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Patients Speak: Getting Chemotherapy

Bill R. found out he had prostate cancer about a year and a half ago. He’s been on Taxotere (docetaxel) and has just started Jevtana (cabazitaxel).

He spoke with Prostatepedia at length about his experiences with chemotherapy for prostate cancer. How did you find out that you had prostate cancer?

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Bill R.: We had just moved from California to Arizona for my retirement when I was diagnosed. I got to the point where I couldn’t pee, so I ended up at the urologist. After a bunch of tests, the urologist said, “You’ve got an enlarged prostate. You can either run around with a bag of pee tied to your leg for the rest ofyour life, or we can do a transurethral resection of the prostate (TURP) to cut part of it out.” They did the TURP, and they biopsied it.

That’s when they called me with the bad news. I had Stage IV prostate cancer that had metastasized. It was well along. It’s not been a year and a half.

What was your reaction?

Bill R: It was a surprise, certainly not expected. It takes a while to internalize it, and the first question you ask is: how long have I got? That’s like asking how to push a piece of string uphill. Nobody really knows the answer. They said that it’s very aggressive and, without treatment, probably two years or less.

What kinds of treatment did you have?

Bill R: Everything happened almost immediately because they said it was aggressive, and I couldn’t screw around. I was on androgen deprivation therapy (ADT): Lupron (leuprolide), which suppresses the testosterone, and Xgeva (denosumab). At the same time, I started chemo because the protocols at that time said the two of these together seemed to extend life.

Which chemo drug did you go on?

Bill R: Taxotere (docetaxel).

What was that like?

Bill R: Initially, I was in pretty good shape, and once I got diagnosed, I worked out even harder. I was swimming half a mile per day and more. I figured I had the strength in my body to get through this. Through the first three or four treatments of chemo, I had some of the usual effects, like constipation, occasional nausea, and stuff like that. I took a probiotic during treatment. That seemed to help. Other than that, I really didn’t have much of a problem, although, each chemo session beats you further down into the dirt. It’s once every three weeks, so you get weaker as you go through it.

Right, of course.

Bill R: They were going to do six chemo sessions, but my PSA just would not come down. They had expected it to drop close to zero, and we got down in the 20s, but that’s about where it ended up. They wanted to do two more chemo sessions, and I agreed to that. At that time, I had six chemo sessions, and the last two were pretty hard. It really did wipe me out in terms of energy and everything else. I didn’t have a lot of reaction to it, though.

I had a moustache that got so thin, I just shaved it off. The hair on my head thinned, but I didn’t lose all of it. It got very sparse, and I had little bald spots, but it was short and fuzzy. It all grew back differently. I now have a bunch of cowlicks, where before, I had nice straight hair. Chemo usually causes the fingernails to look awful for a while, and I lost my two big toenails, but they have now grown back, more or less.

The chemo started in September 2016 and ended February 2017. After the last chemo session, my PSA was still up at around 23 or 24. They worked on getting me approved for Provenge (sipuleucel-T), which is an early immune therapy. They extract your white blood cells and send them to a lab, where they do something, and then put them back in. I did that in the summer of 2017.

Over the next several months, my PSA came down. It got to a low of about 11, but that’s as low as it ever got. There were times when the chemo was bad. In the beginning, I didn’t realize how much you had to stay hydrated.

I didn’t know that.

Bill R: Yes. They offered for me to come in a day later, and they pump you full of a liter of saline.

Were you able to keep going about your daily activities or were you incapacitated?

Bill R: It slowed me down. First of all, you don’t know what you don’t know, so you’re not really prepared for this.

Chemo causes constipation, and if you’re prepared for that, it’s not a problem; you take laxatives ahead of time. But if you don’t know that, it’s a pretty miserable couple of days. From that standpoint, it slowed me down, but it didn’t stop me from going about our daily routine.

For the first month or two, I continued to swim, though not as much as I had been. I assumed that if I stayed active it would help me through the chemo. I was never incapacitated in that sense. There were a few days where either I didn’t feel well or was really tired, so I didn’t go out and pound the pavement or anything. In retrospect, it was hard to tell in the first month or so whether the chemo or the Lupron (leuprolide) was causing more issues.

Because you were taking them simultaneously?

Bill R: Yes. You’re doing everything at the same time. I guess, in retrospect, I slowed down and had a few days of down time. But it didn’t stop me from doing what I wanted to do.

I went out and bought a custom chopper motorcycle, and after my Provenge (sipuleucel-T) treatment in the summer, I took a 3,500-mile ride up to Sturgis, out through Yellowstone, and home. Two weeks later, we spent a month in Europe. It was hard for me, but maybe it wasn’t as hard on me as it might have been on others, simply because I was in pretty good shape when I started. If you’re not in good shape, it could be tougher. They give you some steroids to help you through this, and in the beginning, it took a while to get the steroids adjusted. They gave me too much, and I got mouth sores for a while. Once the steroids got adjusted, that was fine. The worst part of the whole thing was after it was over. Inside of a week, I started to retain water. I put on 20 pounds, and it was all water. I’m not a big guy at about 150 pounds and 5’8”, but I looked like the Pillsbury Doughboy. Living in Arizona, you run around in shorts all the time, and even the cargo shorts that I wore were so tight that they’d leave marks on my legs.

Were you able to start exercising again after everything was done?

Bill R: Yes. I started swimming again and working out. When I did the Provenge (sipuleucel-T) in the summer, that wasn’t so bad, I guess. It’s something that most people don’t want to go through—let me put it that way. There were days I was extremely tired and didn’t feel well. I was able to get back on my feet, exercise, and lead a normal life.

Doing that again, with what I know now, it probably would have been less of an impact on me. That’s the challenge for a lot of people. You go into this, and you don’t know what you don’t know. The doctors don’t really know how you’re going to react to some of this either.

Right, because everybody is different.

Bill R: Exactly. They had to adjust things like the steroids, and then things were better. They expected my water retention. I had some neuropathy damage in my feet, which is permanent. When I walk around, I feel like I’m walking on water bubbles all the time, so I’m not really stable. That took a while to get used to. Staying active will make you feel better, even if it’s just going out for a walk every day, so you’re not sitting there thinking, “I’m going to die, and this is awful.”

