INTRODUCTION
Here we pick up the story at the end of Chapter Two. The chart below shows my PSA in the months following the Provenge dendritic cell vaccine, and as you can see, the vaccine did work. My PSA never went much over 6.0 for the better part of a year. That's the good news. The bad news is that it stopped working about in July of 2001.
Not only did my PSA start going up dramatically in July, 2001, but also my Alkaline Phosphatase began to rise rapidly:
A Bone Scan Tells the Story
This increase in both PSA and Alkaline Phosphatase was noticed first by Dr. Weber, who then suggested that I get a bone scan as soon as possible. I did so on July 31st, and the results are shown, in part, below, compared with an earlier bone scan done when I had started my initial hormone blockade.
Needless to say, this was a disconcerting development. (English translation: "It scared the s--t out of me!") Popular belief at that time held that when bone metastases appeared in large numbers, one's lifespan in months could be counted on the fingers of one hand. This was not good!
Fortunately, I had learned by this time not to panic at the sight of what seemed to be very bad news. Looking a bit more objectively at this, I noted that I had no bone pain to speak of, and I was not on any medication. In fact I had not been on any hormone blockade for well over two years. At this point, Drs, Weber and Pomeroy both agreed that I should immediately return to the hormone blockade treatment regime which I had been on earlier. Dr. Small also agreed when I spoke with him later, and was very encouraging about the likely results of this treatment.
So, on August 1st, 2001 I resumed the "triple hormone blockade" consisting of monthly Lupron injections, bicalutamide (Casodex) anti-androgen, and finasteride (Proscar) a "5-alpha-reductase inhibitor." If you are interested in learning more about the story behind these drugs, you can find a brief article on our support group website. As you can see, the results were quite quick and dramatic. In five months my PSA steadily dropped until it reached a nadir (lowest point) of 0.5. And my Alkaline Phosphatase went baack down as well. What is more important, a bone scan a few months later showed that virtually all of the metastases had disappeared, much to my relief.
I should add that, except for a few days off for visits to out-of-town doctors, I continued to work full time at my job throughout all of this. This included time while being treated at UCSF and Loma Linda, where I telecommuted and brought along prototype equipment I was testing. At this point I felt that I did not want this illness to slow me down or be a hindrance to my many day-to-day activities. And there was much going on in my personal life, as well. Two daughters got married, and gave us two wonderful grandchildren.
Almost a Tragedy
But not everything in my world was good news. Just about the time I had my cancer back under control, my two-year-old grandson Brandon was diagnosed with Wilms' Tumor, a kidney cancer. I never thought I would ever hear worse news than my diagnosis of prostate cancer, but this was much worse. How could this happen to a wonderful little boy who had so much to look forward to? I was devastated. But my daughter and son-in-law were very brave, and never doubted for one minute that Brandon would be made well again. As soon as they could, they took him to the Lucille Packard Children's Hospital at Stanford for evaluation by a team of specialists.
The news was not good: both of his kidneys were heavily burdened with tumors, and the doctors at Stanford agreed that one of the kidneys must be removed immediately. This was the beginning of many long visits to Stanford, which ended in a 14 hour marathon surgical session in which Brandon's one remaining kidney was removed, the cancer was cut out, then the kidney was treated with radiation, and finally put back into his body. This kind of procedure had only been done once before in the entire world. It is to the tremendous credit of Drs. Larry Moss and Oscar Salvatierra of the Stanford medical faculty, that they could put together a team of 12 specialists capable of such a feat. Brandon is now doing incredibly well, and has little or no memory of his ordeal. His story was written up in the Stanford Report for March 2002.
On to the Hormone Blockade
2001 marked the beginning of a whole new adventure: living with Hormone Blockade in its many forms. When I first was diagnosed with prostate cancer and began hormone treatments, most doctors believed that these were very "benign" treatments with minimal side effects. This was the atmosphere that surrounded my initial Hormone Blockade in 1997. I was told that I would have little transient, and no permanent effects from the use of Lupron. This turned out to be a bit too optimistic! While Hormone Blockade, also known as "Androgen Deprivation Therapy" is not toxic in the same way that, say, chemotherapy agents are, it turns out to have some insidious long term effects. In the last few years, I have learned about these effects, sometimes the hard way.
