Medical Minute 4-18: Doubling Prostate Cancer Survival

By: Vanessa Welch Email
By: Vanessa Welch Email

As a prostate cancer survivor, Ray Caruana is no stranger to doctors. Ray has lived with cancer for 17 years.

"I was devastated being diagnosed with cancer, but it doesn't have to be a death sentence," said Ray Caruana.

He's had a prostatectomy, radiation and hormone therapy. Doctor Roberto Pili says eventually patients stop responding to treatments.

"Inevitably, these cancer cells learn how to survive either without testosterone or with very low levels of testosterone," said Roberto Pili, M.D., Professor of Oncology at Roswell Park Cancer Institute in
Buffalo, NY.

He's now studying a biologic agent, Tasquinimod, to help men who are running out of options.

"I would define this new agent as quite promising."

It's one pill, once a day, and it appears to pack a one-two punch. It disrupts the formation of new blood vessels to the tumor and also improves the body's immune response to the cancer.

"The idea is to treat prostate cancer as a chronic disease."

Ray's been on the drug for a year. His cancer is stable

"Hopefully, it's going to continue to work."

He's learned to appreciate life's little moments -- like a cup of coffee with his wife. Nearly two decades after his diagnosis, his philosophy is simple.

"I don't worry too much about the future. I just live for today."

For more information on other series produced by Ivanhoe Broadcast News contact John Cherry at (407) 691-1500, jcherry@ivanhoe.com.

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MEDICAL BREAKTHROUGHS - RESEARCH SUMMARY:

BACKGROUND: Prostate cancer is one of the most common types of cancer in men. It usually grows slows and may initially remain confined to the prostate gland. Some types of prostate cancer grow slowly and may need minimal or no treatment. Other types are aggressive and may spread quickly. When prostate cancer is detected early, patients have a better chance of successful treatment.

SYMPTOMS: Patients with prostate cancer may not have symptoms in the early stages of the disease. More advanced prostate cancer may cause symptoms such as trouble urinating, decreased force in the stream of urine, blood in the urine, blood in semen, swelling in the legs, discomfort in the pelvic area or bone pain.

WHO'S AT RISK? The risk of prostate cancer increases with age. This type of cancer is most common in men over age 65. Black men also have a greater risk of prostate cancer compared to men of other races. A family history of prostate cancer may also increase a man's risk. Obesity is another risk factor. Obese men who are diagnosed with prostate cancer are more likely to have advanced disease that's more difficult to treat.

TREATMENTS: Men who are diagnosed with a very early stage prostate cancer may not require treatment right away. Some men never need treatment. Doctors may recommend "watchful waiting," where they perform regular follow-up blood tests, rectal exams and biopsies to monitor the progression of the cancer. In other cases where a man's cancer is progressing, surgery, radiation, hormone therapy, cryoablation, high-intensity focused ultrasound treatments or chemotherapy may be used.

NEW THERAPY: In a clinical trial, a new biologic agent, known as tasquinimod, is being used to treat men with advanced prostate cancer that has progressed on hormone therapy. This oral drug disrupts the formation of new blood vessels to the tumor and improves the body's immune response to the cancer. After six months on tasquinimod, 69 percent of men in the study showed no disease progression compared to 37 percent of men on placebo. The most common side effects experienced by the participants were gastrointestinal problems, fatigue and bone pain. There were rare occurrences of heart attack, stroke and deep vein thrombosis in the study subjects. Researchers are now starting a phase III trial to further test the drug.

FOR MORE INFORMATION, PLEASE CONTACT:
Annie Deck-Miller, Senior Media Relations Manager
Roswell Park Cancer Institute
Buffalo, NY
Annie.Deck-Miller@RoswellPark.org

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THE FOLLOWING IS AN IN-DEPTH INTERVIEW WITH THE DOCTOR FROM THE STORY ABOVE:

Roberto Pili, MD, professor of oncology at Roswell Park Cancer Institute in Buffalo, NY, talks about a new drug to treat advanced prostate cancer.

Tell me, how big a problem is prostate cancer in the U.S.?

Dr. Roberto Pili: Prostate cancer is the number one cancer in the male population. More than 230,000 patients each year in the United States are diagnosed with prostate cancer.

The prognosis is really dependent on when the cancer is diagnosed, right?

Dr. Roberto Pili: Absolutely. If we are able to diagnose prostate cancer early on, we can cure more patients.

Do patients usually present with symptoms? Is it usually caught early?

