For 13 years, Ken Gannon, 68, has been battling prostate cancer. Despite undergoing a radical prostatectomy, radiation therapy, and hormone therapy, Gannon was diagnosed in 2003 with androgen-independent prostate cancer (AIPC), also known as hormone-refractory prostate cancer. Primary hormone therapy was no longer keeping the disease in check. (Note: Although many patients request a psuedonym to protect their privacy, Ken Gannon and his wife, Linda, wanted to use their real names in this article. All medical details are as they reported. In keeping with editorial policy, the patient’s physicians are not named without their consent.)
Seeking to prolong his life — and possibly help his doctors find a drug that might heal other patients — Gannon began an odyssey through second-line hormone therapies, investigational drugs, and four clinical trials, one of which nearly killed him. Even so, Gannon’s view of clinical trials hasn’t soured, and he and his wife, Linda, both say he would willingly enroll in another one if it might yield some benefit.
Here, the Gannons and Glenn Bubley, M.D., an expert on AIPC at Boston’s Beth Israel Deaconess Medical Center and Ken’s urologic oncologist for the past six years, share details of Ken’s prostate cancer treatment and explain why they pursued clinical trials both before and after he was diagnosed with AIPC. Marc B. Garnick, M.D., guided the conversation.
How was your cancer diagnosed? What were your thoughts about the initial treatment?
KEN: I had had a PSA test and apparently the results were borderline. My physician called me back for a second test, and I passed it. But when I had another PSA test a year later, it had gone up to 8.5 ng/ml, so something was cooking. The doctor felt some hard spots during the digital rectal exam, so I had a biopsy in December 1995. It came back positive.
BUBLEY: Do you remember your Gleason score?
KEN: I think it was a 4 + 3 on the Gleason scale, for a total of 7. The highest is 10, so I had a moderately aggressive cancer.
BUBLEY: That’s why you decided to have surgery in April 1996.
KEN: Yes. Between the diagnosis and the surgery, I took hormones to keep the cancer in check. My PSA went down to 0 ng/ml just before the surgery. (See “Hormone therapy before surgery,” below.)
How did the hormones make you feel?
KEN: Very tired. I had been very active. I used to jog six miles a day. I couldn’t do that any more. I was always tired and couldn’t do what I wanted to do.
In the aftermath of the surgery, I was kind of upset that I didn’t do a little more research to find out who does the surgery and how often. Do they do the surgery every day? Looking back at my notes, I realized the surgeon I had did surgery once a week only. When he did my operation, he indicated that it was a complete cure. He took surrounding tissues, and the pathology report said everything was fine. I was considered completely cured. But shortly after that, my PSA started to climb again.
Hormone therapy before surgery
Years ago, patients often took hormones prior to a radical prostatectomy, a regimen called neoadjuvant hormone therapy, to shrink the primary tumor and eradicate micrometastases. Short-term studies showed that neoadjuvant hormone therapy reduced the risk of finding a positive margin in the excised tissue. But longer-term studies indicated that it does not extend time to biochemical recurrence or improve survival, making neoadjuvant hormone therapy much less common today.
So what did you do?
KEN: Well, it seemed that the only option was radiation. So I went for six or seven weeks of radiation therapy. That was in 1997.
Did you have any side effects from the radiation? What happened to your PSA?
KEN: I didn’t have any side effects, except for feeling a little bit tired and drained. I really didn’t have much difficulty with it at all.
When I started radiation therapy, I think my PSA was around 3 ng/ml, and when I completed the radiation, it had gone down to 2 ng/ml. So that wasn’t much of a knockdown. We didn’t have a good feeling about it, but I didn’t want to go on hormones.
BUBLEY: You had been on hormone therapy before surgery, and it didn’t make you feel very good. Is that why you wanted to avoid it?
KEN: Yes. I decided to get involved with a couple of clinical trials. The first was a trial of vaccines made with vaccinia virus and fowlpox virus. And the second was a trial of a diabetes drug, Rezulin (troglitazone), that researchers thought might slow prostate cancer.
BUBLEY: Fowlpox and vaccinia are cousins of the smallpox virus. Before they are injected, the bad parts of the viruses are removed and the PSA gene is added into them. Researchers randomly assigned participants to vaccines made from the vaccinia virus or the fowlpox virus, asking which one would be better at controlling prostate cancer progression.
