Prostatepedia

Conversations With Prostate Cancer Experts


Leave a comment

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?

Not a member? Join us.

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.


Leave a comment

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.

Not a member? Join us.

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.


Leave a comment

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.

Join us to read more conversations about chemotherapy for prostate cancer.


Leave a comment

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?

Not a member? Join us.

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.

Join us to read the rest of this month’s conversations about chemotherapy for prostate cancer.


Leave a comment

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).

Paller-20537-111ret

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.

Join us to read more about Dr. Paller’s trial.


Leave a comment

Dr. Ken Pienta: Chemo For Prostate Cancer

Dr. Kenneth J. Pienta, of the Johns Hopkins University School of Medicine, is an international expert in the development of novel chemotherapeutic agents for prostate cancer. He was the recipient of the first annual American Association for Cancer Research Team Science Award and is the author of more than 300 peer-reviewed articles. He frames this month’s conversations about chemotherapy for us.

Pienta_lab_Background

Not a member? Join us.

In 2018, chemotherapy for prostate cancer continues to be one of the many options we have to lengthen the lives of patients suffering from metastatic prostate cancer. There are still multiple other therapies that we don’t consider chemotherapy. Second-generation anti-androgen therapies like Zytiga (abiraterone), Erleada (apalutamide), and Xtandi (enzalutamide) are all now standards of care in castrate-resistant prostate cancer. We also have Xofigo (radium-223) as an option for patients with bony metastases.

There are two chemotherapies that have been approved for prostate cancer: Taxotere (docetaxel) and Jevtana (cabazitaxel). Now, the real challenge for patients and providers is when to use those chemotherapies.

Multiple studies have demonstrated that, when you’re newly diagnosed with metastatic prostate cancer, it may be beneficial to receive a limited number of doses of Taxotere (docetaxel) at the start of hormone therapy. That’s especially true if you have multiple places where the cancer has spread. That’s not correct for all people, but for some patients, it is a good option. More and more physicians are prescribing Taxotere (docetaxel) with a luteinizing hormone-releasing hormone (LHRH) antagonist at the start of therapy.

However, that doesn’t mean you cannot use Taxotere (docetaxel) after other things have failed. If you failed second-line hormone therapy or have failed radium therapy, Taxotere (docetaxel) is still a good option that helps people live longer.

Jevtana (cabazitaxel) continues to be a good chemotherapy option if patients have failed Taxotere (docetaxel).

Thank goodness we’ve seen over the last several years an increase in the number of drugs available to treat metastatic prostate cancer in addition to chemotherapy. Chemotherapy has been around for quite a while now, but there is still a role for it.

Again, the challenge for all of us is: when do we slot them in for you? The chemotherapy we use for prostate cancer is really a single agent chemotherapy, either Taxotere (docetaxel) or Jevtana (cabazitaxel). This is not the multi-agent therapy we use for other cancers, so the idea of major side effects is a bit overblown. For example, nobody vomits from chemotherapy for prostate cancer. The drugs we use to prevent that are too good.

We also have gotten much smarter about limiting the number of doses we use. We don’t necessarily give chemotherapy until it doesn’t work anymore. Often, we just give several doses and then take a break. If you get more than a couple doses of chemotherapy, you will still lose your hair temporarily.

Chemotherapy can make you feel more tired when it lowers your blood count, and it can make you more susceptible to infections, but people are very rarely hospitalized now for an infection from chemotherapy. It’s virtually unheard of that somebody would die as a side effect of chemotherapy.

The major side effect of Jevtana (cabazitaxel) tends to be diarrhea, but again, as we’ve learned about the dosing of that drug, that has become more manageable.

Another side effect of both drugs can be peripheral neuropathy, which is tingling in the fingers and toes. But we watch for that too. If you start to develop that, we tend to stop the drug. These are very tolerable medicines.

The word chemotherapy always evokes images of horror, but chemotherapy in 2018 is a lot different than it was even five years ago. We just know how to give chemotherapy much better. When I started in the field 30 years ago, if you had metastatic castrate resistant prostate cancer, survival was 6 months. Now, with the advent of all these newer therapies, we’ve gotten much better. The landscape of how to treat prostate cancer has changed completely in the last five years. It will change completely again in the next five years. The challenge is in what order are we going to use all these powerfully good drugs rather than having only one drug to give or none at all.

For us as physicians, it’s an exciting time to take care of men with prostate cancer.

Join us to read this month’s conversations about chemotherapy for prostate cancer.


Leave a comment

The Genomic Revolution Comes To Prostate Cancer

Dr. Oliver Sartor, the Laborde Professor of Cancer Research in the Medicine and Urology Departments of the Tulane School of Medicine, is one of the leading researchers in advanced prostate cancer today. He is also the editor-in-chief of Clinical Genitourinary Cancer and the author of more than 300 scientific papers.

Dr. Sartor puts this month’s conversations about prostate cancer genomics into context for us.

