We al are very familiar with the significant problem in the treatment of prostate cancer, even therapies that initially work stop working and our disease continues to progress. The inevitable onset of this resistance to treatment with antiandrogens (ADT) such as Lupron or Zoladex is not limited just to this class of drugs. We have seen that even in the newly approved drug Zytiga (abiraterone) is subject to this resistance problem. Similarly, resistance also develops in some men being treated with the 5ar-inhibitors that prevent a man’s body from synthesizing testosterone and dihydrotestosterone (DHT), the fuel for prostate cancer.
ADT is designed to tamp down prostate cancer by blocking the production of testosterone and causing tumor cells to die. As a result, levels of PSA (prostate-specific antigen) are lowered. However, when starved of normal testosterone levels, the body is able to compensate by synthesizing testosterone and DHT (androgens) through alternate mechanisms.
It has been believed that androgen synthesis and the resulting resistance to treatment was accomplished in one process (pathway) in which a hormonal steroid—androstenedione (AD)—is created through a biosynthetic process using an enzyme known as CYP17A. AD would then create testosterone and the testosterone would subsequently create DHT. DHT is a powerful testosterone metabolite with two extra hydrogen atoms. Known by many men as the fuel for male pattern baldness, DHT is 10 times more powerful than testosterone for driving the growth, invasion and survival of advanced prostate cancer.
In a Prostate Cancer Foundation supported research project Nima Sharifi, MD, at UT Southwestern Medical Center in Texas, has discovered a second, alternative biosynthetic pathway. This new pathway supports the synthesis of DHT, but goes around testosterone. In some patients, Zytiga may be a “leaky drug” allowing some AD to continue being produced. In this pathway, the “leaked” AD binds with the enzyme SRD5A1 to create DHT. Dr. Sharifi’s discovery shows that prostate cancer cells can create their own DHT without testosterone.
“Our findings will change the framework for the way people think about this disease,” says Dr. Sharifi. “The general assumption is that the tumor accelerates through testosterone when, in fact, the pathway goes around it to the most potent hormone. We both found the existence of this pathway in models and patients, and have shown that these resistant tumors are clearly driven by this other pathway.”
The real excitement is that this discovery and validation of this new DHT-synthesis pathway will provide potential targets for new therapeutics for men resistant to ADT and CYP17A-inhibiting drugs such as Zytiga.
Joel T. Nowak, M.A., M.S.W.
December 12th 2009, I was diagnosed with aggressive Prostate Cancer. The doctor told me that I had a High Gleason cancer #8 at the time. March 22nd my urethra closed off from the cancer. I was scheduled for surgery on the 23rd. I had the surgery after they opened urethra the night before. In June my PSA came back at 2.2. It should have been less than .1. I went to the Kansas Cancer Center to schedule an appointment. I got an appointment the 12th of July. They give me a 4 month Lu Pron injection. August 18th my urethra closed again from the growth. I started radiation 1st of October for 39 treatments ending the last of November. I got a 1 month injection of Lu Pron in December, January and February. I had my PSA checked the 15th of April. It came back at 2.2. I received another 4 month Lu Pron injection August 18th and started Casodex 50 mg tablet daily. Casodex is supposed to stop production of Testosterone by the rest of my body that the Lu Pron doesn’t affect. The only side effects that I have is swelling of my ankles finger joint pain and a hot flash now and then. I’m waiting for the results at my appointment in December. I am very interested in finding new ways to cure this disease which I have.
I am sorry to hear your story. First I have to ask if your doctor is a medical oncologist and if he/she specializes in treating men with advanced prostate cancer. There are a few things that you mentioned that causes me to ask this question. It is vital that you have a doctor who is a specialist in advanced prostate cancer and is a trained medical oncologist, not a urologist. Based on your information, which is sketchy, I am surprised to hear about some aspects of your treatment.
I urge that you join our advanced prostate cancer on-line support group where 700 of us can provide you with guidance and support in dealing with this disease. The group is a yahoo group, so simply go to yahoo.com, search GROUPS and search for the advanced prostate cancer group.
To answer your question about finding ways to “cure this disease,” I sadly have to respond, based on your description of your situation, that it is not any longer curable. However, this does not mean that you will not live for many, many healthy and happy years I was diagnosed with prostate cancer over 11 years ago and I do feel that I am as healthy today as I was when diagnosed. There are many men in a similar situation, I even know men who were initially diagnosed 20 years ago. So, don’t become overwhelmed. There are many ways to manage this disease, make it into a chronic aliment that can be controlled. To do this you need to educate yourself about the disease, begin to share, with your doctors, your medical management going forward.
The fact that you have found this blog and are asking questions tells me that you will become an educated patient and live a good, long and healthy life.