Even though these are attenuated vaccines, they are theoretically infectious. They have to be given in a room that is washed down before and after administration. The nurse comes in wearing a mask, gown, and gloves. It’s not quite like having surgery, but patients remember the process as seeming very high-tech. There really isn’t much to it, but this is what we’re mandated to do.
What do you remember about the trial, Ken?
KEN: I was a little afraid because they had me in this big room and everyone was wearing masks to inject me. And then they kept looking at my arm for a big red spot, which would signal an allergic reaction, but I didn’t have one. And I didn’t have any side effects from the injections.
I was scared, but I was also hopeful that they would work, that they would knock down my PSA. But they really didn’t do much. The vaccines just kept the PSA steady.
How did you decide to try the vaccines, which were — and still are — investigational, instead of hormone therapy? What risks and benefits did you weigh?
KEN: Well, my wife is always with me when it comes to making every decision about my treatment. We’re willing to enroll in a study if it seems promising and might help me and others. If anything seems too far-fetched, we won’t go along with it.
For my initial treatment, I could have had radiation or surgery. At the time, surgery was considered the Cadillac of treatments. And because the doctors felt they could get rid of the cancer by cutting it out, we went with surgery.
As far as the fowlpox-vaccinia trial, my wife and I had discussions about it before I did anything. Our thought was that it might be beneficial. No one knew for sure; that’s why it’s a trial. But I didn’t want to go on hormones. I thought, “Maybe I’ll be there early when things happen and be a part of it.”
BUBLEY: Did the fact that the trial didn’t have a placebo make it more attractive?
KEN: Well, yes. I’m really not too fond of placebo trials. I see the need for them, but when you want your disease to improve, I think it tears you down a little bit if there’s a chance you could be getting the placebo.
In the fowlpox-vaccinia trial, everyone was getting a treatment. It didn’t lower my PSA, though. It held pretty steady, only rising very slowly. It wasn’t making drastic jumps, so I stuck with it for a while.
BUBLEY: One of the hopes was, and still is, that even if the vaccines didn’t make the PSA go down, they would at least hold the PSA steady or slow its rise. The goal: to spur patients’ white blood cells to seek out and destroy PSA-producing cells, slowing disease progression.
The vaccines have been tweaked in recent years. They are more powerful than they were in 1998 when Ken participated in the clinical trial, and researchers are seeing better PSA responses in some patients.
KEN: The injections really didn’t work the way I had hoped. Maybe they helped for a few months, but I knew I had to try another therapy. Another doctor suggested a trial of a diabetes drug.
How did you feel about enrolling in another trial?
KEN: Well, I was a little hesitant. I’m a type 1 diabetic, and troglitazone is a diabetes medication. I take insulin, and I was worried about how it would react with insulin. In theory, my blood sugar could have gone too low, but in actuality, it didn’t affect my blood sugar too much. I was also hesitant because I heard it was outlawed in England after causing liver problems. But I went ahead with it. It wasn’t really beneficial. It didn’t help my PSA at all, so I weaned my way off of it and dropped out of that study. Troglitazone was subsequently taken off the market in the United States.
BUBLEY: Could you have been on a placebo?
KEN: It wasn’t a placebo, no. Everyone got the actual drug.
What happened next?
KEN: I developed a lot of back pain. My primary care physician thought it was a muscle problem because I was trying to get back into exercising. I went to physical therapy, but that didn’t help. I then went to a chiropractor because the back pain was getting pretty severe. My primary care physician gave me medication for the pain. But I ended up in the hospital. They did a bone scan and found that my cancer had metastasized to the bones in my neck and back. That was in December 2001.
Do you remember what your PSA was at that time?
KEN: It had really gone up. It was over 16 ng/ml. I had to have radiation therapy again. It was a little more stressful the second time around. Radiation to the neck burned my throat, and I developed sores in my mouth. I couldn’t eat or drink. I got so dehydrated that I ended up in the hospital.
We also decided that because there was obvious disease in the bone, and because my PSA had gotten quite a bit higher, I should initiate hormone therapy. So I went on Lupron (leuprolide). The radiation and hormones combined brought my PSA down to 1.5 ng/ml.
BUBLEY: That was a nice response. And as I recall, your PSA stayed relatively low for the next year and a half. But between July and September 2003, it rose from 1.6 to 9.1 ng/ml. I gave you another Lupron shot in September, but it didn’t lower the PSA. In fact, your PSA went up to 12.8 ng/ml in October. Until then, I don’t think you had any problems with Lupron other than the fatigue, is that right?
