Combidex the Detective: Where has the Cancer Spread?

MARK SCHOLZ, MD

In our book, Invasion of the Prostate Snatchers, Ralph Blum and I devoted a chapter to the heartbreaking story of how Combidex, a revolutionary way to detect cancerous lymph nodes, was shot down by the FDA.  Detecting cancer in the lymph nodes is the Holy Grail of cancer scanning because the lymph nodes are the first place prostate cancer usually spreads if it leaves the prostate.  Standard CT scans fail to detect cancer until the tumorous nodes are bulging with cancer.

The early detection of lymph node metastases has become a much higher priority now that lymph nodes can be safely targeted with modern radiation.  In the past, with older radiation, side effects were excessive due to collateral damage to the intestines.

 

At Prostate Oncology Specialists we have had reasonably good results imaging lymph nodes with C¹¹ acetate PET scans performed by Dr. Fabio Almeida in Phoenix.  Also, Choline PET scans have been used with success at the Mayo Clinic. However, even with PET scans there needs to be minimum amount of tracer present in the lymph node before it reaches the threshold of detectability. Therefore, PET scans may be unable to detect metastatic nodes until the cancerous nodules are more than 6 mm in diameter.  Studies evaluating intravenous Combidex in conjunction with MRI scanning indicate that normal lymph nodes can be distinguished from metastatic nodes even when the metastases are as small as 3 mm. In one study comparing Combidex with Choline PET scans, Combidex was more accurate at detecting metastatic nodes.

 

I am raising the matter of Combidex in this blog because now, for the first time in years, Combidex has become commercially available again in Europe.  Dr. Jelle Barentsz from the University in Nijmegen has been able to purchase all rights to Combidex along with all the documents and files from the original manufacturer. Unfortunately, as yet there are no sites in the United States that offer Combidex.

 

More than 50,000 men annually develop a cancer relapse after surgery or radiation.  A relapse is indicated by the presence of a rising PSA level in the blood. The rising PSA signals that cancer is present, but offers no indication about the location of the cancer in the body. New scans such as C¹¹ PET and Combidex-enhanced MRI have opened up a whole new realm of treatment possibilities. After all, if the cancer can be located, it creates a possibly for cure by targeting it with radiation.

 

We welcome the renewed availability of Combidex, thanks to the concerted efforts of Dr. Barentsz.

READ MORE ON COMBIDEX

Past Blogs by Ralph Blum
http://prostatesnatchers.blogspot.com/2012/11/life-after-combidex-part-1.html
http://prostatesnatchers.blogspot.com/2012/11/life-after-combidex-part-2.html
http://prostatesnatchers.blogspot.com/2012/12/blog-post.html

Latest PCRI Insights written by Jelle Barentsz, MD
http://prostate-cancer.org/detecting-lymph-node-metastases-combidex/

 

Life After Combidex (Part 1)

BY RALPH BLUM

A few days ago I got an email bemoaning the demise of Combidex, and asking for a review of the situation, including what replacements were on the horizon. So in this Blog and the next, I will attempt to shed some light on the matter.

The most common areas of prostate cancer metastasis are the pelvic or abdominal lymph nodes and the bones, but detecting whether the cancer has spread to the lymph nodes is a problem, because no truly reliable diagnostic test for lymphatic involvement is currently available.

In 2007, when my Gleason score had gone from 6 to 7 and the cancer had arrived in the left seminal vesicle, I traveled to the Netherlands for a Combidex MRI. According to the makers, Advanced Magnetics, Inc. (now AMAG Pharma), Combidex, the brand name for ferumoxtran-10, could “assist in the differentiation between metastatic and non-metastatic lymph nodes in patients with confirmed primary cancer who were at risk for lymph node metastasis.” How it worked was that metastatic lymph nodes showed less “uptake” of the iron oxide nanoparticles. Fortunately for me, all my lymph nodes were clear. However (and it’s a long story that I detailed in Invasion of the Prostate Snatchers) the Combidex infusion MRI, by far the most reliable (better than 90% accurate) diagnostic test for lymph node detection, didn’t make it past the FDA watchdogs, and AMAG Pharma discontinued the production of ferumoxtran-10. So the Combidex MRI is presently no longer available anywhere.

