

Thursday September 13th is the “Prostate Cancer Phone-In Day”. This is an annual event organised by the Cancer Council and enables the general public to phone in and ask any concerns that they may have in regards to prostatic conditions especially prostate cancer. The phones are manned by Cancer Council staff, medical and nursing staff and prostate cancer survivors. It is a wonderful service and last year 1,171 calls were received. It is a day that I enjoy being part of.

Sunday September 23rd is the “Men’s Health Promotion Conference” at Darling Harbour. This has been arranged by the PCFA and has been held in every state. The list of speakers is very distinguished and I am sure that all of them will make it a very informative and interesting day. The conference is open to both men and women.

November is “Movember” month. Men are encouraged to grow a moustache and be sponsored for doing so!

Michelle Pisani, a Physiotherapist from St Vincent’s was the guest speaker at our last Support Group Meeting on August 7th. Michelle’s talk on “Fighting Fit for Prostate Cancer” was most interesting and she told the audience how fitness through exercise and diet helps in the fight against cancer and decreases reoccurrence of the disease. In the next newsletter there will be a summary of her talk. The last meeting of the year on Wednesday November 14th is on “The role of MRI scanning in prostate cancer”. Dr David Ende, a Urologist from St Vincent’s, will be the guest speaker. Dr Ende did his phD on this topic and is currently conducting a study here at St Vincent’s looking at this subject.

As promised this edition of the “Lifebuoy” focuses on “Joe’s story”. In 2002 Joe at the age of 55 was diagnosed with metastatic prostate cancer. Today he is in remission and I am sure you will find his story interesting.

I would like on the behalf of the St Vincent’s group to congratulate Professor Dexter Dunphy who received an Order of Australia – Member (AM) – General Divison in the Queen’s Birthday Honours 2007. Dexter received his award for services to education and to the community. Dexter is the Chair of the PCFA’s Public Awareness & Education Committee and a Director on the National Board. Dexter was one of the people instrumental in forming the support group here at St Vincent’s – WELL DONE DEXTER !

Jayne MatthewsCo-ordinator St Vincent’s Prostate Cancer Centre

St Vincent’s Hospital

Prostate Cancer Support Group

affiliated with the

Prostate Cancer Foundation of Australia

IS

SU

E

3,

20

07

I hope my story might give hope to many who have been diagnosed with metastatic prostate cancer.

I was forced to retire suddenly from medical practice in September 2002 when I was diagnosed with widespread metastatic prostate cancer. I had never had any symptoms referable to my prostate. My metastases were scattered throughout my lungs, bones and an adrenal gland. I had early signs of spinal cord compression at two levels. My PSA was 554. I was only 55. I was given less than three years to live.

I’m embarrassed to say I hadn’t realised that prostate cancer was the most common cancer after skin cancer in men. And I’m embarrassed that, while I was beginning to think I’d reached an age where a good general check-up was in order, I hadn’t done anything about it.

At the outset, I was determined to try everything I could to arrest this disease. And if in the end this should all be in vain, at least I would know I had done my best. I’m happy to report that after almost five years I remain well, my current scans show no evidence of metastatic disease and my PSA is less than 0.01. Let me share my story with you.

Initial treatmentI was first given a course of radiotherapy and steroids to save my spinal cord. I also commenced first-line hormone therapy with Lucrin and Cosudex. The concept behind hormone therapy is that prostate cancer cells depend on testosterone to both survive and grow. Lucrin blocks the production of testosterone in the testes. Cosudex blocks the action of any remaining testosterone on these cancer cells. Of course, these drugs can cause side effects, but there are ways around most. From the outset I also began treatment with Zometa, Caltrate and Vitamin D to avoid osteoporosis that might result from this treatment.

My original oncologist wasn’t happy when I thought at the outset I should also see a urologist. What was the point. The disease had well and truly spread beyond the prostate and there was no place for surgery. I wasn’t happy with that, as I knew from my field that in a complex disease where many subspecialties are involved, each potentially has something unique to offer. Indeed there now seems to be a consensus that a team approach is best when dealing with advanced prostate cancer. At the very least, I think one should have both an oncologist and a urologist involved in their care.

There are a number of excellent urologists with a special interest in prostate cancer but I count myself very fortunate to have seen Professor Phillip Stricker just six weeks after my diagnosis. I asked him if he would consider a prostatectomy for me but, not unreasonably at that time, he recommended against it. From that moment, I made a point of following the literature closely to see if I could accumulate more evidence in favour of a prostatectomy for someone at my stage of the disease.