Ik ben zelfstandige thuisverpleegster en heb een patiënt met gevorderde prostaatkanker. Er werd hem voorgesteld in te stappen in een behandeling met Abiraterone Acetaat 1g en Prednisone 5mg. Hij staat echter twijfelachtig t.o.v. deze behandeling, wat begrijpelijk is als je alle mogelijke bijwerkingen leest, en vraagt mij hierover raad. Zelf ken ik het ‘geneesmiddel’ niet en vind ook geen verhalen van patiënten die dit middel kennen/gebruiken. Ik heb hem gezegd dat de keuze volledig bij hem ligt voor het al of niet starten met deze behandeling, maar dat ik zou proberen wat meer informatie i.v.m. gebruik en reacties van eventuele personen die dit middel nemen, te vergaren zodat we misschien wat wijzer worden over de werking, bijwerkingen en/of resultaten.
Hopelijk kunt u mij meer informatie verschaffen hieromtrent.
Met dank bij voorbaat.
I am self-employed home nurse and have a patient with advanced prostate cancer. It was suggested to him to step in treatment Abiraterone acetate 1g and Prednisone 5mg. However, he is questionable with respect to this treatment, which is understandable if you read all possible side effects, and asks me about advice. I know it yourself ‘medicine’ and do not find no stories of patients taking this medicine to know / use. I told him that the choice lies entirely with him on whether or not to start this treatment, but I’d try some more information regarding use and possible reactions of people who take this ground, to gather so we may become wiser about the effects, side effects and / or results.
Hopefully you can send me more information about this.
Thanks in advance.
I started using zytiga three months ago. This was after failure of the other main stream treatments surgery, hormonal treatment, chemo. I was diagnosed in 2005, with a gleason of 7.
i started zytiga(1g, 5 mg twice daily of prednisilone) when my PSA was 281. I was virtually asymtomatic at this time although the cancer had spread to my bones. Over the course of the next two months my psa went to a low of 259. By the latter part of the third month (two weeks ago) it went to 494.
During the first month on zytiga the only symptom I had was hot flashes. After that I started getting pains in my lower back and leg cramps and muscle weakness, at first in both legs then in one. Then i got a persistent pain in my right jaw and my alt and ast liver readings shot up. Most recently, i have been getting pains all over my skeletal frame and slight swelling under my armpits. I relieved the aches and pains with panadol 1g every couple of days. Some of the symtoms went away or improved over time.
After I got the 494 psa reading, I added avodart 3.5mg per day to my medication and reduced the preds to 5mg once per day. For about a week or so, this seemed to be associated with an elimination of the pain and muscle weakness..until last night when i had severe lower back pains.
I am just about to complete the third bottle of zytiga. i have ordered a fourth that I may never use, but just in case. It is hard to tell if all of the symptoms were caused by the zytiga. Some undoubtedly were, but clearly others could have been caused by the progression of the PC. I will know for sure when I do my blood work and scans next week and hear what my Onco has to say.
Yesterday, two weeks after adding the avodart to the zytiga, my PSA was down to 450 from 494. Virtually all of the aches and pains are gone, except for a slight soreness at the base of my spine. Its early days yet, but I am thnkful for small mercies.
I atarted my fourth bottle of zytiga to day and will continue with the 3.5 mg avodart daily and the preds, back up to 10 mg on the advise of my onco, and see what happens in a couple of weeks.
I have had similar experience with zytiga—asymptomatic when I started the regime but have had pain on and off while on the zytiga. My onc. is taking me off of the drug now that the psa went from 185 to 261 in the last month. That was my 5th month on the drug. Previous 4 months I had reduction of psa from 189 to 137 and back up again. I am interested in knowing if the avodart has continued to work for you in eliminating pain and reducing psa.
After all treatments failed over 10 years I was given zytiga in september 2011. I stayed on for a month and one half and got very sick. My liver would not process the drug and a buildup occoured. My side effects were unmanageable. Uncontrolled diareah, weakness, bone pain,loss of appa. tite,lost 30 pounds,trouble sleeping etc. Had to stop taking after 1 and 1/2 months. Tried reducing dose but it did not help. Showed a slight drop in PSA from 450 to 425.MRI showed that leasons grew after radiation. Don’t know what next step will be. Meeting Tuesday with doctor to check progress and next step to take.
Hello, i wanted to share my father’s experience with zytiga.
PSA 20.8 1/16/2012 start eith zytiga
PSA 5 1/30/2012
PSA 1.1 2/14/2012
Side effects, headacke. We are watching the blood presure and the liver functio the blood tests show little elevations but the doctor is not alarmed, however i saw on the blood tests a measure of free hemoglobin that is 3 times higher than normal, the doctors didn’ commented on it but when i compare other blood tests done this measure was never tested before so i wonder since they have now included it after the start of the zytiga itmust tell them something.
Please note he is not taking prednisone, due to other medical condition.
Any clues what this free hemoglobin can mean in my father’s case.
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