Right. It’s not good for anyone to dwell on that.

Bill R: Right. As soon as you head down that path, you’re toast. You’ve got to find a way to live your life. It forces you to get all your affairs in order because you realize that you’re going to pass away before you expect to. I’m starting Jevtana (cabazitaxel) in a few months because the cancer has progressed.

I’ve heard people can tolerate Jevtana (cabazitaxel) a little better. The side effects are not as severe as Taxotere (docetaxel).

Bill R: That’s what they’re telling me, that I shouldn’t expect things like water retention and so on. I am going through that now, so the doses are once every three weeks for six rounds. We’ll see how that goes. But it is what it is. I tell everybody if you live long enough, you’re going to get prostate cancer.

That’s actually true.

Bill R: It’s only a question of when. If you get it like I did, earlier in life, it shortens your life. But if you get it when you’re 90, nobody knows and nobody cares. Hopefully I’ve helped people a little bit.

A lot of it is mental. If you swear that this is going to be miserable, everything you look at will contribute to that feeling. Whereas, if you’re determined to get through it with a positive attitude, it’s not as bad. There’s a lot in the mental side that really helps you get through it.

Join us to read the rest of our August conversations about chemotherapy.


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Dr. Vogelzang Offers Advice for Men Prescribed Chemo For Prostate Cancer

Dr. Vogelzang 2015Dr. Nicholas Vogelzang is a medical oncologist at Comprehensive Cancer Centers of Nevada. He is a member of the 2018 Class of Giants of Cancer Care, a designation awarded to healthcare professionals advancing the field of oncology by their contributions in research and clinical practice.

He also serves as Associate Chair for the Genitourinary Committee of US Oncology, the Vice Chair SWOG GU committee, and the Associate Editor of Kidney Cancer Journal and Clinical Genitourinary Cancer.

Prostatepedia spoke to him recently about the development of chemotherapy for prostate cancer. He also offers advice for men prescribed chemotherapy and thoughts on a new class of drugs called PARP inhibitors.

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Do you have any advice for men who have been prescribed chemotherapy? For many patients, it’s a frightening thing. There’s a cultural concept that chemotherapy is terrible.

Dr. Vogelzang: I understand how seriously patients take this issue, although it’s an unfounded fear. I have a patient who is dying. He’s a retired pilot. He refused to take chemotherapy. Yet, he went to the Philippines and spent $30,000 on some herbal potion rather than go on chemotherapy. He came back far worse than when he left. At this point, he’s trying chemotherapy, but he’s just taken too long to get it.

There are a couple of things I’d say. Number one: don’t wait too long. Take chemotherapy when you’re strong. Number two: all the side effects are reversible. You don’t suffer the whole time, although fatigue is real. You’ll have nausea for a day and some folks get bad diarrhea. We have developed dramatically effective drugs to prevent diarrhea, nausea, and vomiting. You don’t vomit anymore. You may not even get nauseated. About the only thing you get is fatigue. Taxotere (docetaxel) can cause hair loss, but Jevtana (cabazitaxel) does not.

If you use an ice cap, like women do with breast cancer, you don’t lose your hair. You can get some numbness in the fingers, but you can prevent that by using ice on your hands. There’s even a product on the market now, called the cold cap, that you can buy for $300 or so that you wear on your head. It looks like a World War I flying cap from the Red Baron. You put it on your head during the one hour of chemotherapy. It virtually prevents the hair loss.

There are also mittens and stockings that protect against fingernail and nerve damage in the hands and feet. You can do it the inexpensive way and put your hands and feet in ice. People come into my clinic and ask what all those guys are doing with their feet in ice? It’s to prevent nerve damage from the chemotherapy.

Like I said, Jevtana (cabazitaxel) avoids those side effects. I try to give Jevtana (cabazitaxel) whenever I can first for that reason. Usually, the insurance requires Taxotere (docetaxel) first because Jevtana (cabazitaxel) is a lot more expensive. Jevtana (cabazitaxel) can be really well tolerated for a long time. I have one patient who is a rancher originally from Minnesota. He is on dose number 27 of Jevtana (cabazitaxel). His PSA started in the high hundreds and now it’s 11. In some patients, chemotherapy is highly effective, long lasting, and is clearly not to be feared.

It’s just urban legend that somehow chemotherapy is bad. We figured out many years ago that chemotherapy is not to be feared.

Join us to read the rest of Dr. Vogelzang’s comments on chemotherapy for prostate cancer.


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Chemotherapy For Prostate Cancer

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Dr. William Oh, of the Mount Sinai Medical Center and the Icahn School of Medicine at Mount Sinai in New York City, is a medical oncologist and expert in the management of prostate, renal, bladder, and testicular cancers.

Prostatepedia spoke with him about the role chemotherapy plays in prostate cancer treatment strategies.

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What types of chemotherapy are available to prostate cancer patients today?

Dr. Oh: In many ways and for many patients, chemotherapy has a negative reputation. People tend to lump all chemotherapy drugs together, but it’s very important to remember that there are hundreds of kinds of chemotherapy. The word chemotherapy really just means chemical therapy for cancer, but that’s not the same thing for everyone.

There are two major chemotherapy agents approved and commonly used in prostate cancer: Taxotere (docetaxel) and Jevtana (cabazitaxel). When Taxotere (docetaxel) was first approved in 2004, it was really an important milestone because up until that point, there were no drugs of any kind that were proven to improve survival in metastatic prostate cancer.

Taxotere (docetaxel) showed that it could be done. Then it took many years of research and clinical trials to get to the next set of drugs that improved survival, especially in castrate-resistant prostate cancer. These include drugs like Zytiga (abiraterone), Xtandi (enzalutamide), Provenge (sipuleucel-T), and Xofigo (radium 223). Since 2004 with the approval of Taxotere (docetaxel), we still think improving survival is the most important goal for patients with advanced prostate cancer. As an oncologist, I felt the survival improvement is— for most patients–worth the side effects patients may have.

This is a critical point, because many people think that chemotherapy has terrible side effects and doesn’t do anything of value. That is not a fair stereotype. While it does have side effects, and it doesn’t always work, in many ways, chemotherapy has great value for our patients in terms of improving both their survival and their quality of life.