Dr. Roberto Pili: As you probably know, there is a lot of controversy on how we can screen for prostate cancer. There are people who advocate for screening every patient for prostate cancer with a PSA screening (Prostate Specific Antigen). More lately the recommendation is not do a mass screening for prostate cancer, but to do early detection in high-risk patients. Patients who are African American have a high risk to develop prostate cancer, and so do patients who have family history of prostate cancer. Those patients should have PSA screening done at an early age.

When the cancer is more advanced, what are the options for the patient?

Dr. Roberto Pili: The agent that we studied in the clinical trials was tested in patients with metastatic disease, meaning when the prostate cancer recurs after the initial treatment, like surgery or radiation. When we talk about metastatic prostate cancer, that is when the disease, unfortunately, has not been cured with either radiation or surgery – and an early sign of disease recurrence is rising PSA. We can test the blood and, after surgery, the PSA should be undetectable, but if it starts rising that is a sign that there are still some cancer cells producing these proteins somewhere in the body. The number one site where the prostate cancer goes is to the bones, but it can go to lymph nodes and can pretty much go everywhere. So, when we detect the presence of cancer cells in the bones, for example, with a bone scan at that point we define the disease as a metastatic disease. The treatment options are primarily based on ablation of the testosterone. Prostate cancer cells need testosterone in order to stay alive and to proliferate, and we have drugs that can ablate the production of testosterone.

Like hormone therapy?

Dr. Roberto Pili: That is a form of hormone therapy, yes.

When we talked to Ray, he said he developed a resistance to it. Is that a common occurrence? Do a lot of people develop that after they have been on it for a while?

Dr. Roberto Pili: Yes, unfortunately, hormone therapy does not cure prostate cancer when it comes back. So, inevitably the cancer cells learn how to survive either without testosterone, or with a very low level of testosterone. At that point we define the disease as castrate-refractory disease, where the normal shot no longer works and we need to think about some additional therapy.

When it is metastatic and you know it’s in the bones or the blood or wherever it is, you are looking to prolong the patient’s life because people can live with this disease, right?

Dr. Roberto Pili: Absolutely.

So, when someone becomes resistant to hormone therapy, you need other drugs or agents or something else to help.

Dr. Roberto Pili: Absolutely. The idea is to treat the prostate cancer as a chronic disease even when it’s back and to try to add years of life to our patient while looking at the quality of life. That is, adding not just years to life but adding life to years.

Tell me about this new agent. It’s a biologic agent, right?

Dr. Roberto Pili: It is a biological agent. Tasquinimod is not the classical chemotherapy; it is not the classical hormone therapy. It’s a small molecule, and it has been shown in pre-clinical testing that it may affect blood vessel formation on the one hand and can affect the immune system too, so it might control prostate cancer by cutting off the blood supply to the prostate cancer and by stimulating the new system to reject prostate cancer. It’s a two-fold mechanism.

And so, when you say it might do this, you’re not sure it really does this. It’s just the theory.

Dr. Roberto Pili: That’s the hypothesis that has been proposed in the laboratory studies, yes.

When patients have been given this drug, clearly something is happening. How is this agent administered? Is it a pill?

Dr. Roberto Pili: It’s a pill the patient takes every day, continuously.

It’s taken just one time a day, and are there side effects involved?

Dr. Roberto Pili: Any agent has a side effect. The major side effect that has been encountered during the clinical testing has been fatigue, loss of appetite, some constipation, some increase of electrolytes, or amylase, some enzymes that are present in the pancreas and the liver. In general this has been mild toxicity, mild events that in general tend to resolve with chronic administration of this agent.

So, it does improve if they are on it for a while?

Dr. Roberto Pili: In some patients we do see that the initial side effects may improve and they are just transitory. In some patients we do see that these side effects are maintained, so in the clinical trials we reduced the dose. The patient has been able to stay in the study, but at the lower dose.

So what results have you seen thus far?

Dr. Roberto Pili: The interesting aspect of this agent is that it doesn’t belong to the current class of drugs that we have for prostate cancer. It is neither a chemotherapy agent nor a hormonal therapy agent. As we said, it may have this dual mechanism by blocking the blood supply and stimulating the immune system. What we saw in patients with metastatic disease that went through chemical castration, where patients were randomized to the active agent rather than taking the placebo, in patients that were taking the agent we saw a clinical benefit in terms of disease progression-free survival. That means that at six months 69% of the patients who were randomized to the active agent were still without progression as compared to 34%, only, in the placebo arm. When we look at the median time of clinical benefit, there was a doubling of the clinical benefit between the placebos as compared to the active agent, Tasquinimod.

And, when you say it hasn’t progressed you mean the PSA levels are stable. They haven’t risen.

