A New Immune Treatment Combination

BY MARK SCHOLZ, MD

In my last blog I contended that of all the different ways to treat cancer—hormone therapy, chemotherapy, radiation or surgery for example—immune therapy has the greatest potential to save lives: Only the immune system, by its very nature, has the ability to adapt to the many thousands of varieties of cancer.  Also, new breakthroughs in understanding how it works have led to real progress inharnessing the immune system to fight cancer. 

One discovery—that the immune system uses a specific type of immune cell called the “dendritic cell” to detect cancercells—led researchers at a company called Dendreon to develop a five-step process for enhancing dendritic cell function.

First the dendritic cells are filtered out of the blood for processing in the lab. Second, the dendritic cells are exposed to prostatic acid phosphatase (PAP), a protein that can be identified on the surface of almost all prostate cancer cells. Third, the dendritic cells are incubated with granulocyte macrophage cell stimulating factor (GM-CSF) which converts the dendritic cells from their dormant state into an activated form. Fourth, the activated dendritic cells are infused back into the patient’s blood. Fifth, once back in the body, the activated dendritic cells recruit the killer cells of the immune system, the T-cells, to attack the cancer cells, which are identified by having PAP on their surface.

This five-step process, called “Provenge,” is an elegant and clever way to enhance immune function. Two prospective, double-blind, placebo-controlled trials have proved the efficacy of Provenge.  However, one cannot help but wonder why—since Provenge is simply an enhancement of the immune system’s normal function—is all this artificial stimulation in the lab necessary?  Why aren’t the dendritic cells in the cancer patient’s immune system detecting the cancer cells spontaneously and recruiting T-cells to attack it?

Another breakthrough has been the discovery that a normally functioning immune system, like all the systems in our body, is tightly organized by a variety of controlling hormones. Obviously, both underactivity and over activity of any system, be it the heart, the pancreas or the immune system, can be dangerous.  Now, new research reveals that malignant cells actually manufacture and release excess amounts of controlling hormones that trick the immune system into remaining dormant.  Thus the natural process of immune system detection is directly inhibited by the cancer.

Provenge partially circumvents this problem by activating the dendritic cells outside the body in the lab. But the dendritic cells still face a hostile inhibitory environment after they are re-infused. The question arises, “Wouldn’t Provenge work even better if the immune environment in the cancer patient could be rendered more “friendly"?”

In this era of rapid technological advancement it is not surprising that amedicine designed for this specific purpose is already on the market! Yervoy, a monoclonal antibody from Bristol-Myers Squib, was FDA approved to treat malignant melanoma in 2011.   Yervoy enhances immune function by counteracting the excess amounts of suppressive hormones being released by the cancer. I heard one researcher characterize Yervoy as the most powerful method available for “taking the brakes off” the immune system.

Provenge and Yervoy used together are so attractive conceptually that the only question remaining is about the optimal method of delivery.  Yervoy, unlike Provenge, can have serious side effects.  In excess amounts it can induce the immune system to run wild and start attacking the organs in the body like the liver, thyroid and intestines. Caution dictates beginning with a small initial dosage of Yervoy.

In the study we will be conducting at Prostate Oncology Specialists in Marina del Rey the first three patients we treat will be given one-twelfth of a normal dose of Yervoy one week after the Provenge is completed.  The second group of three patients will receive a one-sixth dose of Yervoy.  The third group of three patients will get three-twelfths of a Yervoy dose. All patients will receive full-dose Provenge and will be closely monitored for disease response, immune function and for possible side effects.

Provenge and Yervoy are just two of the many exciting new methods being studied for harnessing the immune system to fight cancer.  However, to my knowledge, we at Prostate Oncology Specialists are privileged to be the first to test the effectiveness of these two exciting treatments in combination.  Our first patient is scheduled to start on trial this month. 

PCRI: Prostate Oncology for the Masses

BY MARK SCHOLZ, MD

Dr. Steven Strum and I, medical oncologists who specialize in prostate cancer, founded the Prostate Cancer Research Institute (PCRI) in 1996. I still support the PCRI by donating my services as Executive Director. Through its conferences, helpline, newsletter and website, PCRI helps patients learn about optimal prostate cancer therapy.