The perception is definitely that the side effects of chemotherapy can be terrible, so how might chemotherapy improve quality of life?

Dr. Oh: When we first started giving chemotherapy for metastatic disease (and still today), patients were often very symptomatic. They had a very short expected lifespan, and they were in pain. They were weak. They couldn’t walk. They would have a lot of side effects from cancer. The way that drugs like chemotherapy can boost quality of life is that, by shrinking the cancer—by directly killing cancer cells, we can make patients feel better. If they have fatigue or some hair loss from chemotherapy, that wasn’t something they wanted, but they could be in a much worse state from the cancer itself. They were really suffering from it.

In balance, the chemotherapy was able to make them feel better by reducing their pain medication requirements and by improving their functionality and their appetite. We often see that. When chemotherapy works—and it’s not always—it can really shift a person’s quality of life, and it also improves their duration of life. These are the two critical factors for any cancer drug.

When is a patient likely to encounter Taxotere (docetaxel) and Jevtana (cabazitaxel)? Why would your doctor choose one over the other?

Dr. Oh: When docetaxel was first approved, it was approved for metastatic castrate-resistant prostate cancer (CRPC).

In that state, it had a relatively modest survival benefit on average. But for individual patients, it could have a dramatic benefit. We always thought, why wait till the patients develop CRPC? If we use it earlier, would it have a greater impact?

In 2015, the CHAARTED and STAMPEDE studies showed that early use of Taxotere (docetaxel) chemotherapy in men with newly diagnosed metastatic disease could have a very profound improvement on survival. In other words, rather than waiting for the cancers to become resistant to hormone treatments, if you used hormones with chemotherapy right up front—six cycles of Taxotere (docetaxel)—you could have a more dramatic improvement in overall survival.

That changed the standard of care for how we use Taxotere (docetaxel) chemotherapy. Now it’s an optionfor patients when they’re newly diagnosed with metastatic disease. Jevtana (cabazitaxel) was approved in 2010 based on the TROPIC study in patients who had already received first-line Taxotere (docetaxel). Jevtana (cabazitaxel) is currently a second-line chemotherapy agent. It does have a different set of side effects compared to Taxotere (docetaxel). For example, patients are less likely to lose their hair. It is in the same drug class as Taxotere (docetaxel); in other words, it’s a taxane chemotherapy and works by inhibiting the microtubules that allow cancer cells to grow rapidly. Jevtana (cabazitaxel) was approved because, even in patients who had already received Taxotere (docetaxel), Jevtana (cabazitaxel) improves survival and may be an important second chemotherapy for patients to receive after they’ve already received Taxotere (docetaxel).

Are these drugs ever used in combination with something else?

Dr. Oh: Generally, chemotherapy is not used in combination with other drugs because usually these drugs are given in sequence. Whether this is the correct way to do it or not is not 100 percent clear. There are ongoing research studies to see if they can be combined safely rather than given in sequence because they may have an additive or synergistic benefit if you combine, for example, a chemotherapy drug with an androgen-receptor targeted therapy or with a bone-targeted therapy.

As in Erleada (apalutamide) or Xtandi (enzalutamide)?

Dr. Oh: Exactly.

What should men know if they’ve been prescribed one of these drugs?

Dr. Oh: Try not to have an uninformed ‘gut reaction’ to chemotherapy, especially if you think automatically it’s not the right treatment. We know that chemotherapy may be less targeted than other drugs, but cancer cells are tricky and they often learn how to mutate and change. Chemotherapy can knock out many different kinds of cancer cells. That may be one of its advantages. It works differently than androgen-receptor therapy, immunotherapy, and bone therapy. Men should understand that chemotherapy is a very important option, especially when the cancer has become more aggressive.

Join us to read the rest of Dr. Oh’s comments on chemotherapy for prostate cancer.


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Mark Slaughter: My Prostate Cancer Story

DSCN7750 (ed) Denise & Mark

Mark Slaughter And His Wife Denise

The “C” word. No one can imagine the horror of being told you have cancer.

My problems began with urinary troubles: middle of the night urges, frequency, and the inability to go, start, or finish a urine stream. My primary care physician recommended a urologist.

My urologist was awesome and earned my confidence and trust with his approach. He explained he was trying to see a picture rather like a jigsaw puzzle, but in order to see the picture clearly, he needed more pieces of the puzzle. He convinced me to let him do a digital rectal exam (DRE).

The result was not good. On a 0-10 scale, 0-5 would indicate no problems and 5-10 would range from concern to panic. He said mine was about a 7 or 8. Very smooth everywhere, no evil nodules or lumps, but way too hard. Unlike the softer part of your thumb near the palm of your hand (like it should be), it felt like the harder area of your thumb where the bone is located. It was definitely a reason for concern.

Next, he talked me into a PSA test. I was one of the men who, about eight or nine years ago, read the controversial studies about PSA tests and unreliable results, and I took them to heart. Many organizations were saying PSA was overrated and shouldn’t even be used. So, I had stopped letting doctors test for mine. Now, my blood was tested for PSA and the result was bad, very bad. It was 259 (four is the top end of what is considered acceptable). To see more of the picture, my doctor wanted to do a biopsy. He respectfully listened to all of my logical arguments.

No number of needle probes will show you enough of the prostate. Too many and you can damage a fragile little organ. Besides, you would have to access a sterile body part by going in through a sewer (the rectum). He held his ground and said he really needed this important piece of the puzzle. My wife and I thought about it overnight and agreed to let him do the biopsy.

My biopsy procedure was a piece of cake. I was given an antibiotic before the procedure. An ultrasound device accurately guided the doctor, and he was able to get 12 samples: 6 from each side of the prostate. Of the 12, I was really only hurt by one of them. Each felt like someone quickly poked me with a sharp pencil. I heard the device click. I required no pain medication and passed a little blood during urination for a few days afterwards.

Then the results came. The Gleason grading system is used to evaluate the samples taken during a biopsy. A Gleason score is 1 through 10, where 1 to 5 is clear, and 6 to 10 indicates positive results for cancer. The percentage of each sample that is found to be cancerous also indicates whether the disease has spread beyond the prostate gland.