Dr Stricker was to do a lot for me. He went on to add Avodart (similar to Proscar), a drug that blocks the conversion of testosterone to dihydrotestosterone, which is 10 times more potent at stimulating prostate cancer growth. Some evidence suggests that Avodart appears to enhance the anti-cancer activity of Lucrin and Cosudex without adding more side effects. It is still not available in Australia and I’ve had to import it from overseas. Dr Stricker also tripled the dose of Cosudex as this may delay the development of resistance to hormone therapy.

He also started me on two supplements, Lycopene and Selenium, which have been shown to have some activity even in advanced prostate cancer.

It was in relation to diet and supplements that he first mentioned Dr Charles Myers, an authority on prostate cancer in the US, who writes a newsletter on this subject. I didn’t act on this at the time as I was perhaps a little sceptical of supplements and wanted to first concentrate on the mainstream literature and a possible cure. More about Dr Myers later.

After a month of first-line hormone therapy my PSA had fallen to 16. I was a responder. It took another 18 months to reach its lowest level, 0.2. But I knew this respite was unlikely to last.

Early signs of resistance to hormone therapyAfter 2½ years, interestingly following a period of stress, my PSA began to rise once more. In three short months it was up to 0.52 (I was now getting an ultrasensitive assay to two decimal places to monitor trends more closely).

My new oncologist handled this phase expeditiously. While I was to continue with Lucrin and Avodart, he suspended Cosudex, as a minority of patients will surprisingly respond to this, although usually only for a few months. It seems that in this minority the androgen receptor in the prostate cancer cell changes, and instead of being suppressed by Cosudex, this drug begins to have an opposite stimulatory effect. This move resulted in another reprieve. My PSA fell 50% over the next seven months. Incredibly, it hasn’t risen significantly since. While this may be due to good luck, it may also have been influenced in part by other measures we were to take.

Exploring the optionsThere’s nothing that focuses the mind more than when you learn you have entered an early phase of hormone-resistant prostate cancer. I began to review what was already known in the literature to see if it could be looked at in a different light. I will mention just two ideas here.

I knew that once the response to Cosudex withdrawal was over - and it was only a matter of time - there were perhaps three further options using second-line hormone therapy before complete hormone resistance took over. After that, therapeutic options would be limited, with life expectancy reduced to perhaps 18 months at best. Each of these options had between a 25% and 50% chance of halving the PSA. But the chances of success generally fall with each subsequent attempt and at best a positive response is usually measured in months, not years, as the cancer becomes resistant to each treatment in turn.

My response: Why wait for the PSA to start rising again before considering second-line hormone therapy. Surely this would allow the next generation of resistant prostate cancer cells to take hold before we lifted a finger. Why not hit the cancer while the PSA (and hence tumour bulk) was still low. There are many examples in the literature where cancer responds much better to treatment when it is given early. Also, why only give one of these drugs at a time, just waiting for resistance to occur. Why not give all three drugs together. After all, each of these drugs has been shown to attack the prostate cancer cell at different sites, which should increase their chance of success when given together. The fact that each of these drugs has different side effects may allow a patient to tolerate this combination quite well. Multi-targeted therapy like this has been used successfully in a number of other diseases where resistance is a problem eg. HIV and Malaria.

While Dr Stricker agreed with this concept, we would need the assistance of my oncologist. His response, however, was perhaps what all oncologists might have said in his place. Why rock the boat. I was doing well and this combined therapy was bound to cause more side effects. It’s interesting how things look so different when the tables are turned and the doctor becomes the patient. While I wasn’t happy with his response, I should add that I have never acted on anything unless I had the full support of at least one and preferably both doctors. More about this later.

While I had hit a speed bump, there was still the unresolved question of the role of a prostatectomy for me. I became more hopeful when I learned that patients whose renal cancer had metastasised beyond the kidney survived longer if they subsequently had their kidney removed, even though the horse had already bolted. Similar evidence may favour this approach with ovarian cancer and more recently with breast cancer too. Now we have indirect evidence that once prostate cancer has metastasised eg to bone, patients respond better to hormone therapy if they have had a previous prostatectomy. Certainly patients whose prostate cancer

Joe’s Journey

Next support group meetingn Wednesday November 14th 2007 - Dr David Ende “The Role of MRI Scanning in Prostate Cancer.”