Why is the PCRI important? “Modern” prostate cancer treatment, which is inherently biased toward surgery, is actually a throwback to the past. Prostate cancer is the last remaining type of cancer to have surgeons (urologists) directing care. Thirty years ago, because surgery was the only type of treatment available, cancers­ such as breast, colon, lung, pancreas and bone, for example, were supervised by surgeons. Now, every cancer (except for prostate cancer) is handled by medical oncologists—cancer specialists trained in a multimodality approach.  “Multimodality” means that all treatments (or treatment combinations) get equal consideration. Medical oncologists are trained to tailor therapy to the individual characteristics of each patient’s disease.

The problem is there are less than 100 prostate oncologists in the United States to serve more than three million prostate cancer survivors. That works out to a ridiculous ratio of 30,000 patients per prostate oncologist. To give you an idea of what a manageable patient-to-doctor ratio would be, at Prostate Oncology Specialists where I work with two other full time prostate oncologists, we have 1,600 active patients, a little more than 500 patients per oncologist.

Is prostate cancer an unusually simple cancer to manage?  No. It’s actually quite complex. What we term “prostate cancer” varies between extremes. There are low-grade forms that can be safely monitored; more serious types that require combinations of radiation and hormones; and “in-between” types that defy easy answers.  For men with the advanced, metastatic type of prostate cancer, the FDA has approved four new treatments in the last two years, more than I have seen in my last 20 years as a prostate oncologist.  Sequencing, timing, and combining these new treatments require skills few surgeons have time to master.

Sadly, simply providing up to date and accurate information to patients is not enough. Prostate cancer is not only complex, it is emotional. Patients and their families are all too often so frightened they need to be “talked down” from their emotionally charged state with professional support and encouragement. They can’t even begin to analyze their situation clearly until they calm down.

Also, when suddenly diagnosed with prostate cancer, many men have serious misconceptions that even professionals struggle to counteract. Three fallacies make men easy prey to a “just cut it out” mentality. First, men logically assume prostate cancer is just as dangerous as other cancers (see my October2012 blog, “The Un-Cancer”).  Second, men think the doctor who did their biopsy, their urologist, is a cancer expert. Third, they believe they need to make a quick decision before the cancer spreads. These mistaken beliefs mean men are at a severe disadvantage when seeking the truth.

PCRI tries to counter these problems by providing expert “one on one” support thorough its helpline and the online Blue Community. The PCRI has also recently initiated a new Mentor Program providing in-depth education for leaders of support groups.  We want everyone to understand their situation from the perspective of a prostate oncologist.  However, the magnitude of the task is daunting.  Every year almost a quarter of a million men— 650 men daily—get the shocking news that they have prostate cancer.

Even though this is my 17^th year serving the PCRI and the prostate cancer community, I am more energized, more focused and more determined than ever to make sure men with prostate cancer have the opportunity to get the best possible treatment.

However, the PCRI mission always needs financial support. PCRI heavily utilizes graphics, editing, internet and video to fulfill its mission. We also have expenses for bookkeeping, fundraising and grant writing. Every year PCRI undergoes a stringent “GAP” audit, documenting that more than 90% of dollars donated go to fund programs while less than 10% go to administrative or fundraising expenses.

If you are in a position to support the PCRI mission, your help would be greatly appreciated. Every donation increases our ability to get out much needed information to the prostate cancer community.

 

 

 

Happy New Year Announcement from Prostate Oncology Specialists

Jeffrey Turner, MD, Medical Oncologist, Joins Prostate Oncology Specialists in Marina del Rey, CA.

MARINA DEL REY, Ca., December 31, 2012 - Prostate Oncology Specialists is pleased to announce that Jeffrey Turner, MD has joined the prostate cancer specialist team. Dr. Turner is a board-certified internist and medical oncologist and will be specializing exclusively in prostate cancer with Mark Scholz and Richard Lam. Dr. Turner has been specializing in prostate cancer since 2009. He graduated cum laude from USC. Thereafter, he worked in research at UCLA studying infectious disease and molecular biology.  He earned his medical degree in Canada at Memorial University of Newfoundland and completed his internal medicine residency at the University of British Columbia and fellowship in medical oncology at the Medical University of South Carolina. Dr. Turner has published several articles on urologic cancers with an emphasis on prostate cancer.  He is a sub-investigator of a number of ongoing prostate cancer clinical trials.