Of the 12 needle biopsy locations, nine were found to contain high percentages of cancer. Of those nine, eight had a Gleason score of 8, and the last one was scored at 7. These scores indicated the cancer had already spread into my body, beyond the prostate. My doctor said that the next step was to get computerized tomography (CT) images and bone scans that, together, would show us where the cancer had spread. The scans were performed in the hospital as an out-patient.

For the CT scan, I laid on a conveyor that moved me through a tunnel like machine. It rotated around me and took X-rays from multiple positions. A computer then combined the images into cross-section images of my body. The bone scan was a nuclear imaging procedure in which tiny radioactive tracers were injected into a vein. Then, I laid on a conveyor similar to the CT scan and the machine could view the tracers and obtain images. Various parts of my body absorb the tracers in differing degrees. Areas in my organs and skeleton with higher absorption would show up in the images as bright spots indicating abnormalities caused by the cancer.

The procedures were simple and easy enough. The results were another story.

February 8, 2018 is a day emblazoned in my memory, a day I will never forget, the day time stopped. That was the day I was told I have the big “C” word. I have cancer.

My urologist was tactful but did not mince words. The CT scan showed cancer in my lymph nodes, in my groin, and up my back on both sides of my spine. The bone scan showed lesions in four places on my pelvis and six places on my ribs. The tests all showed that I have advanced stage IV metastatic prostate cancer. He said there is no cure. But, we can manage it with hormone treatments and chemotherapy. With no treatment, I might only have a couple of years to live. With treatments, perhaps three to five years.

Upon hearing this news, my first thought was, I am dead. I had been standing next to my wife Denise, who was seated at her desk as we listened on the speakerphone. I collapsed into a seated position on the floor and reached out to catch Denise as she fell out of her chair. We crumbled to the floor together, sobbing and wailing with wrenching heaves of our chests. Squeezing each other as though life had ended that very moment. We embraced. We cried. We cried. We cried. Time stopped.

We laid together in a heap on the floor for a long time. By the time we climbed to our feet, we could hardly breathe. My face hurt from all the tears. Our eyes were swollen, our faces red below our eyes and otherwise colorless as though life itself had drained from our faces. It was like our lives were over.

My urologist referred us to an oncologist. We couldn’t stand him. He was rude and dismissive as he explained the chemo treatment plan and the poor prognosis for the remainder of my life. It is an understatement to say that he lacked a good bedside manner. Several friends immediately recommended we get a second opinion.

A friend of mine, and my former primary care physician when we lived in Atlanta, told me to forget that guy and get myself to the Winship Cancer Institute at Emory University. I did just that. At Emory I found an incredible oncologist who was instrumental in the CHAARTED study that showed excellent results of early hormone therapy combined with chemotherapy for the treatment of advanced metastatic prostate cancer.

My first appointment with this doctor was an education in prostate cancer. He explained the course of the disease, different methods of treatments, and answered each and every question I had. He described the treatment options as the tools in his toolbox. Whenever one might fail to produce results, he would reach for another one. He explained new chemo drugs, such as Zytiga (abiraterone acetate) which is administered orally, and he explained chemotherapy using docetaxel infusions. Some people prefer chemo infusions because it is six treatments and you are done. Other people would rather take pills daily for the rest of their lives. No study had been done that showed any real difference in the outcome of chemotherapy infusions versus the new chemo drugs.

At first, I was going to go the pill route. I was terrified of chemotherapy because of my preconceived notions and the horror stories from people I had known who went through chemo infusions and suffered horrendous side effects before dying painful deaths.

But there was a major snag in my getting approval for the new pill form of Zytiga (abiraterone acetate). Because I am on Medicare and have the Part D drug coverage, I was not eligible for any financial aid from the pharmaceutical companies or from any other charitable organizations for this new drug. Consequently, it was going to cost me in the neighborhood of $5,000 per month for the rest of my life. This was a huge blow to overcome mentally and financially. There was no way I could afford that.

My oncologist reassured me again that the results of chemotherapy infusions are as positive as those from the new drug Zytiga. Medicare would pay for the chemotherapy infusions. Because of these two considerations, I chose to take the chemotherapy infusions. Believe me, nothing about taking chemotherapy infusions came close to the fear and angst of anticipating it.

I have now completed all six required cycles of chemotherapy infusions with Taxotere (docetaxel). Each cycle took three weeks. The biggest side effect for me was the infamous cancer fatigue, especially during the first week after each infusion. It would take about all the energy I had to walk from my chair to my bed for a nap. My ability to concentrate was affected, too. Sometimes I had to think very hard about words or especially about sequential steps required to do something. This is a phenomenon called “brain fog.” Cramps in my ankles and legs were also problems at times.

My oncologist prescribed Compazine (prochlorperazine) to prevent nausea during the cycles and it worked extremely well for me. I also took Prednisone, a corticosteroid to suppress my immune system and reduce the negative side effects of the Taxotere (docetaxel). The Prednisone affected my mood and appetite, but I had no swelling or weight gain.

The routine at each treatment was: a lab test for blood markers, doctor appointment, then chemo infusion. If my blood looked good, the doctor approved the chemo infusion, then the Taxotere (docetaxel) was prepared and administered. The positive results were immediate. After the first infusion my PSA dropped from 259 to 20, then to 5 after the next infusion, then to 2, then 1.7, 0.83, and finally down to 0.55. Similarly, my testosterone level dropped from around 500 to less than 20, which the doctors consider insignificant. They tell me my testosterone level is that of a prepubescent boy.

One thing I did not have at all was neuropathy in my feet or hands. My wife read about studies done in Canada, the United Kingdom, and France that indicate icing of the fingers and toes during chemotherapy infusions prevents any changes to fingernails and toenails as well as preventing neuropathy.

I asked my oncologist and he said although there are no definitive studies in the United States that show results, he didn’t object to my doing it. My wife has faithfully kept my hands and feet iced during treatments. It was not pleasant, but it was certainly tolerable and gave me a big pay-off. To me, it was like a kid playing in the snow with no mittens. Each of my chemotherapy infusion sessions lasted about one and a half to two hours. Once in a while, when my hands or feet got too cold, I took them out of the ice for a short break. At the end of all six treatments, I had no changes in my fingernails or toenails and no neuropathy.