The primary FDA-approved diagnostic test for detecting lymphatic involvement is the ProstaScint scan. Given by an intravenous injection, ProstaScint circulates throughout the body and attaches to prostate cancer cells. The injection contains a small amount of low-level radioactive material that is absorbed by the cancer cells and shows up as “hot spots.” But the findings are subtle, with a high risk of false positives, and an absolute necessity with the ProstaScint scan is an extremely experienced interpreter.

Meanwhile in Holland, Dr Jelle Barentsz, Professor of Radiology, UMC  St. Radboud,  Nijmegen, has been working on a validation study of Feraheme (made of nano-particles of iron) as a lymph node diagnostic agent. Feraheme is the contrast agent with which AMAG Pharma replaced Combidex, and Dr. Barentsz’ study is to find out if Feraheme is as good a contrast agent as Combidex. Currently Feraheme is only approved for treating patients with iron deficiency anemia or chronic adult kidney disease.

We desperately need better tests. The ability of oncologists to accurately detect lymph node involvement could signify a huge step forward in staging and, therefore, in making optimal treatment decisions for men with newly diagnosed and advanced prostate cancer.

Harmony & Spirituality Practice Cultivating “Wa”

BY RALPH BLUM

Many years ago, I was invited to attend a breakfast fund raising event at the Bel Air Hotel in West Los Angeles. Ted Turner was attempting to squeeze donations from a room full of Hollywood moguls. The private dining room was filled with sunlight, and I remember sitting there, bored, zoned out and forking segments of my eggs Benedict around, when Turner’s Savannah chain gang growl poked a hole in my reverie: “I tell you, it’s spiritual,” he exclaimed. “And you know how I know it’s spiritual? Because I paid cash money for it.”

To this day, I have no idea what “it” was. But Turner’s logic—his working definition of “spiritual”—made me smile and stuck with me to this day. And while I’d rather steer the long way around when it comes to spiritual matters in general, I have become a devoted fan of harmony, as in feeling at peace. What the Japanese call Wa. Bottom line: I try not to regret anything that has already happened, and not to worry about what might happen. And in a way, I think this has played a role in my coming to terms with prostate cancer.

When discord hobbles me, throws off my vital signs, fogs up my reasoning, I feel it has a definite impact on my immune system. Efforts to counter mindless anxious behavior through breathing and light meditation may help, but in my case, only minimally. Instead, whenever I encounter discord, or more to the point, when I catch myself creating or contributing to the dissonance, I retreat from that discord as fast as I can. This happens in three steps:

First, I catch myself, recognize what’s happening, mark the moment: Blum, you’re doing it!

Second, I apply the brakes, stop what I am doing as best I can. Do whatever it takes to get into reverse and back away. I think of this step as “circuit breaking.”

Third, I substitute different behavior, consciously find a better way to look at what is disturbing my peace and serenity, my wa.

Example: Despite my expectations, my PSA has risen. And I’m suddenly scared s—tless my next Gleason score will have deteriorated from 3 + 3 to 3 + 4, and that I will start feeling pressure to “act,” to begin radical treatment. As a Remedy, I hold a conversation with myself,

Me:  How many years has your cancer been in the seminal vesicle?
Myself: About six.
Me: So six years out of the capsule?
Myself: Yup.
Me:  Is the cancer in your bones?
Myself: No.
Me: Well, how about the lymph system?
Myself: Don’t think so.
Me: So And how old are you?  

Myself: I’ve been around the sun 80 times.
Me: So in 10 years you’ll be 90?
Myself: You might look at it that way.
Me: And your cancer, basically untreated, has been stable for almost a quarter of a century.

Myself: Something like that.

Myself: So given hour history, what kind  of prognosis would you expect for the years to come. . . ?

The Q and A continues until I find myself relaxing, counting my blessings. This sounds like pretty simple-minded stuff. But not getting caught in the quicksand of negative emotions or behavior that is toxic, just staying in the “here and now,” is a spiritual practice that helps maintain Wa. I do my best to stay in the present moment. But when I slip, ASAP after the fact I review what has happened. I replay what happened in my mind with different features, focus on a better way to handle it next time. And some day perhaps I’ll find out what spiritual stuff Ted Turner paid cash money for. And place an order for myself. A baseball team. An ocean going racing yacht. A date  withJane Fonda. CNN. A day at the beach. . .

To each his own kind of Wa.

More to come.