There are a number of things concerning Invasion of the Prostate Snatchers of
which I am proud. Two in particular stand out.
First, that despite his full and demanding
schedule, Mark Scholz and I were able to collaborate effectively to produce
this book. I have received a whole
heap of emails from men thanking us and pointing out that, as far as they know,
it is the first time in the literature on prostate cancer where the voices of
doctor and patient were heard speaking as peers, each presenting those aspects
of the disease he considered of primary importance to the newly diagnosed.
Second, it was both surprising and gratifying
to learn that Snatchers had been
awarded the 2011 Nautilus Book Award Gold Medal for “Conscious Media and
Investigative Reporting” as the result of our tracking down the FDA rejection
of Combidex. Since many of you have not read our book, and I know of no other
readily available report on that destructive process, I want to review it here
as part of the Combidex story.
I was determined to find out
why the FDA had rejected Combidex back in 2005. I started by tracking down
Jerome Goldstein, the former CEO of Advanced Magnetics (Ad Mag), the Cambridge,
Massachusetts company that had marketed Combidex. I found him through his golf
club, the Country Club in Brookline.
“So what do you want to know?” Goldstein asked.
“What went wrong? Why did the FDA reject Combidex? And can I
quote you?”
“I’m retired now,” Goldstein said in a gruff voice. “so I
suppose you can quote me.
Some of the blame was ours. Our
application was too broad. We should have gone for disease specificity. But
that’s only part of it. The FDA bureaucrats in ODAC were also to blame.
ODAC—that’s the Oncologic Drugs Advisory Committee—has total control over the
life and death of every new drug application. And because of ODAC’s decision, prostate
cancer patients are dying and suffering needlessly.”
Ad Mag’s fatal error was that
instead of specifying Combidex as a contrast agent for establishing lymph node
involvement in one type of cancer—prostate
cancer—they had tried to broaden its application to cover all cancers. They
should have known better. Once it has FDA approval for a single “indication,” it
is legal for doctors to use a drug “off label,” meaning, wherever, in their
judgment, it is useful.
I asked Goldstein if it was
possible to obtain a transcript of the ODAC meeting, and he told me that their
meetings were a matter of public record. Then, in a low angry growl, he said,
“Nobody should ever die from this disease. It’s a crime.” I was about to hang
up, when he said, “You know I have prostate cancer. I was diagnosed two years
ago. Gleason 6. My internist said I should do surgery or put seeds in.”
“So what did you do?”
“Nothing.”
“Nothing?”
“Well, not exactly nothing. I bought a new putter.”
Although the transcripts of FDA meetings are a matter of record, they are not that easy to find. What’s more, they are not indexed so you have to dig. When I finally read the minutes and watched a video of the March 3, 2005 ODAC meeting, it was painfully obvious that there was plenty of blame to go around. But the way Combidex—NDA Application 21-115—went down really pissed me off.
ODAC found lots to attack. One
patient went into anaphylactic shock from the Combidex. They delivered CPR and
epinephrine, but it was too late: the man died at the hospital thirty-five
minutes later. The fact that this single death had occurred a decade earlier,
and had resulted in an immediate shift in method of delivery—from injection, to
dilution of the contrast agent in saline and use of slow infusion—did not
reassure the FDA. When I went through the Combidex records, I learned that the
man who had died was so eager to participate in the trials that he failed to
disclose his allergic condition, or that he had gone into anaphylactic shock on
other occasions. Ad Mag pointed out that the vast majority of test subjects had
only very minor and transient adverse (mainly allergic) reactions and that only
four out of 1,236 patients had experienced a more serious adverse reaction.
There had been no further deaths and no serious side effects.
After interviewing several staff members at Ad Mag, I became very aware of the financial reality. Contrast agents are not economically viable. Subjected to all the same requirements as a drug, a contrast agent like Combidex can cost over $100 million to develop, and the likelihood of FDA approval is increased by having a narrow indication. But here’s the irony: the narrower the indication, the less chance the company will ever recoup its money.
And there is a fundamental
problem with imaging substances in general. Contrast agents are regulated just
like drugs: the same standards apply for a contrast agent as for an antibiotic
used to treat a life-threatening infection. Apparently it takes an act of
Congress to get contrast agents regulated differently from drugs, and so far
that hasn’t happened. But it’s obvious that there need to be different rules
for approving imaging agents. Just another disgrace. Add it to the list.
What a crock! A normal lymph
node for somebody with breast cancer is no different than a normal lymph node
for somebody with prostate cancer. Combidex is “taken up” only in normal
tissue. If the tissue’s not normal, the contrast agent is not taken up, and you
know there’s cancer.
So while it would appear that
applying for a broad application not only made medical sense, it was the only
hope Ad Mag had of getting their money back.
There’s a lot more to the death
of Comidex. You’ll find it in two chapters of our book: Chapter 15, “Now
Playing for a Limited Time Only: The Combidex Follies,” and more in Chapter 17,
“Anatomy of an Assisted Suicide.”
I admit it. I’m pretty much
obsessed with the fate of Combidex. But as some French person once said, Rien ne vaut un bon obsession . . . (“There’s
nothing as valuable as a good obsession.”) And now I’ve found an ally (See
prior Combidex blogs) in the
courageous Prof. Jelle Barentsz
Combidex redux!
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