Check the PCFA website for further details.

has spread only to the lymph nodes do much better with prostatectomy and hormone therapy than hormone therapy alone. Indeed, when patients with lymph node spread are treated with hormone therapy alone and followed until they become resistant to therapy, in more than half these patients hormone resistance first emerged in their prostate gland ie the cancer remaining in the prostate gland remains their biggest threat. Of course, whenever the prostate gland remains intact, it continues to be a potential source for further metastatic disease.

Around this time there was local TV coverage about a new technique for treating the prostate that may not have been quite as effective as a prostatectomy, but which was non-invasive and therefore safer. It could even be repeated later if necessary. This was high intensity focused ultrasound or HIFU. While not free of side effects, these are fewer. Luckily Dr Stricker had already performed this procedure a number of times, but of course only for patients with local disease. This procedure may not have been performed in anyone with widespread disease before, but after reviewing the literature, and with the knowledge that my prostate gland had shrunk from double to one-third normal size as a result of years of hormone therapy and that all scan evidence of metastatic disease had disappeared, he agreed to do it.

My HIFU was performed about four years into my illness and left me with no new problems. It wasn’t cheap, much of the cost coming from hiring the equipment, and none of it refundable as HIFU is clearly experimental in this setting. Following this, my PSA halved from 0.32 to 0.16. Good, but not good enough. There was clearly evidence of persisting micro-metastatic disease. There was still more to do.

Off to see Dr Myers in the USNow to a most important part of my story. Remember Dr Charles Myers? Well I hadn’t until by chance a fellow patient who had also been briefed on his virtues by Dr Stricker, actually got hold of some of his recent newsletters and showed them to me. I was flabbergasted. He didn’t just cover diet and supplementary therapy, important as I now realise these are. He covered all forms of treatment for all stages of prostate cancer. You can access his website at : www.prostateforum.com.

He has a very clear style of writing, perfect for patients without a medical background, and he displays a great ability to think outside the square. Indeed, such was the response to some of his latest newsletters that late last year he published a book (‘Beating Prostate Cancer: Hormonal Therapy and Diet’) that summarises most of his current ideas, particularly those relating to hormone therapy, diet, exercise and supplements.

Dr Myers has long been a professor of oncology and, importantly, a pharmacologist as well. For 10 years he was Chief of the Clinical Pharmacology Branch at the National Cancer Institute in the US. He has had a special interest in prostate cancer for many years. Sadly, what makes his current contribution so powerful is that at the age of 55, he too was diagnosed with prostate cancer that had already spread beyond the prostate, with evidence of microscopic spread to his bone. This event further sharpened his thinking and as a result of his innovative approach he, like many of his patients with advanced disease, remains well with a PSA of <0.01 and no evidence of metastatic disease - in his case seven years after diagnosis. While he retired from his university post following his diagnosis, he was able to return to private practice, specialising in prostate cancer, with, I suspect, a special interest in advanced disease.

Imagine my delight when I learnt he recommends second-line triple hormone therapy for patients at my stage of the disease, if first-line hormone therapy hasn’t reduced their PSA to <0.05. Indeed, Dr Myers has found this approach can even be effective in treating hormone resistant prostate cancer, even after chemotherapy has failed. And he advocates getting on to this early, not waiting for the disease to take hold. I’ve not read of anyone else who aspires to such specific and lofty goals in the treatment of widespread metastatic disease.

I clearly had to see this doctor and after completing a lengthy questionnaire I was given an appointment for March this year. I found him to be kind, thorough and most knowledgeable. And he was very generous with his time. As I had by then initiated his recommendations regarding diet, exercise and supplements (more about that later), he was able to concentrate on second-line triple hormone therapy. He suggested I start taking Ketoconazole, transdermal Estradiol and Leukine all together. Chasing a complete remission

He explains his approach this way. A number of cancers can now be cured, even if they are metastatic (eg. Lance Armstrong’s metastatic testicular cancer). But this is only possible if the patient achieves a complete remission. Without a complete remission, cure simply isn’t possible. He says it is possible to attain a complete remission in men with metastatic prostate cancer too. By this he means attaining a PSA of <0.05 (ideally <0.01) and having no bone or CT scan evidence of remaining cancer.

He divides treatment of metastatic prostate cancer into two phases. The first phase focuses on attaining a complete remission. The second phase is designed to prevent or delay the disease from recurring. For newly diagnosed men with metastatic disease, he first tries to induce a complete remission with first-line triple hormone therapy using drugs like Lucrin, Cosudex and Avodart. If this is not enough to place the patient into a complete remission, he moves straight on to second-line hormone therapy with Ketoconazole, transdermal estrogen and Leukine. He’ll only consider chemotherapy if this should not suffice, but finds this is often unnecessary.

