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.