So Hormone Blockade is a two-edged sword: it can be a very effective treatment for what otherwise is a fatal, incurable disease, but it also causes a number of problems. The most well-known of these is sexual dysfunction. To put it succinctly, Hormone Blockade is a fancy way of saying "chemical castration." You see, the hormone which causes prostate cancer to grow, and is being blocked by Hormone Blockade, is testosterone. And testosterone's most imortant role is to provide the power behind male sexuality. Without it, a man will lack "libido" (sex drive) and usually will experience erectile dysfunction (E.D. or impotence). Now I remember reading in the works of Plato, that he lamented the years that men spend "lusting after women" as a waste of time. He claimed that he really didn't start doing any serious thinking until his later years when these urges began to dissipate. However not everyone shares this view! Especially when it happens before reaching those "later years."
As if that were not enough, there is more. You see, testosterone is more than just a "sex potion." It has many other more subtle effects, and the lack of it reveals a multitude of these effects in their absence. To name just a few, testosterone keeps bones strong by enabling the use of calcium to create bone tissue. The lack of it can result in osteoporosis. Also testosterone drives the metabolism to use food to build muscle tissue. The lack of it results in a slower metabolism, lower energy level, and food being turned into fat instead of muscle. Finally, testosterone has subtle but widespread effects on the brain and nervous system, keeping it "tuned up" and running at peak performance. The lack of testosterone may be manifested by short-term memory loss, slower reflexes, and lack of the ability to concentrate or think clearly. Many men jokingly refer to this as the "Lupron Fog" that makes them forget their anniversaries, and lose their car keys.
Fortunately there are solutions to some of these problems. Sexual dysfunction may be helped by drugs such as Viagra, or by surgical implants. Bone integrity can be maintained by the use of bisphosphonates (although these have their own set of side effects.) Weight gain can be managed by diet and exercise, and short term memory loss can be helped by artificial means, such as pocket PC's. I guess the bottom line is that until we have a real cure for cancer, this is better than the alternative...
But enough whining and complaining! Let's move on to the next part of our story. The longer term results of the renewed Hormone Blockade are shown in the chart below.
Dr.Ryan
A New Drug and a New Doctor
The combination of Lupron, Casodex and Proscar worked nicely for about a year. During this time, a few other changes happened. On occasions when Dr. Small was not available at UCSF, I saw Dr. Charles Ryan, Assistant Clinical Professor of Medicine. Dr. Ryan is in charge of most of the prostate cancer related clinical trials at UCSF Cancer Center, and is particularly knowledgable on the endocrinology (effect of hormones) of prostate cancer. Dr. Ryan is a very easy person for me to talk with, and he is willing to spend the extra time in answering my many questions. Meanwhile, Dr. Small was spending more and more time on the road, raising funds and doing "management" kinds of things. So when the staff at the Cancer Center asked for "volunteers" to see doctors other than Dr. Small, I decided that Dr. Ryan would be a good choice. I have been seeing him ever since.
Toward the end of 2002, it became fairly obvious that the combination of drugs that I was on was not working so well. My PSA had started to rise, and at this point some doctors would say that the cancer cells were becoming "hormone refractory." Fortunately for me, I had some pretty smart doctors, who had a few more tricks up their sleeve. Dr. Ryan's first suggestion was simply to stop the Casodex. This seems unusual, unless you know about the "Anti-Androgen Withdrawel Response" (AAWR) that sometimes happens if the cancer cells have learned how to feed on an anti-androgen such as Casodex. In my case, if you look at the months of October through December of 2002, you will see a slight but noticeable drop in PSA.
Unfortunately, the drop only lasted a few months, and then my PSA began to rise again. Interestingly, though it rose very slowly. While this was happening, Drs. Ryan and Pomeroy both were comfortable with my just staying on Lupron alone. But after about a year, my PSA was beginning to climb more rapidly, and October of 2003 Dr. Ryan suggested something rather surprising: go back on anti-androgen medication. But not Casodex - it seems that when the cancer cells learn to live on one anti-androgen, they may still be attacked by another. So I then went on a drug called nilutamide, with the trade name Nilandron. While my PSA didn't drop below 1.0, I still enjoyed almost another two years of relatively low PSA.
A Change in Lifestyle
All of this time I continued to work at my full time job as a project manager for a high tech company in Silicon Valley. But I could see that my performance was not what it used to be. I found it difficult to drag myself out of bed in the morning, I couldn't remember appointments, and worse yet I had started to have a hard time staying awake in meetings. Years earlier I had taken pride in having almost boundless energy. I worked nine or ten hours, and then came home and worked for another four or five on the new house we were building, and hardly noticed it. But now things were becoming painfully different. Largely because of the drugs, I was putting on weight, which seemed to compound the problem, and I felt like I was moving and thinking in slow motion.