LINDA: He had hot flashes at night. He’d break out in a sweat and wind up soaking wet. Having dealt with that myself, I said, “Welcome to the club!” (See “What causes hot flashes?” below).
KEN: Periodically, I took breaks from hormone therapy and then restarted it when the PSA began to go up.
BUBLEY: That’s right. Part of the reason for the breaks was that the hot flashes were making it hard for you to sleep. The therapy was also making you feel fatigued.
KEN: The breaks lasted about three months or until things started going astray with the PSA. But then the PSA kept going up even with the Lupron. That’s when Dr. Bubley told me that I had androgen-independent prostate cancer. So we talked about another clinical trial — this one was a phase II study on estrogen therapy. I didn’t want to go on chemotherapy, and I felt like I was running out of options, so I agreed to try Premarin (estrogen).
What causes hot flashes?
Hot flashes, similar to the ones women experience during menopause, plague some men on hormone therapy. Doctors think that shifting hormone levels affect the hypothalamus, the part of the brain that functions as the body’s thermostat.
During a hot flash, blood vessels dilate, warming the skin. This triggers sweating, which helps the body reset at a normal temperature.
BUBLEY: That made sense because estrogen blocks the signal to produce testosterone.
What kinds of conversations did you have to try to sort out the options? How did you go about making these important decisions?
KEN: Linda and I would talk about it, and we’d always be in complete harmony.
LINDA: I think that was because I went to all of the appointments. I felt that if the two of us were there, we’d pick up more information. It wasn’t one of us telling the other everything at home. Usually some options were recommended over others, and we’d ask why. We pretty much decided before we even left the doctor’s office what we were going to do, the direction we wanted to take. We also knew that if something didn’t work, we’d have other options.
BUBLEY: Well put, Linda. I think we tried to make this decision as a group. We looked around to see what else we could do, what options we had. Chemo therapy was one option, but we all felt that Ken’s quality of life would be a little better if we could delay that. So that’s when we looked at the estrogen-based therapy Premarin. What do you remember about that clinical trial? How did Premarin make you feel?
KEN: I don’t recall any side effects from it. My PSA went down as low as 0.3 ng/ml for about eight months before it started rising again in December 2004. When my PSA is rising, even a little, I know something is happening.
BUBLEY: That was when I put you on a different hormone therapy medication, Casodex (bicalutamide).
KEN: That’s right. I didn’t have any side effects from it, but I wasn’t on it that long.
BUBLEY: Six months. We didn’t get a lot of time out of it, but our goal was to see if we could delay or prevent the need for chemotherapy, so we kept trying other hormone treatments. We got a little bit of mileage out of the Casodex. Not much, but six months is better than nothing.
Then what? Chemotherapy?
BUBLEY: That’s right. I presented a clinical trial to Ken and Linda in early 2007. It involved a standard chemotherapy drug called Taxotere (docetaxel). Everyone in the trial got that drug and the drug prednisone. In addition, participants got either a placebo or a third drug, called Avastin (bevacizumab). Because Avastin affects blood vessels, researchers theorized that it might help stop the growth of cancer cells by blocking blood flow to the tumor.
KEN: Even though part of it could have been a placebo, I was willing to try it. Treatments were scheduled every three weeks.
LINDA: The problem was that after each of the first two treatments, he’d wind up getting sick within a week. He was dehydrated. Two days after the third treatment, he couldn’t even stand up. He was falling all over the floor. I thought it was the dehydration coming back, only faster. I called an ambulance. I told them he was dehydrated, but when we got to the hospital, we found out it was a lot worse than that.
KEN: I was losing blood. After several hours, they found out that there was bleeding between the small intestine and the stomach. They put about eight pints of blood in me. When I came to, I, well, I just thank God that that doctor was there to help. I almost lost my life on the table.
LINDA: It was like watching a medical show on TV. The doctor was very determined to help. He kept coming by to say that he didn’t know if anything could be done, but that he wasn’t going to give up. And he worked on Ken for five or six hours. He called in a stomach specialist, who put a camera down Ken’s throat and found a big hole in the duodenum, the first part of the small intestine.
KEN: We don’t know for certain, but I think the medication caused it. One of the warnings in the literature about the clinical trial was that it could cause major bleeding.
LINDA: We’re inclined to think that he got the third drug, not the placebo, because of the bleeding.