Dr. Mark Scholz, Medical Director of Prostate Oncology Specialists commented, “Dr. Turner joins us during a time when the number of new prostate cancer treatments is exploding. He will add his expertise and knowledge to help patients make informed decisions. In 2012, we conducted clinical trials with Zytiga and Xtandi, agents that are now FDA approved.  We are presently evaluating new agents such as Curstersin, XL-184 and Ipilimumab in combination with Provenge.  We are happy to welcome a talented new member to the team who is familiar with all the many new treatment options for patients—this also includes Active Surveillance which is rapidly gaining acceptance as a viable treatment for prostate cancer.”

Active Surveillance remains very popular given the alternative risk of permanent side-effects from surgery, radiation, or cryotherapy. Dr. Turner added, “With the dramatic evolution of today's imaging techniques (including color Doppler ultrasound and MRI), Active Surveillance is best for men with Gleason 6, PSA<10, and clinical stage less than or equal to T2a.  Due to the fact that men with Gleason 6 prostate cancer have an incredibly low risk of mortality, Active Surveillance should remain a strong alternative.”
As skilled leaders in treating prostate cancer, our medical oncologists use PSA monitoring and color Doppler scanning to accurately monitor men on Active Surveillance. These techniques can detect early disease progression in men who may need to pursue treatment intervention.  

For more information about Active Surveillance or Prostate Oncology Specialists - visit: www.keepmyprostate.com or www.prostateoncology.com/activesurveillance

Revisiting TIP (Testosterone Inactivating Pharmaceuticals)

BY RALPH BLUM

Why Does TIP Work?
Testosterone is the hormone that causes boys to become men at puberty. Prior to puberty, the prostate gland is roughly the size of a small marble. Then, when the teenage surge of testosterone occurs, the gland expands to walnut size and begins producing semen. This transformation occurs because the cells of the prostate gland are uniquely sensitive to the presence, or absence, of testosterone. Lowering the level of testosterone in the blood causes the cancer cells to shrivel up a die because the cancer cells are derived from prostate gland cells and retain the same dependence on testosterone for survival.

Long Term Results
One downside to TIP is that while it shrinks the cancer, it does not, ultimately, kill every last cell. However, it has been my treatment of choice for the past ten years. Studies done at Prostate Oncology Specialists, Inc. show that after twelve months of TIP the amount of residual cancer is usually too small to be detected with a lesion-directed biopsy using color Doppler ultrasound. In most cases PSA drops to near undetectable levels (mine dropped to 0.125), and TIP has the added benefit of having anti-cancer effects throughout the body.

When TIP is stopped, testosterone levels gradually return to normal, and a number of men require no further treatment. Some men require periodic treatment with TIP to keep their PSA levels under 5.  And other men, rather than continuing with intermittent TIP, decide to go for surgery, seeds or IMRT. However, even this latter group has bought themselves on average of five plus years before risking the intimidating potential side effects of more radical treatments.

Side Effects of TIP
Although no prostate cancer treatment is free of undesirable side effects, most of the side effects of TIP (weight gain, muscle loss, loss of libido)   are preventable with proper management. And loss of libido, unlike impotence, is reversible when TIP is stopped. Meanwhile, although some of the magic may be gone while on TIP, most men find that they can still enjoy sex (and give pleasure to their partners) with a little help from Big Pharma. Viva Viagra!

Final Thoughts
I can think of only three reasons why this non-invasive alternative to surgery and radiation is not more often the treatment of choice for men with Intermediate-Risk prostate cancer:

1)  Patients never hear that it is an option: Urologists usually don’t suggest TIP to men with Intermediate-Risk cancer as a viable alternative to their preferred treatments—surgery and radiation.

2)  Doctors are unfamiliar with the TIP option.  Finding an oncologist with experience in state-of-the-art methods of administering TIP is still a challenge.

3)  Most men are shocked and fearful when they are first diagnosed with prostate cancer, and it’s hard to resist the emotional appeal of “Just cutting it out”—especially when the risks of more radical treatment are sometimes glossed over.

Thankfully, in 2002, when I learned that my PSA had bumped up to 18.3, my fear of being sliced open, or fried by radiation led me to Mark Scholz, and TIP. And although I would not describe my experience as “a day at the beach,” I am deeply grateful that I chose TIP, and, more importantly, ten years later, I am still here!