While attaining a complete remission isn’t a cure, he feels it at least gives patients the best chance of long-term survival. But he emphasises this is only possible if they have ongoing treatment to maintain it.

Second-line hormone therapyKetoconazole helps wipe out the small amount of testosterone produced by the adrenal glands. It also directly attacks the prostate cancer itself. While it often caused significant side effects in the past when given in higher dosage, a recent study has shown that halving the dose eliminates most of these side effects and is just as effective. It’s important that Hydrocortisone be taken with Ketoconazole to prevent adrenal insufficiency. Dr Myers also recommends Ursofalk to prevent liver damage. Ketoconazole has a short half-life and must be taken eight-hourly by the clock. It is better absorbed if the stomach contents are acidic, and he recommends taking it with Coke. Ketoconazole blocks the conversion of Vitamin D into its active form, Calcitriol. He therefore increased my dose of Caltrate and Vitamin D, while ensuring I regularly monitored their blood levels. You can now begin to see the benefits of Dr Myers being an accomplished pharmacologist too.

Estrogen, taken by mouth, was for many years the main treatment for metastatic prostate cancer. It too reduced testosterone levels as well as directly attacking the prostate cancer itself. It was then discovered that it killed nearly as many patients as it saved, by increasing the incidence of serious vascular complications. Recently, several small studies have shown that transdermal estrogen patches may be just as effective if given in big enough dose and that giving it in this way appears to avoid these serious complications. For good measure Dr Myers has asked me to take 100mg of enteric-coated Aspirin daily, after breakfast, for added protection. He has found that estrogen further reduces the side effects of Ketoconazole. Indeed in my case it has improved my concentration, which had earlier been blunted by my original hormone therapy.

Leukine improves the body’s immune response to cancer. It has only recently been shown that adding Leukine to Ketoconazole greatly improves the outcome in patients with prostate cancer. In this study, Leukine was given two weeks in every four, but the PSA rose rapidly in the fortnight off treatment. Dr Myers noted another study where Leukine was given continuously for a different disorder without producing more side effects. So he now recommends his patients use it daily. Leukine is given as a subcutaneous injection. I should add that this drug is not available in Australia and is very expensive. I had to import it from the US.

At our meeting Dr Myers was confident I had an 80% chance of achieving a PSA of less than 0.01 with the triple therapy he proposed. Now that only comes from someone who really knows what he’s doing. Before starting this treatment my PSA had inched up to 0.22. I continued to monitor it fortnightly once treatment began. It dropped to 0.04, 0.02, 0.01 and finally, after just eight weeks, less than 0.01, which is as low as the laboratory can measure. I’ve just had my blood test at the end of my first three months of treatment and my PSA remains at <0.01. I am now in complete remission.

I suspect Dr Myers’ use of second-line hormone therapy is still evolving as he gains more experience with it. In response to my latest results, he has suspended Leukine for now, but asked me to continue with the remaining drugs for at least another three months, when I will return to the US for a follow-up visit.

Maintaining remission with diet, exercise and supplementsWhile I’m in remission, this is not a cure. The next challenge will be to maintain this remission. Diet, exercise and supplements will continue to play an important role. In addition, Dr Myers has written that certain drugs may have a part to play too. They include Avodart and Zometa, along with Celebrex, a drug I have also been taking. I had originally taken Celebrex for back pain, but continued to take it after my oncologist said it may have a role in advanced prostate cancer. I hope that low-dose Aspirin will protect me from the vascular complications Celebrex can sometimes cause. While I was already overweight at the time my disease was first diagnosed, I quickly became obese as a result of hormone therapy, my initial steroids playing a big part. Within a few months I had gained 16kg. While I initially tried to ignore it, the literature of late describes a strong association between obesity and more aggressive prostate cancer with poor outcome. So 10 months ago I resolved to do something about it. By limiting my calorie intake and walking 8-10 km a day I’ve managed to lose 60 pounds. (I’ve always made a practice of recording my weight gain in kg and weight loss in pounds. The numbers look better that way). Not only does exercise help with weight loss, it may help control prostate cancer growth, and it also helps control high blood pressure and diabetes, stress, osteoporosis and cancer-related fatigue. Dr Myers suggests exercising at least 30 minutes a day. Walking is fine.