KEN: I’ve never had any gastrointestinal problems. Never. And now I’ve got a major bleed in my gastrointestinal tract two days after the third treatment? I think that’s the only explanation. But that’s all over. That’s all in the past now.
BUBLEY: It’s all in the past, but you almost died!
KEN: I know.
So your participation in that trial ended.
BUBLEY: There was never a question of being on the study anymore after that third cycle of chemotherapy. Like Ken, I was very concerned that the Avastin caused the bleeding. We had to file a report of the entire incident with the trial’s sponsor. We asked if they would be willing to break the code on the study so we would know for sure whether Ken was on the experimental drug or not, but they said no. To this day, I don’t know which regimen Ken got, but my suspicion is the same as his: I think he was given Avastin. He never had a stomach or intestinal problem before, and then he suddenly needed eight units of blood over a brief period of time. That was a massive bleed.
LINDA: It really was. He was in intensive care for three days, and it took six months for the hole to heal.
Did you think you received enough information about the possible risks of the treatment before you enrolled in the trial?
LINDA: Oh, yes. We had all the papers, and we read them over and over and over. We were very well informed. It was just one of those things you have to debate. You can’t do nothing. You have to do something, and this looked like it might be an effective treatment. Yes, it was a trial, but trials often work.
KEN: I agree. Anything you read related to any type of trial indicates that death may be involved. Sure, that makes you open your eyes a little bit more than usual. It makes you a little bit hesitant. But you have to be willing to take a risk to find a cure, and that’s what I did. They really emphasized that these kinds of problems can happen, so if I was terribly afraid, I wouldn’t have even pursued the treatment. But I wanted to take the treatment in the hope that it would work for me and others.
What’s happened since then? Have you tried other types of chemotherapy?
KEN: Last November, I was having lots of pain in my lower back and trouble walking — I fell down a couple of times. We went to the emergency room and, come to find out, there was a tumor growing in my spine that was affecting the nerves in my legs. I had already had radiation to that area, so surgery was out. Instead, I had radiation treatments with CyberKnife. This device delivers radiation very precisely, so the radiologists could target the areas in question and avoid the areas that had been treated years ago. And I only needed about three treatments, compared with the regular radiation, which would require about 30 treatments.
I didn’t get dramatically better — I still have difficulty walking — but the radiation stopped the progression of the tumor in that area, so I’m not getting any worse.
BUBLEY: Ken’s PSA went down a little bit with the radiation, but by January 2008, it had climbed to 16.3 ng/ml. That’s when we started another type of chemotherapy called mitoxantrone (Novantrone).
KEN: It’s been a lot better than my prior experiences with chemotherapy. Very few side effects — nausea for a couple of hours, but that’s it. And I’ve been having good luck with it in terms of bringing down my PSA.
BUBLEY: After four treatments, it’s down to 6.2 ng/ml. If we can keep the PSA going down, or at least not going up, maybe we’ll slow or prevent the progression of the disease in the bone.
How are you coping with all this after 13 years?
KEN: It’s difficult. It’s hard to find the sunshine sometimes. But you have to play the cards you’ve been dealt as best as you can and get the best treatment that you possibly can. So far, it’s kept me alive for 13 years.
BUBLEY: It almost killed you, too.
KEN: Yes, that’s true. But you know, that’s the only way any advancement and any new treatments are going to happen. There really isn’t a cure for prostate cancer now, and the only way doctors and scientists will find one is if people participate in trials. (See “Is a clinical trial right for you? below.)
Is a clinical trial right for you?
While clinical trials directly benefit thousands of people every year, they aren’t without risks. Before you enroll in one, get as much information about it as you can. Ask the research team questions such as these:
- Why is the study being done?
- Have other studies evaluated this drug or procedure? If so, what were the findings?
- Is there a chance that I will receive a placebo?
- What are the possible risks and benefits of participating?
- What other treatment options do I have?
- What treatments, tests, and medical procedures will study participants receive?
- Can I continue to take my regular medications?
- How long will the study last?
- Will I have to pay for any treatments or tests? If so, how much will that cost?
- If I need additional medical care as a result of participating, will my insurance company cover it?
- If the investigational drug or treatment works for me, can I continue to receive it when the trial ends?
- Who will be responsible for my care?
- How might my participation affect my daily routine? Will I need to miss work? Does the study involve a hospital stay?
Originally published July 1, 2008; last reviewed April 22, 2011.