Another side effect of the chemotherapy infusions was hair loss. I had heavy, patchy hair loss on my head that started about 13 days after my first infusion. The afternoon when large patches of hair began falling out into my hands in the shower, I decided to take action. The next morning, slowly, deliberately, I dressed, collected my wallet and keys, walked to the garage, got in the car, drove to the nearest barber and got a buzz cut. I didn’t think about it. I just did it. And it was one of the best decisions I have made. It was far easier to manage quarter inch long hair than patches of messy hair. I would say to any guy, wait and see if your hair begins to fall out, then just accept the fact and manage it. I’ve also lost about three fourths of my body hair.

My hormone therapy started with Firmagon (degarelix) because it does not cause flairs or spikes in the bone lesions. Some other hormones do. After a few weeks the oncologist changed my hormone to Lupron (leuprolide). These hormones are effectively medical castration. The prostate cancer feeds on testosterone and by significantly reducing the amount of testosterone, they deprive the cancer of food. The hormones have caused me to have some hot flashes, similar to what women experience in menopause. Sometimes I have night sweats.

As for sexual function, I am 66 years old and have suffered from erectile dysfunction for six or seven years from a history of high blood pressure, type II diabetes and prostate issues, including prostatitis. One of the results of hormone therapy has been the loss of sexual function and even a reduction in the size of my genitals. I rarely have any kind of erection, although I still have the same physical feelings associated with sexual arousal.

But, with a loving partner, these things have not been so hard to accept. I still have the good feelings two people share in intimacy. I would rather be alive than fully-functional, sexually. I do admit my history has made this easier to accept than it might be for some younger men. The key here is perspective. Some choices in life are just hard. You have to decide what matters the most.

Overall, my cancer treatments and the associated side effects have been far less of an ordeal that the initial fear of treatment.

The biggest positive about chemotherapy infusion treatment is that you do it and it’s over forever. For me, I have now completed the whole course of chemotherapy and will never have to do it again. Compare this to a lifetime of multiple pills on a daily basis, worrying all the while about how long they might be effective.

On the down side, you have to get your head around walking into a room feeling good and letting them inject you with strong chemicals that will make you feel bad. It’s rather bizarre. I live about 200 miles from my cancer treatment center, so the car trip and hotel stay gave me way too much time to let bad thoughts get in the way before each treatment. Again, it’s all about controlling your thoughts and attitude. I know it sounds trite, but holding onto a positive attitude really matters.

I have a wonderful support group. First, my loving wife of 46 years is a registered nurse and the best advocate anyone could ever ask for. Second, I live in an active adult community of residents over 55. So many of my neighbors have been supportive and shared their own experiences with cancer. Third, I have a strong faith. My church friends have been amazing with calls, cards, food, gifts, and time for visits. It has been humbling to see how many dear friends I have and how supportive they are in my time of need. I think this is one of the biggest keys in getting through cancer.

I also have to mention some of the person-to-person connections I have been provided with through Us TOO that have helped greatly with good information and support.

My advice to anyone facing chemotherapy is to first go to the nearest national cancer institute (NCI). There are 70 NCI-designated cancer centers located in 36 states and the District of Columbia. These centers are the backbone of research, clinical trials for the newest treatments, and clinical care for cancer patients. Here you can then find an oncologist who specializes in your particular cancer. Ask questions, listen to suggestions, and make a shared decision with your oncologist and caregiver about what treatment you will get.

Each person’s cancer is unique and your responses to drugs will also be unique. So, ask your oncology pharmacy specialist about any drugs to be used and their most common side effects.

The Grim Reaper follows us all. Most of our lives we ignore the inevitable fact that everyone will die. But, when you receive the diagnosis of a non-curable, chronic, and ultimately terminal disease, the Grim Reaper comes up closer behind you. The key to survival is to never look back. Focus forward. Look to the light of day. Focus on the here and now. Enjoy life.

In a strange way, having advanced stage IV metastatic prostate cancer is a gift. It has changed the focus of my life in positive ways. Because now, more than ever before, I live in the present. And life is more intense, fuller, and more complete than I could have ever imagined.

Mark Slaughter © August 8, 2018


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Switching from One Chemo Drug to Another

Dr. Emmanuel Antonarakis is an Associate Professor of Oncology and Urology at the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center.

Prostatepedia spoke with him recently about his work on the benefit of switching men from Taxotere (docetaxel) to Jevtana (cabazitaxel)— or vice versa—if his PSA doesn’t go down by 30% in the first twelve weeks of treatment.

You’ve published a paper on switching patients from Taxotere (docetaxel) to Jevtana (cabazitaxel) and vice versa. What is the thinking behind switching chemotherapeutic agents? Why would you want to switch agents earlier as opposed to when the first chemotherapy drug stops working?

Dr. Emmanuel Antonarakis: The motivation behind this paper was that the FDA-approved recommended dosing schedule for both Taxotere (docetaxel) and Jevtana (cabazitaxel) is a course of ten doses, given three weeks apart. When patients begin FDA-approved Taxotere (docetaxel) or FDA approved Jevtana (cabazitaxel), they’re often told by their oncologists that they should expect to receive this chemotherapy once every three weeks for up to ten doses. A patient may not receive ten doses or might stop the therapy before he reaches ten doses because he cannot tolerate the therapy and has unmanageable side effects, or his cancer begins to progress before he ever get to dose number ten. If his PSA begins to increase again at dose six or seven or the tumors begin to grow again, his oncologist might ask him to stop chemotherapy.

We then wondered whether the ten doses was a reasonable time to wait or whether there could be an early indicator, or an early sign, of therapy resistance or therapy futility without having to go through six, seven, eight, nine or ten doses.

The idea that we had was to test an early intermediate marker of sensitivity or resistance to the chemotherapy. The best marker of early sensitivity or resistance that we could think of was whether or not a patient had a 30% PSA drop within the first four cycles of therapy. As you recall, if the therapy is given once every three weeks, four cycles basically means 12 weeks, which roughly equates to about three months.

