Advanced Prostate Cancer Teleconference 25 May 2012

[Euan]

Sorry this is a little late.

Man #1 reports that after a PET scan showed a hot spot. A subsequent MRI showed that he had a cancer in his neck. It is next to his tonsils and about the size of a 50-cent piece. Very unlikely to be from his prostate cancer but it is potentially major surgery. Man #2 said that just 5 weeks earlier he had a benign tumour removed from his parotid gland and it was a 2.5-hour surgery. Man #3 said that his body scan for prostate cancer showed a cancer on his kidney so he had to have his kidney removed.

Man #4 said that he has been on an abiraterone trial since October 2011. He is one of the unlucky non-responders and has now come off the trial after 8 months because his PSA has continued to rise, currently 17 or 18. He was getting vomiting, illness and a fair bit of pain and was in hospital for 5 nights. He is now on another chemotherapy drug mitozantrone and another steroid called dexamethasone (Dexmethsone®). Mitozantrone is much less toxic and much less potent than docetaxel (Taxotere®). He has a lot of bone pain from his metastases but just one week after starting mitozantrone it has considerably reduced. He also mentioned that it was a deep blue and his pee is now quite blue. Man #2 commented that mitozantrone is well known to relieve pain. He also pointed out that some men respond to some treatments but not to others. You need to find which treatment works for you. Also, he mentioned that after being off Taxotere for a while when you go back on you can get another benefit. Man #5 also agreed that you must try these treatments as you might receive significant benefit.

Man #6 said he was part of a study being done by the Princess Alexandra Hospital (PAH) looking for prostate cancer markers to improve on the PSA test. The trial duration is one year and is only for men with advanced or metastatic cancer. It involves a blood test at the PAH every 6 weeks and they advise you of your PSA.

Man #7 told of the 100k bike ride in Toowoomba and the older men said that they had to stop their bike riding before having a PSA test. Others agreed that bike riding could affect PSA as can sexual activity.

Man #2 began his talk by pointing out that although all types of prostate cancer start in the prostate they are not all the same - there are many kinds. At the very simplest level, some doctors informally divide prostate cancers into "pussy-cat" and "tiger" varieties; the first only has a gentle effect on the man, the second races and rages.

The next division is made by taking samples from the prostate with a biopsy. The cancers are classified by how messy the cells look. If the cells have neat outlines, and are packed fairly neatly, they are called "well differentiated"; if they have messy outlines and are messily packed they are called "poorly differentiated". Donald Gleason gave doctors a way of scoring the messiness, with the most messy getting higher Gleason scores - 10 is the highest. Looking carefully at the prostate biopsy cells under the microscope identified half a dozen or so different types of prostate cancer cells by their shape – one "small cell" type turning out to be particularly active.

Doctors experience has led them to recognize different types of prostate cancer by the way they show themselves. One doctor, for instance, reports that men whose PSA is always very low as their disease clearly progresses are very difficult to treat successfully; men whose PSA suddenly goes very high often have lymph-node only progression, and are often successfully treated by radiation to the lymph node.

Most recently we have the ability to examine the very combinations of molecules (the genes in the DNA) that help make up prostate cancer cells. At last count I heard reported some 28 different strains of prostate cancer found this way.

Adding to this complex picture, men have been reported to have more than one of these strains in their prostate, and indeed, sometimes more than one of these strains in a single biopsy core sample. This variety of prostate cancer types is one reason that every man's prostate cancer journey is different.

Man #2 went on to say that a recent study has reported that for locally advanced cancer high dose rate brachytherapy plus external beam radiotherapy has better outcomes than surgery plus external beam.

Zoledronic acid (Zometa®) is very commonly used to slow down prostate cancer in your bones. It can cause a nasty condition known as osteonecrosis of the jaw. If you have to have a tooth extraction while on Zometa a very small study had success using Plasma Rich in Growth Factor (PRGF).

The antiandrogen bicalutamide (Cosudex®) a non-steroid is reported as much better over long term use then cyproterone acetate (Androcur®) a steroid. For short-term use such as suppression of flare both are equally effective.

For some men on an LHRH analogue (hormone therapy) their testosterone does not get low enough so that it is important to monitor testosterone levels. If your PSA is not falling rapidly this may be the cause. Some men are on high doses of an antiandrogen such as Cosudex, often because they wish to continue their sex life. This leaves ones testosterone circulating but blocks the cells from taking it up. However, this method is reported to be not as effective at combating prostate cancer when used alone.

Man #1 said that the Zometa he was taking monthly was to prevent osteoporosis and the loss of bone but was not also being tested for testosterone. Man #3 said he thought that Dr Snuffy Myers was making the point that when men come off androgen deprivation therapy (ADT) some men get no recovery of their testosterone. Man #6 asked if there was a paper recommending testosterone testing with LHRH analogues.

