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Conversations With Prostate Cancer Experts


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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.

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


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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.

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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.


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Dr. Daniel Spratt: On Becoming A Doctor

Dr. Daniel Spratt is a radiation oncologist and the Chair of the Genitourinary Division of Clinical Research at the University of Michigan Health System.

Dr. Spratt talks to Prostatepedia about why he became a doctor.

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Why did you become a doctor?

Dr. Daniel Spratt: There are no physicians or healthcare workers in my family. I took an unconventional path to becoming a doctor. I started working as a personal trainer when I turned 18. I was always involved in fitness and exercise. I took some time off from going to college and worked one-on-one with clients.

At that time, I noticed that I liked being able to help change people’s lives and have that unique interaction. But there are limitations to what a personal trainer can do for a person. That inspired me to go back to college, focus on the research, and go to medical school to become a radiation oncologist.

How did you make your way to radiation oncology versus urology?

Dr. Spratt: In medical school, we rotate through a bunch of different specialties. All along, I thought I was going to be a neurosurgeon; that was my focus and my research. But I started to realize that I love to connect, to have the time and flexibility to discuss how patients are doing. I care more than just about the technical treatment. I enjoy emotionally connecting with patients.

The radiation oncology industry is a unique specialty in that a machine delivers our treatments, and then we get to see the patient. I almost do two things at once. If a surgeon is operating all day, they can’t see anyone other than the one patient in front of them. I get to see and treat dozens of patients a day.

Are you still involved in the exercise world?

Dr. Spratt: Definitely. It is not as strong, but if you spoke to any of my patients, they’d tell you that I prescribe exercise to all of them. The side effect profile for my patients who are inactive versus the ones who are active is like night and day. It’s amazing how patients undergoing prostate cancer treatment, including radiation and especially hormone therapy, are improved by exercise. It doesn’t need to be joining a gym—just being active in some way.

The guys who are active have much fewer side effects during treatment. I jokingly prescribe exercise while

I prescribe radiation to them.

Maybe you shouldn’t joke and really do it!

Dr. Spratt: Exactly. I don’t think a pharmacy can fill that.

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Shop Around For A Radiation Therapist

Dr. William Hall of the Medical College of Wisconsin offers advise to patients looking for a radiation therapist.

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Dr. Hall says: Radiation therapy is an extremely technical specialty that is rapidly evolving. Many patients think that radiation therapy is the same, regardless of where they receive it.

That is not so.

Expertise, delivery methods, and the unique methods of radiation therapy administration can vary tremendously from hospital to hospital. That’s extremely valuable for patients to understand.

You should seek a radiation oncologist who specializes in your type of cancer, someone who focuses their research and clinical efforts on a few types of cancer. In larger academic centers, radiation oncologists tend to do that.

Join us to read the rest of Dr. Hall’s comments on radiation therapy for prostate cancer.


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Radiation Therapy + The Abscopal Effect

Dr. Charles G. Drake of New York Presbyterian/Columbia University Medical Center, discusses the rare but intriguing abscopal effect.

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Dr. Charles Drake says: There was an article in the New England Journal of Medicine showing an abscopal response with Yervoy (ipilimumab) anti-CTLA-4 in a patient with melanoma. It was a beautifully done paper with nice immunological correlates. After that got published, we found that radiation oncologists and medical oncologists were giving people a combination of immunotherapy and radiation and were telling patients they would get abscopal responses. But that’s a bit overly ambitious. In the clinic, it’s not that easy. It’s going to be a while before we understand what’s needed therapeutically to be able to induce abscopal responses in the majority of patients. It’s going to take a little more work before we can have that happen broadly. On the other hand, if we can make it work, it’ll be fantastic. Dr. Hammers’ trial combining anti- PD-1, anti-CTLA-4, and radiation in kidney cancer is perhaps a more clever approach. That may be what we need to do.

In other words, abscopal responses do happen, but we don’t exactly know why or how and can’t reproduce it?

Dr. Drake: Exactly. And it doesn’t happen nearly as often as we’d like.

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Why Combine RT + Immunotherapy?

Dr. Charles G. Drake, of New York-Presbyterian/Columbia University Medical Center, discusses the thinking behind combining radiation therapy with immunotherapy.

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Dr. Drake says: “The basic idea is that radiation, and perhaps other local modalities like cryotherapy, leads to destruction of tumor cells. If they’re destroyed in a way that’s immunogenic or pro-immunogenic, then the dying cells are taken up by resident antigen-presenting cells. These antigen-presenting cells get activated; they traffic to the draining lymph node, if you’re lucky. If they traffic to the draining lymph nodes, and then activate a systemic immune response (T cells), then maybe you can turn a local therapy into a systemic therapy. When that happens, it’s called the abscopal effect. We can demonstrate this in mice fairly readily, but it’s quite hard to demonstrate in humans.

In the literature, it’s not that common. There’s a review paper that reports around 60 total cases in the world that are clearly documented. But if you talk to people who take care of patients, everybody has one or two that they can talk about.”

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Dr. Charles Drake On A Memorable Patient

DRAKE charlesDr. Charles G. Drake is the Director of Genitourinary Oncology, Co-Director of the Cancer Immunotherapy Program, and Associate Director for Clinical Research at the Herbert Irving Comprehensive Cancer Center, New York-Presbyterian/Columbia University Medical Center.

Dr. Drake discusses a patient whose case intrigued him.

Have you had a particular patient who changed how you approach your work?

Dr. Charles Drake: Absolutely. I had a gentleman who had metastatic, castrate-resistant prostate cancer. He had been treated with hormonal therapy. He was about to go on chemotherapy. He had progression in his bone lesions, but he developed hematuria.

On CT scan, there was a fairly clear lesion in his bladder. We couldn’t tell what it was just by the scans, and his PSA was doubling quickly, it had reached 30 or so in less than a couple of months. We sent him to Dr. Ronald Rodriguez, who was at Johns Hopkins at the time, and he thought it looked like this was probably metastatic prostate cancer invading the gentleman’s bladder. Dr. Rodriguez did a transurethral fulguration, meaning he burned all of the tumor he could find in the bladder. After the procedure, he told me that there was a fair amount of prostate cancer left behind. While the procedure went well, and he got most of the tumor, he didn’t get all of it.

What happened next was fascinating. The patient’s PSA dropped. His PSA went from 30 to 20 to 10. It eventually nadired, or reached its lowest point, at less than 1 ng/ ml and he remained in remission for nearly two years. Although clearly anecdotal, in my mind, there is almost no question that this was one of those anecdotal abscopal responses, which makes you believe that it can happen. Almost certainly that was what happened for this patient. I’ll never forget it, frankly.

Interesting. An unexpected systemic response from local treatment, right?

Dr. Drake: Yes. It was brilliant. Just by treating the local disease in the bladder, this gentleman did well for over two years before it apparently progressed again, and he wound up getting chemotherapy. He also did very well with the chemo, so in my hopeful view, that suggests that maybe this fulguration procedure sparked a systemic immune response.

Join us to read the rest of Dr. Drake’s comments on the elusive abscopal effect.