The decision to use this intermediate endpoint was not arbitrary; it was based on some large retrospective meta-analyses that have shown that the strongest predictor of overall survival in patients receiving both Taxotere (docetaxel) and also separately Jevtana (cabazitaxel) was whether or not patients had a 30% PSA reduction after 12 weeks.

Patients who do achieve at least a 30% or greater reduction in the first 12 weeks have a survival that’s longer than patients who don’t achieve that endpoint. We thought, well if this endpoint is strongly correlated to survival, perhaps we can use it as a decision point. If after four doses of therapy or 12 weeks of therapy a patient don’t achieve a 30% reduction in PSA perhaps we should switch him to the other chemotherapy, rather than sticking with it and just waiting for either the toxicity to develop or the PSA or the radiographic disease to progress. That was the hypothesis.

We designed a relatively small study of about 63 patients. We used a 2:1 randomization so they were twice as likely to get Taxotere (docetaxel) compared to Jevtana (cabazitaxel). Approximately 41 patients got Taxotere (docetaxel) first. The other 22 patients, got Jevtana (cabazitaxel) first. Irrespective of which arm they were randomized to, they received the first four doses of chemotherapy in 12 weeks. We checked their PSA every three weeks.

At the end of the fourth dose, if the PSA level had dropped by 30% or more, the patients would continue on the same therapy on which they started. However, if patients did not achieve a 30% reduction or more, they would be switched to the other chemotherapeutic agent.

If a patient had a 25% reduction, we would switch him to the other agent because we thought that was not good enough. If someone received Taxotere (docetaxel), and their PSA dropped by 25%, even though it dropped by 25%, it did not meet that 30% threshold so they would then switch for the fifth dose to receive Jevtana (cabazitaxel) for the remainder of their chemotherapy. The inverse was also true. If the patient received Jevtana (cabazitaxel) first and also did not get a 30% reduction by week 12, in other words four doses, they would also switch to receive Taxotere (docetaxel). The interesting thing that we found in both treatment arms was that the chance that a patient had a favorable PSA response, which was defined as a 50% or more decrease, was higher than we had seen in historical trials using each drug by itself without switching. To put some numbers on that, we found that there was about a 54% chance that patients would have a 50% reduction in PSA if they had to the opportunity to switch from one chemotherapy to the other, compared to about a 45% chance of PSA reduction in the historical data where patients did not switch.

Did it matter if they got Jevtana (cabazitaxel) first or Taxotere (docetaxel) first?

Dr. Antonarakis: What we found out is a bit of a paradox: people could benefit from the switch in both down over time and the availability of non-chemotherapy agents is going up. A lot of these patients who may not have a 30% PSA reduction with one chemotherapy, might choose to do another hormone therapy, a radiopharmaceutical drug like Xofigo (radium-223), immunotherapy like Provenge (sipuleucel-T), or even a PD-1 inhibitor, or potentially a PARP inhibitor.

It might be difficult to convince a patient who has just failed one chemotherapy after four doses to go immediately to a second chemotherapy. I’m not 100% sure what the future will hold. I also don’t think this is a trial that we could have conducted today.

What would you say to a man reading it? That this is worth talking to his oncologist about or is this just something interesting for him to know about?

Dr. Antonarakis: Patients who are beginning their first chemotherapy should discuss this trial with their oncologist, and together with the oncologist decide in a joint fashion whether switching from one chemotherapy agent to another after four doses might be right for him, especially if he’s tolerating the chemotherapy well. If he tolerates the drug and his PSA has not dropped by 30% or is continuing to increase, then in my opinion rather than continue with the potentially futile therapy, a patient and his oncologist may wish to consider using this trial to guide or justify their choice of switching drugs earlier rather than later. directions. That was fascinating to us because, as we all know

Jevtana (cabazitaxel) was specifically approved by the FDA as a second-line curative therapy only indicated in men who have failed Taxotere (docetaxel) first. Based on that reasoning, one might expect Jevtana (cabazitaxel) to work better after Taxotere (docetaxel) but not Taxotere (docetaxel) after Jevtana (cabazitaxel).

This is not what we found.

We found that in both directions, both from the Taxotere (docetaxel) to Jevtana (cabazitaxel) switch, but also in the Jevtana (cabazitaxel) to Taxotere (docetaxel) switch, there was a significant amount of patients, approximately half, who were salvaged by the crossover therapy. By salvaged, I mean those who did not achieve a 30% PSA reduction with the first drug but did achieve a PSA reduction of 50% or more after crossing over to the second drug.

As I mentioned before, this occurred in both directions, both in patients receiving Jevtana (cabazitaxel) after Taxotere (docetaxel) and Taxotere (docetaxel) after Jevtana (cabazitaxel).

Are the side effects of Jevtana (cabazitaxel) a little bit easier to take than the side effects of Taxotere (docetaxel)?

Dr. Antonarakis: Interestingly, the side effects of Jevtana (cabazitaxel) in the published literature indeed appear to be slightly better. In this particular trial, which was very small obviously, they seemed comparable. In other words, we did not see any appreciable difference between the Taxotere (docetaxel) and the Jevtana (cabazitaxel) overall in terms of side effects. Taxotere (docetaxel) had a little bit more neuropathy nerve damage, which Jevtana (cabazitaxel) did not do. On the other hand, Jevtana (cabazitaxel) had a little bit more neutropenia, while the Taxotere (docetaxel) did not.

I would say that when patients receive these agents in a first-line setting, in other words, when they had not received another chemotherapy previously, their side effects were fairly comparable. I don’t think there was a clear signal in terms of one drug being clearly safer than the other.

Does it matter which you get first?

Dr. Antonarakis: From a side effect perspective, they’re both fairly equivalent in terms of tolerability, with slight differences in neutropenia, which is worse with Jevtana (cabazitaxel) and neuropathy, which is worse with Taxotere (docetaxel).

What is the next step? Are you going to run a similar trial with more patients?

Dr. Antonarakis: One question that arises is if this small randomized trial is enough to change practice. Should a community oncologist or urologist give Taxotere (docetaxel) for four doses and wait to see if the patient’s PSA drops by 30% or more? If it doesn’t drop to 30% or more, should he to switch to Jevtana (cabazitaxel)?