Things were finally brought to a head when my boss told me that, due to a downturn in the economy, we would have to let a couple of people go. He asked for my suggestions as to which people to lay off, and in turn I told him that I felt I should be one of them. He was not happy with this suggestion and disagreed with my pessimistic self-assessment. But finally he agreed to put me on a long term disability with the proviso that I would be available for part-time consulting in return for having my medical insurance paid up for the next eighteen months. This seemed fair to me, so in March of 2003, I officially went on disability.
No sooner did all of this happen than I realised how much my work had dominated my life, and how little time I had been spending with my family. So in a way the change was actually a very positive thing. Even though I didn't feel too good, I could spend much more time with my family and grandchildren. One of my daughters had a plan to buy a hair salon and become a successful business person. Now I could spend some time helping her do this. I couldn't put anywhere near the energy into this kind of thing that I could have ten years earlier, but at least I was there.
Second Line Treatment: Ketoconazole
In the early part of 2005 my PSA again began to climb. This was an expected outcome as the cancer cells adapted to the nilutamide. But what to do next? Well, it turns out that there is another trick that can outfox the cancer cells. You see, anti-androgens work because Lupron doesn't stop all of the testosterone production in the body. A very small amount is manufactured by the adrenal glands, which sit on top of the kidneys. There is a sort of "back door" to produce testosterone by stimulating the adrenal glands with a substance called "ACTH" made by the pituitary gland, which causes the adrenals to convert cholesterol into a series of chemicals, ending up as testosterone. But this whole process can be shut down by a drug originally used as an anti-fungal called ketoconazole, trade name Nizoral.
So in May of 2005, I began taking 1200 milligrams per day of ketoconazole. Because the adrenal production of several other chemicals is also shut down, I also had to begin taking 30 milligrams of cortizone each day. Unfortunately ketoconazole is not as free from side effects as anti-androgens. Because it shuts down the adrenal glands, it causes a number of unpleasant problems: sticky skin, dry and cracked lips, transient nausea, and even less energy. No one knows if it is actually related, but about the same time I began taking keto, I started suffering from severe neuropathy in my feet. Even though I am no longer taking keto, the neuropathy remains to this day.
Zometa: Good News & Bad News
All the while this was going on, I continued to get monthly infusions of the bisphosphonate zoledronate (Zometa) for the purposes of maintaining bone integrity, and the benefit of increased resistance to bone metastases. During this time I had heard bits and pieces of information saying that bisphosphonates may cause problems with the jawbone and teeth. This never really sunk in until in the late part of 2005 I suddenly noticed that many of my teeth were loose. Now I am sure that this is partly my own fault, since dental work had kind of taken a low priority while all of this cancer fighting was going on. But there was no doubt that something had happened, and a few visits to oral surgeons confirmed that I had the beginnings of what is called osteonecrosis of the jaw, or ONJ for short. The story is that bisphosphonates harden bone, but at the expense of destroying the blood circulation in those bones. This means that the bone tissue is effectively dead. Now all that has to happen is for some bacteria to take up residence in the bone, and you can quickly have ONJ. Fortunately I got hooked up with a specialist who was very familiar with this problem. Although I was one of the few men he saw with this problem (most ONJ patients were women taking bisphosphonates for osteoporosis) he was confident that he could get the situation under control. Five months later, and minus six teeth, I am out of harm's way for ONJ.
Keto Fails
Well, this was bound to happen sooner or later - in early 2006, my PSA again began to climb. By June it had reached 7.0 and Drs. Ryan and Pomeroy both agreed that it was time to pull the plug on Keto. But what to do next? There were several clinical trials coming up for men in my situation. Also I had read in some of the writings of Dr. Charles "Snuffy" Myers, that a drug called Granulocyte-Macrophage Colony Stimulation Factor (GM-CSF for short) had helped people who were failing ketoconazole. Like the provenge vaccine, this drug stimulates the immune system to fight cancer cells. So what could be better? There was a bit of a problem, though: the stuff costs $300 a dose, and you get it daily for two weeks. That's $4200 for one month! So I decided to give it a try, unless something better came along. I didn't have to wait long for that to happen...