“We can divide genomics into two different categories. The first category is germline genomics, which is the DNA with which you’re born. It’s clear that about 12% of people with advanced prostate cancer will have alterations in their inherited DNA, in particular in genes involved with DNA repair. Most common of these alterations are BRCA2. There are a variety of others that are somewhat prevalent, including ATM, CHEK2, and BRCA1. There are others that are more rare.

The implications of these germline mutations are significant for the patient: in certain configurations they may predispose a cancer to be sensitive to certain therapies, such as PARP inhibitors or platinum-based chemotherapy or (rarely) immunotherapy. There is more complexity, but knowing the germline mutation helps the informed clinician make decisions. In my practice, we test all patients with advanced prostate cancer for these germline mutations. (A National Comprehensive Cancer Network guideline suggests the same approach.)

These germline mutations represent the DNA with which you’re born. That DNA is going to have repercussions if also mutated in your family members. Men who have some of these DNA repair mutations have an increased risk of prostate cancer. In addition, there is a small increased risk of pancreatic cancer and male breast cancer for those with some of the germline mutations. Around 30% of men with BRCA2 will be diagnosed with prostate cancer in their lifetime, but that cancer is more likely to be aggressive if diagnosed. With regards to females, it’s particularly important. Females with DNA repair defects are more likely to have breast and ovarian cancer. Female with DNA repair mutations, in particular BRCA1/

BRCA2, ought to consider having their breasts or ovaries removed at an appropriate time. Prophylactic surgery has been demonstrated to be potentially life-saving for those individuals. The risk of breast cancer may be as high as 70% and the risk of ovarian cancer may be as high as 40%.

Thus, for these germline mutations there are implications for treatment and implications for the patient’s family.

We should be doing prostate cancer screening earlier in men with these DNA repair defects for prostate cancer; we should be doing biopsies at a PSA of 3 or higher, and perhaps even lower, for younger men known to be at risk. Starting screening at age 45 has been suggested by some. In addition to germline genomics, we need to also talk about somatic genomics. Data indicates that about 60% of individuals who have a DNA repair germline mutation are likely to have another second genetic mutation occur within their tumor. In addition, many of the tumors can acquire an alteration in their tumor DNA even when the germline is normal.

Taken together, about 20 to 25% of men may have DNA repair mutations in their tumor’s DNA. That makes them particularly sensitive to certain therapies such as the PARP inhibitors, as I mentioned earlier, or platinum chemotherapy. When you have two DNA repair mutations in the same cell, the likelihood of response to these agents appears fairly high.

There are also other DNA defects of considerable interest, such as alterations of the mismatch repair genes MSH-2 and MSH-6. When these alterations do occur, there is a potentially increased probability of responding to immunotherapy such as the new PD-1 inhibitors.

Overall, the guiding light today in genetics in my practice is to look at both the germline DNA and the tumor DNA. I choose to look at the tumor DNA circulating free DNA (cfDNA) tests, in particular the Guardant Health assay. The ability of other assays to corroborate the Guardant Health findings is not yet clear. There is clear data to indicate that different assays give different results, but nevertheless, I think in the early exploratory phase we’re in now, it’s important to begin to test patients in order to better understand their genomics and hopefully guide us towards better therapies. This will happen part of the time but certainly not all of the time.

There is more to the story of prostate cancer genetics. We’ve looked at androgen receptor mutations that can have implications for a response to Androgen Receptor directed therapy, such as Xtandi (enzalutamide), Zytiga (abiraterone), and Erleada (apalutamide). We’re dissecting a number of permutations that occur. It’s a complex scenario, because very few men have only one mutation. Most have multiple mutations. And in most cases, these mutations are not targetable with current therapies. This is very important for people to know.

Everybody thinks if they get a genomics test that means they’ve got a treatment. It’s not the case. Many times we get the genomics results and find that there are no known treatments we can use for that man’s particular alteration. That said, there is a subset of men who will have informative genomics while many more people will have non-informative genomics.

There is a final issue I’d like to discuss. There is currently a bit of a debate amongst physicians over the utility of PARP inhibitors such as Lynparza (olaparib) as compared to platinum chemotherapy. But it is noteworthy that platinum-based chemotherapies are inexpensive compared to PARP inhibitors. This does not require a clinical trial. (Most men will access PARP inhibitors through a clinical trial, although sometimes insurance companies are willing to try.)

As it turns out, neither the platinum-based chemotherapies nor the PARP inhibitors will be effective forever, so we do need strategies to manage patients after PARP inhibitors or platinum-based chemotherapies fail. Currently, that space is unexplored. We have to gather much more data before we can make conclusions about those with underlying DNA repair defects who have failed platinum-based chemotherapy or PARP inhibitors.

This is an area of active and important investigation that represents a conundrum for many patients today. I’ve got a patient right now going through this. We’re debating what to do next. I’ve tried to be as honest as I can when I say, “I don’t know what to do, but we’ve got to try something.”

We are in the middle of a revolution, but the parts and pieces are not yet clear. For some, understanding tumor genetics at the current level is helpful. For others, it is perplexing and expensive.

Join us to read this month’s conversations about prostate cancer genomics.

(Already a member? You can read all conversations in your copy of April’s Prostatepedia.)