I have to admit that this is something that I have done in my practice a few times, but I really don’t believe that this is ready for clinical practice yet. Yes, in this trial, we showed that the PSA response rates could potentially be improved by this switch strategy. What we did not demonstrate was whether this improves overall survival.

The ultimate question is does switching chemotherapy agents after four doses improve survival, compared to just waiting until we see radiographic or clinical progression to switch agents. That would, as you mentioned, require a larger Phase III randomized study. The idea of study design would be to randomize patients to the switch strategy versus no-switch. We would randomize one group of patients to receive chemotherapy and switch if their PSA did not drop by 30%. The second group of patients would start chemotherapy but would not be given the opportunity to switch, even if their PSA did not drop by 30% or more. The randomization would not necessarily be the randomization to the chemotherapy, but would be randomization to a switch strategy versus a stick-with the first-chemotherapy strategy.

Sanofi, which makes both Jevtana (cabazitaxel) and Taxotere (docetaxel), have not been eager eager to respond to such a study because of financial considerations and also because the patent life of Taxotere (docetaxel) is over and the patent life of Jevtana (cabazitaxel) will be expiring soon.

Unfortunately, we might be left with a Phase II study that may, potentially, not translate into a Phase III study. I think individual patients and individual oncologists may look at these data and might be convinced that some patients might potentially benefit from a switch strategy, especially those who did not have any degree of PSA reduction after four cycles.

An added complexity is that the popularity of chemotherapy is going down over time and the availability of non-chemotherapy agents is going up. A lot of these patients who may not have a 30% PSA reduction with one chemotherapy, might choose to do another hormone therapy, a radiopharmaceutical drug like Xofigo (radium-223), immunotherapy like Provenge (sipuleucel-T), or even a PD-1 inhibitor, or potentially a PARP inhibitor.

It might be difficult to convince a patient who has just failed one chemotherapy after four doses to go immediately to a second chemotherapy. I’m not 100% sure what the future will hold. I also don’t think this is a trial that we could have conducted today.

What would you say to a man reading it? That this is worth talking to his oncologist about or is this just something interesting for him to know about?

Dr. Antonarakis: Patients who are beginning their first chemotherapy should discuss this trial with their oncologist, and together with the oncologist decide in a joint fashion whether switching from one chemotherapy agent to another after four doses might be right for him, especially if he’s tolerating the chemotherapy well. If he tolerates the drug and his PSA has not dropped by 30% or is continuing to increase, then in my opinion rather than continue with the potentially futile therapy, a patient and his oncologist may wish to consider using this trial to guide or justify their choice of switching drugs earlier rather than later.

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Managing Chemotherapy Side Effects

Dr. Cy Stein is a medical oncologist at California’s City of Hope hospital. He routinely advises his fellow doctors to, “Never think about yourself. It’s only about the patient.”

Prostatepedia spoke with him about dealing with the side effects of chemotherapy for prostate cancer. Why did you become a doctor? What was it about medicine that drew you in? What keeps you there?

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What are the most common chemotherapy drugs that men with prostate cancer are likely to encounter today?

Dr. Cy Stein: It all depends on what your definition of chemo is, but I take a very narrow definition that I think most of the community would take. There are two chemotherapy drugs that exist for prostate cancer. One of them is called Taxotere (docetaxel). The other is Jevtana (cabazitaxel). I don’t consider drugs like Lupron (leuprolide) to be chemotherapeutic agents. We consider them to be hormonal agents because they act directly on testosterone. Testosterone, as I’m sure everybody knows, is the male sex hormone. In order to get responses in prostate cancer, physicians have to lower the patient’s level of testosterone in their blood. That’s not a chemotherapeutic way of doing it; that’s a hormonal way of doing it.

Similarly, the newer drugs that have come out recently are not chemotherapeutic agents either. I’m referring to Zytiga (abiraterone) and Xtandi (enzalutamide). We call them oral hormonals. Provenge (sipuleucel-T) is a kind of tumor vaccine, so it’s really immunologic oncology. Xofigo (radium 223) is also not a chemotherapeutic agent, so we’re down to two.

What are the differences between the two. When would Taxotere (docetaxel) be used over Jevtana (cabazitaxel)?

Dr. Stein: Taxotere (docetaxel) was first developed in 1995-1996 and has been on the market for a long time. It was originally used in breast cancer and lung cancer as well. Then it was introduced for use in prostate cancer.

There is significant amount of toxicity with Taxotere (docetaxel), although it is a very good drug. It is different from Jevtana (cabazitaxel), even though both of the drugs are formed to the same general class of molecule, which we call taxanes. They both come from, ultimately, the needles of the Pacific Yew tree. Even though the names sound similar, these are different drugs with different toxicity profiles.

The important thing for a patient to remember is that, even though these drugs have side effects, at times we see spectacular responses from both of them. The side effects are manageable and definitely worth the effort for the patient because of the potential for the response that you can get. Taxotere (docetaxel) has more side effects than Jevtana (cabazitaxel). Taxotere (docetaxel) seems to have more toxicity, and most important, the toxicity seems to get worse as patients age. Therefore, I find it extremely difficult, if not impossible, to give Taxotere (docetaxel) to men who are over 80.

What toxicities are we talking about?

Dr. Stein: For Taxotere (docetaxel), the major dose-liming toxicity is fatigue. People are not going to feel anything on the day that they get the Taxotere (docetaxel). The day after, they’re going to feel pretty tired, and most men will want to just stay in bed. Their partners don’t particularly like that, but it’s probably best to leave them in bed because they’re not going to be very functional for a day or more on Taxotere (docetaxel).

It’s not uncommon for a man to say, “For three days after I get this drug, I’m very wiped out.” I’ve even heard them say, “Five to seven days after I get this drug, I feel very wiped out.” Then the men will get better, and eventually they will come back for their next cycle, and we’ll do it all over again. It doesn’t happen quite so much with Jevtana (cabazitaxel) because it is a little easier on the fatigue.