Note: one such review is “Incomplete Testosterone Suppression in Prostate Cancer” http://www.nejm.org/doi/full/10.1056/NEJMc1010187 .

Man #2 said that Zometa keeps you bones stronger but also keeps you alive longer presumably by keeping prostate cancer from securing more footholds in your bones. Man #6 said that he was initially on monthly Zometa infusions but other doctors have said that Zometa can be extended and he is now on 6 weekly infusions. Man #5 suggested that based on his experience it might be advisable to initially start on monthly infusions to get the initial hit and then go onto a longer interval. Man #2 said that the Federal Drug Administration had declined to approve Zometa for prophylactic (preventative) use. Man #8 commented that there was a new drug already approved and on the PBS called denosumab (Xgeva®) which is reported to be slightly better than Zometa. Man #2 said that unfortunately it also has the necrosis problem. Man #5 strongly recommended to make sure that you had your teeth thoroughly checked and all work done before you start on Zometa. He explained that Zometa works by inhibiting your osteoclasts from nibbling away at your old bone. Man #1 said that his oncologist wants him to go on Zometa but because of his ongoing problem with his teeth he is staying on strontium ranelate (Protos®) for his osteoporosis. Note: Protos is a bisphosphonate.

Man #5 said there was to be a mail out of 2000 copies of Dr Myers books. One is called “Beating Prostate Cancer: Hormonal Therapy and Diet”. Both man #5 and man #2 said they have read the book.

Man #6 said that for him the side effects from Androcur were horrendous. The Cosudex side effects he found were not too bad. Another member had a similar experience. Man # 8 commented that Androcur is listed on the PBS for Advanced carcinoma of the prostate; To reduce drive in sexual deviations in males.

Man #6 asked about articles on the need to test for testosterone when on LHRH analogue. (Here is one: “Incomplete Testosterone Suppression in Prostate Cancer” http://www.nejm.org/doi/full/10.1056/NEJMc1010187).

Man #9 told of being approached by Ethical Strategies, a public relations firm, working on behalf of Janssen-cilag a subsidiary of Johnson and Johnson. They are developing an awareness campaign on prostate cancer called Tomorrow Counts. They will be developing a coffee table book with 10 or 12 men with pictures and their stories. They are also preparing a website which should be ready within a few weeks which will include videos of these men. There is an open invitation for everyone to get involved.

Man #2 read a study which said that for men who had radiation only or hormone therapy alone a longer time to reach PSA low point (nadir) had a better outcome. When primary hormone therapy fails, secondary hormone therapy may work in 30% of cases. If it fails in less than 12 months or never went under 0.2 then you are unlikely to benefit from secondary hormone therapy and early chemotherapy may be a better option. If primary ADT is just injections then adding bicalutamide (Cosudex®) or nilutamide (Anandron®) or flutamide (Eulexin®) often work. Plus rotating them may also work. Ketoconazole (Nizoral®) is much stronger than the others but affects other drugs.

For elderly men or men in poor health then weekly chemotherapy with docetaxel (Taxotere®) is more gentle and just as effective. Docetaxel can also be used intermittently plus going on to another drug then coming back to docetaxel can also show benefits. Man #9 said that only about half of men get benefit from docetaxel.

Man #8 said that in Japan their primary hormone therapy is a LHRH agonist (eg Zoladex) combined with an antiandrogen (eg Cosudex). They then do not stop once the PSA becomes undetectable or reaches its low point but continue for at least 3 years. Labrie in Quebec City recommends 7 years for European men. This comes at extra costs, both financial and quality of life.

Man #9 said that he has heard that switching from and LHRH agonist eg Zoladex to the new LHRH antagonist degarelix (Firmagon®) can sometimes give benefit when the other ones do not. Man #2 said that the use of oestrogen to lower testosterone was like antiandrogens alone - gentler but not as effective then the LHRH analogues. It is most commonly used in elderly men. Oestrogen tablets should be avoided as they can lead to cardiac problems.

Man #2 continued with a study on survival. If you had biological recurrence with 1 year of treatment then you have only a 44% chance of surviving a further 5 years. However, if biological recurrence occurs at 4 years then you have a 90% chance of surviving a further 5 years.

Abiraterone (Zytiga®) and cabazitaxel (Jevtana®) can only be given when a man is not too sick. For this reason docetaxel is best given early. Note: abiraterone and cabazitaxel were both recently recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) but not are yet on the PBS. They will then only be for use following chemotherapy.

Convenor Jim Marshall is requesting home addresses so that they can be sent to PCFA and he also has brochures from the multi disciplinary team to be mailed out. Therefore please email Jim with your address.