Dr. Roberto Pili: Well, that’s interesting because this is one of the first studies where we didn’t really assess disease progression by PSA. PSA was not a criterion to determine whether or not the patient’s disease was progressing. The criteria to determine whether or not the patient was progressing were primarily based on the scan, whether it was a bone scan or CAT scan.

So, what are you looking for, just the number of cells?

Dr. Roberto Pili: Well, we look for the number of lesions on the bone scan; if there are additional lesions on the bone scan, that means that the disease is progressing, or if on the CAT scan there are some lesions that are growing, we can determine the rate of the growth of the lesion. Based on those parameters we can tell if the agent is still having clinical benefit or not.

So, all patients in this study had cancer that had spread to the bones?

Dr. Roberto Pili: All the patients had disease that had spread. The majority of the patients had disease in the bones, but there were patients that had disease in the bones and the lymph nodes. There was a small fraction of patients who had disease to the visceral organs like the liver, and in general those patients don’t do as well as other patients. But the interesting thing we did observe was that this agent was as effective in the bone as in the liver. There was no significant difference in total clinical benefit as to where the cancer was.

Well, that’s a big deal.

Dr. Roberto Pili: That was something very encouraging, because there are some agents that may be more effective when the cancer is in the bones rather than when the cancer is, for example, in the liver.

So, the patient we interviewed earlier, where is his cancer?

Dr. Roberto Pili: The patient you interviewed today was one of the few patients who did not have disease in the bones, but have the disease in the soft tissue outside the bone. This patient in particular had stabilization of the disease and also some drop in the PSA. Overall we did not see an effect on the PSA progression, but we saw an effect on the disease progression. And that’s where you take into account that probably looking at PSA sometimes may be misleading. There are some agents, like this Tasquinimod, that may still work very well despite the fact that it doesn’t control the PSA.

Where on the study are you? Are you still recruiting? Are there other sites across the country?

Dr. Roberto Pili: The study has been completed. There was an international study run here in the United States and in Europe, but this study has been completed and we have already presented the results at our annual meeting at ASCO (the annual meeting of the American Society of Clinical Oncology) in June 2010.

Is there another phase to this study?

Dr. Roberto Pili: Yes. This was a larger phase to randomize out double blind placebo control, so the next step will to be to confirm these exciting results in a larger study. Call it a phase 3 randomized study with the same design, but with a larger patient population.

Has that started recruiting yet?

Dr. Roberto Pili: It hasn’t started yet. The protocol is under development and we are hoping to open this study this year.

So, if someone is watching this and they want to know more about it or get involved, there is another study starting. Will the same sites be available?

Dr. Roberto Pili: Actually, there will be more sites involved.

So for people around the country, chances are there will be a place near them?

Dr. Roberto Pili: Absolutely.

And where should they find more information about this?

Dr. Roberto Pili: When the study is activated, it will be registered in the National Cancer Institute website at clinicaltrials.gov. Once the study is open to a pool, the patients can find it and get information about the closest site available to them.

How do we refer to this drug, TASQ?

Dr. Roberto Pili: Yes, TASQ.

Is that a generic name?

Dr. Roberto Pili: Yes.

If this is the final phase of the study, what’s the time line for this drug to be available on the market? Would you say 5 years if it continues to show efficacy?

Dr. Roberto Pili: I believe the phase 3 study will be implemented next year and the study will likely last for a couple of years so, probably, if it’s going to be confirmed as a potential new agent for prostate cancer, we might be able to see the approval of this compound within the next five years.

So, any last thoughts? How promising do you think this is?

Dr. Roberto Pili: Looking at the results of this study and looking at also the toxicity profile of this compound, I would define this new agent as quite promising. The treatment for prostate cancer when it has recurred is really evolving dramatically over the past few years. We used to have just normal therapy. We had only one chemotherapy approved, and now we have a second agent in chemotherapy. We have a vaccine type of an approach that has been approved recently. We have a new agent that can still affect the hormone production. And so the treatment options for a patient with advanced prostate cancer are really improving, and this agent may find a very special place, in particular, in patients who have disease that is resistant to hormone therapy, advanced metastatic, but with minimal symptoms. So, for patients who do not have a lot of symptoms with prostate cancer and are probably not willing or ready to undergo chemotherapy, this agent may indeed delay the time when the patient needs, eventually, be treated with cytotoxic agents.

And that will probably mean a lot for patients. What could it do for patients?

Dr. Roberto Pili: Again, we believe this new agent can potentially delay the time of progression of the disease. Hopefully, it will help the patient live longer and have a better quality of life. We need to always be attentive that any intervention we do on our patient is not a major burden for them. But there is new hope for the treatment of prostate cancer.


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