In terms of other side effects, one of the side effects that Taxotere (docetaxel) has, only in about 10% of cases, is febrile neutropenia. That is the white blood cell count goes down seven to nine days after getting the chemotherapeutic drugs and leads to an infection. The patient will have a fever of 100.4 or greater, and the febrile neutropenia requires antibiotics. With Jevtana (cabazitaxel), the incidence of febrile neutropenia is much, much higher. What I do is I make sure that all of my patients have Neulasta (pegfilgrastim) applied before they get the chemotherapy, to prevent their white count from going down.

There are some patients who may not need Neulasta (pegfilgrastim), but I prefer to sleep calmly at night. I don’t want to worry about a patient getting febrile neutropenia on Jevtana (cabazitaxel), so I treat every one of my patients with Neulasta (pegfilgrastim).

In terms of other toxicities, many men say that Taxotere (docetaxel) also causes food to taste like cardboard. Their hair will certainly thin, but it probably won’t all fall out. They may get tearing of the eyes. They may get changes in their nails such as brown bands that horizontally cross the nails. These disappear after discontinuation of treatment. They can also, potentially, get a little bit of fluid in their lungs, although in my experience that hasn’t been a clinical problem. They can also, potentially, develop neuropathy.

It sounds rough, and for some men it is, but a lot of men go through it very well. They can have a tremendous response. I’ve seen any number of individuals have responses of 75% and even 90% in their PSA. These are the kind of individuals who live a great deal longer than if they didn’t respond.

Jevtana (cabazitaxel) is a very similar story, except the fatigue is much less. The neuropathy is significantly less, although I have seen patients with neuropathy on Jevtana (cabazitaxel). The nail banding does not happen. The poor taste doesn’t happen. The hair loss is greatly reduced. Fatigue is also significantly reduced, but there is still fatigue in some patients.

Because the toxicity profile is better with Jevtana (cabazitaxel), I don’t hesitate giving this drug to patients who are over 80 years old. In my opinion, they seem to tolerate it better. I had a patient who was 90 years old and of sound mind and body. He didn’t have much of a choice; he had two sons who were doctors. We talked it over and he said, “I want the drug.” He got the drug, and I started him with a much lower dose than the full recommended dose. I titrated him up to tolerability, and he received 13 consecutive cycles of Jevtana (cabazitaxel). All his pain went away, and he lived an extra year.

Jevtana (cabazitaxel) has a lower dosage option that has just been approved. What has been the impact for your prostate cancer patients?

Dr. Stein: I use two doses of Jevtana (cabazitaxel): 25 mg/m. and 20 mg/ m.. The overall survival with both doses is identical, but at 25 mg/m., the PSA is more affected as opposed to the 20 mg/m.. In other words, you have more PSA decline on the 25 mg/m. than you have on the 20 mg/ m.. Of course, you have less toxicity on the 20 mg/m.. For those men who really follow their PSAs very closely, I might, all other things considered, recommend the 25 mg/m.. For most men, I think the 20 mg/m. is just fine. For Taxotere (docetaxel), the full dose is 75 mg/m.. There’s little evidence that you lose much in the way of efficacy if you go to 50 mg/m. to avoid toxicity, and I’ll do that frequently.

Is there anything men can do to prepare themselves for these side effects?

Dr. Stein: Aside from communicating with their doctors and taking Claritin if you’re receiving Neulasta (pegfilgrastim), I’m not sure there is anything you can do.

Is there anything else you’d like patients to know about chemotherapy for prostate cancer?

Dr. Stein: These are very realistic options for patients. Men can tolerate Taxotere (docetaxel) for maybe six to eight cycles. It’s hard for men to get more. With Jevtana (cabazitaxel) it’s unbelievable how much people can get because the toxicity is less. I know of a man who received 55 continuous cycles of Jevtana (cabazitaxel) and did extremely well. My own personal record is 33 cycles. In one of those cases, the patient had a 99% response in his PSA; he lived three extra years. He did extremely well. I had another man who also got 33 cycles. His PSA was roughly 50 to 70 and it stayed that way for 33 cycles before he started to progress. I have seen quite a few remarkable responses.

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Clinical Trial: Intravenous Vitamin C + Taxotere (Docetaxel)

Dr. Channing Paller, an Assistant Professor of Oncology at Johns Hopkins University School of Medicine, focuses on translational research and clinical trials of developmental therapeutics in prostate and other solid tumors.

She is keenly interested in the rigorous evaluation of natural products in cancer treatment.

Prostatepedia spoke to her about her Prostate Cancer Foundation instigated and Marcus Foundation funded clinical trial on combining intravenous Vitamin C with Taxotere (docetaxel).

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Dr. Channing Paller: One of my interests is studying natural products that people take as dietary supplements. We don’t know whether they work or whether they cause harm, so I test them. Several of my clinical trials study these compounds rigorously in a placebo-controlled fashion, as we would with any cancer treatment.

I knew about a recent randomized study of high dose intravenous ascorbic acid (vitamin C) in ovarian cancer patients, which showed that ascorbic acid treatment combined with standard chemotherapy reduced toxicities from the chemotherapy and also trended towards improved overall survival. Vitamin C enabled the patients to receive more cycles of chemotherapy, and that was associated with longer overall survival.

In response to the findings in ovarian cancer, the Prostate Cancer Foundation sent out a request for proposals for early stage research on vitamin C’s role in treating prostate cancer. We decided to initiate a large (60 patient) placebo-controlled trial with co-primary endpoints of quality of life and cancer response to the combination of intravenous (IV) vitamin C and chemotherapy. We are extremely grateful to the Marcus Foundation for supporting the trial.

We chose Taxotere (docetaxel) because it was first line and an easy place to start to answer the question. Jevtana (cabazitaxel) would have worked just as well.

What can patients expect to happen during the trial?

Dr. Paller: We are conducting a randomized placebo-controlled Phase II trial of standard-of-care Taxotere (docetaxel) for metastatic castrate resistant prostate cancer with either ascorbic acid or placebo, which is electrolytes and hydration, given twice a week in between the cycles of chemotherapy every three weeks. Some people say that this is too big a commitment, so they get to take breaks if needed. They can miss a session or two here or there. They can even take two weeks’ break, if needed. We’re trying to help people live better, not chain them to the clinic.

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