Apart from encouraging weight loss where necessary, Dr Myers strongly promotes the Mediterranean diet. One study has shown that this can reduce prostate cancer progression by more than 60%. These are the main features: Reduce dietary fat. Avoid all fried foods. Avoid red meat. Skinless white meat such as chicken and turkey are fine, but avoid pork at all costs. Fish is important, particularly salmon, pink tuna, cod, herring and sardines, and ideally should be eaten at least three times a week. Avoid egg yolk and dairy fat, including butter and preferably margarine too. Skim milk, non-fat cheese and non-fat ice-cream are okay. You can eat dark chocolate in moderation too. Have plenty of fruit and vegetables, particularly tomatoes (especially as juice or cooked), pomegranates, cauliflower, broccoli, brussel sprouts, cabbage, onions and radishes. Other useful examples include beans, peas, lentils and dark grapes. While olive, avocado and hazelnut oil are good, avoid canola, vegetable and flaxseed oil. Bread, pasta, cereal and rice are good, but only in moderation because of their high caloric content. Almonds (with skin, rather raw than roasted), cashews, macadamia nuts, hazelnuts

and pistachios are good, but avoid peanuts, walnuts and pecans. You can have one or two glasses of red wine a day.

And finally, the supplements Dr Myers recommends: Vitamin D is the most important, 4000IU - 5000IU daily (levels should be monitored). Lycopene 10mg three times daily. Vitamin E, particularly as gamma tocopherol, no more than 200IU a day (Vitamin E in higher dosage may affect clotting, so care may be needed for those taking Warfarin or undergoing surgery). Selenium 200mcg a day. Fish oil, 2000mg twice daily (important to keep in a cool, dark place and once opened, store in fridge. Avoid using if it has a fishy smell as this means it has become rancid). Pomegranate juice 200ml a day (also keep in a cool, dark place and once opened store in fridge). Pomegranate also comes as a capsule (Life Extension brand best), but this is probably not as good as the juice. He recommends taking one capsule twice daily. Finally, soy isoflavones 100mg twice daily. (One must be careful and introduce soy separately while closely monitoring the PSA, as there have been rare cases where it has had the opposite effect). Please note that some supplements can be unreliable and I now source mine from the US. (Dr Myers recommends: Life Extension Foundation, www.LEF.org,

and iHerb, www.iherb.com). Indeed one can independently check the quality of individual supplements in the US at www.consumerlab.com.

These supplements, along with diet and exercise, have each been shown to slow the progress of prostate cancer. In addition, diet, exercise, vitamin D, fish oil, soy and pomegranate reduce the risk of cardiovascular disease, which is common in patients with prostate cancer, partly as a result of their hormone therapy. Of all patients diagnosed with prostate cancer only 40% will die from this cancer, while a further 30% will die from heart disease and stroke. Dr Myers emphasises the importance of treating the patient as a whole and does his best to avoid these vascular complications too. There’s no fun surviving advanced prostate cancer only to be struck down by a heart attack or stroke.

So you can see there really is a lot that can still be done for many patients with metastatic prostate cancer. And it’s heartening to know that knowledge in this field continues to expand rapidly. I recommend you subscribe to Dr Myers’ newsletter and read his latest book, ‘Beating Prostate Cancer’. You can see samples of both in Jayne’s office at St Vincents. It will empower you. Indeed Dr Myers believes

that patients do best if they are optimistic and forcefully manage the treatment of their disease. Most important, don’t give up. Life is too sweet

Joe Enis

If you would like to receive future newsletters and are not currently on our mailing list please complete and return the form below:

Name

Phone

Address

Please return to: St Vincent’s Prostate Cancer CentreSt Vincent’s ClinicSuite 508 - 438 Darlinghurst StreetDarlinghurst NSW 2010or email: jmatthews@stvincents.com.au

Call the Prostate Cancer Centre on 02 8382 6530 to borrow this book.

As you can see, Joe has researched his disease intensely and, to date, has had excellent results. Joe is a Specialist Medical Practitioner and he has used his medical knowledge to integrate very complex data, most of them untested, in a very pro-active, but sensible way. Clearly, at this stage, it has worked for him. I cannot emphasize enough that every patient is different and it is important to embark upon untested and novel treatments with your own Urologist and Medical Oncologist.

I, too, have been most impressed with Charles Myers’s approach to advanced disease and personally believe that his scientific, rigorous mind is challenging current dogma. I strongly commend you to read his books and website - www.prostateforum.com - as they give great hope. Above all, I urge all patients who are using Dr. Myers’s information to work closely in concert with their own Urologist and Medical Oncologist. I wish Joe a long remission and let’s all hope that he, and many other patients with advanced prostate cancer, can keep ahead of the pack by innovative doctors such as Charles Myers.

A/Prof. Phillip Stricker