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For many years now I have been hearing asbestos company
lawyers argue "that there is no medical benefit to the early detection of malignant
mesothelioma." Below is an excerpt from a speech recently given by a prominent
asbestos company defense lawyer at an asbestos lawyers conference in Boston. To quote:
"No studies have
been done which establish any benefit to finding pleural or peritoneal mesotheliomas at an
early stage. The ‘evidence' is largely anecdotal and varies widely from one
individual to another. Because the tumors are typically found only after they have spread,
and are incurable even if they are discovered while the patient is symptom-free, early
detection has virtually no medical benefit."
The statement is disturbing for a number of
reasons.
First, there is something ghoulish about
a lawyer for a company that has poisoned people advocating that there is no need to
monitor the health effects caused by their poison. The attitude seems to be: yes, we made
a poison that invaded the lungs of many innocent people, but there's no proven way to
combat or prevent the bomb from exploding, so let it be and let us alone. Doctors have a
duty to "do no harm." I wish lawyers were guided by the same credo.
Second, the statement is debatable at
best and misleading at worst (see below). There may not be any definitive studies out
there which establish a clear benefit, but there are plenty of studies which affirm that
early detection is vital because it allows the patient to choose from more treatment
options. At the "individual" level, what is more important to the patient than
having the power to select from multiple choices? Drs. Sugarbaker, Pass, Rusch et al have
published articles which support the thesis that certain MM patients have a better
prognosis when diagnosed early and treated by multi-modal therapy -- and few doctors will
recommend extrapleural pneumonectomy or pleurectomy/decortication if the tumor has
trespassed the visceral pleura into the mediastinum, diaphragm, and/or lymph nodes.
Third, the "incurability"
argument is tainted by conflict of interest. The asbestos companies have shelled out
millions of dollars to disprove that asbestos causes cancer, but they have not spent a
dime to find a cure. In this world, you have to give action to get action. A wrongdoer has
a duty to mitigate the damage he inflicts. Instead of paying high priced lawyers to excuse
their misconduct, they ought to be funding research on finding tumor markers, vaccines,
immunotoxins and other therapies. AIDS was also considered "incurable" ten years
ago. Now, after millions have been spent to find a cure, AIDS patients have a real chance
at survival. Same for breast cancer.
Fourth, the "incurability"
argument hinders the ability of patients to obtain aggressive and innovative therapy.
Insurance carriers these days are exceedingly reluctant to cover any medical procedure
that is considered "experimental." There are a handful of surgical oncologists
in this country who are truly dedicated to helping mesothelioma patients survive and find
a cure. I have had clients who arranged to meet with these experts, but at the last moment
their insurance carrier denied coverage and ordered them to see a non-expert who offered
only palliative care or no care at all. The HMOs are still entrenched in the "death
management" mind set for mesotheliotics. This is a vicious circle -- there won't be a
cure if we don't fund the research and without the research the insurance industry will
continue to refuse to cover innovative therapies. It's also a tragedy.
Fifth, the consensus among the doctors I
correspond with is that if there are "no studies," it is because nobody has
every tried to create an early detection program, fund it, implement it, and publish the
results. Most mesothelioma patients are NOT detected in the early stages -- sometimes
because general doctors fail to read the signs. Moreover, it's not clear exactly what
"early stage" means, as even at Stage I a patient with a 1 cm tumor can have 500
million tumor cells active and growing. Most mesotheliomas -- approximately 80% -- can be
detected from CT scans and chest films, along with a clinical picture (weight loss,
shortness of breath, pain in shoulder, pleural effusion, asbestos exposure history).
Multi-modal extrapleural pneumonectomies are certainly expensive in dollar terms. The goal
should be to a find a cookbook variety screening test that would obviate the need for
"radical" approaches.
The key is to give people in high risk
populations (e.g., shipyard, steel mill, paper mill, petrochemical plant workers,
insulators) a choice. For example, Dr. Robert Cameron has discussed the possibility of a
"prophylactic ablation" for high risk patients. The idea is that mesothelioma
can only arise in malignant mesothelioma cells. What if we removed or destroyed all the
healthy mesothelial cells? A technique could be developed to use photodynamic therapy to
kill the mesothelial cells in the pleural space, or perhaps inject an anti-tumor drug that
would accomplish the same objective. This would remove the soil so to speak for a possible
tumor to grow. The pleural linings would bond together and the impairment if any would be
minimal.
Sixth, if we do nothing, we learn
nothing. If we don't invest the research dollars now and develop a wider range of
treatment plans down the road, we will never have a chance to find a cure. I think history
has taught us that with enough money, we can put a man on the moon. It takes will and it
takes money. The best and brightest are humming with great ideas for gene therapy,
immunotherapies, tumor-killing viruses, vaccines, "angiostatins and endostatins"
(which purportedly kill tumors by starving their blood supply), interferon and PDT. In
talking with doctors like Dr. Cameron and Dr. Jablons, there is a real excitement over the
possibility that good therapies can be developed. But without a serious financial
commitment at the basic science level, doom and gloom will be a self-fulfilling prophecy.
We cannot rely on private enterprise to get it
done. The drug companies are driven by profits. They are not willing to invest the
millions of dollars it takes to develop and test a new drug when "only 4,000"
Americans die each year from mesothelioma. They look at the statistics. The conventional
thought is that in 30 to 50 years the incidence of disease in America will be negligible
(what about the rest of world where asbestos is still being mined, milled and used?). They
are not willing "to fire up the vats" without better prospects of an upside.
This is not a money-making proposition. It's about doing the right thing. That's why we
should first look to the companies who are responsible for the disease -- the asbestos
companies -- and secondly to the US Government, who allowed the companies to peddle their
poison for far too long before issuing its ban in the 1970s.
Since the tortfeasors have refused to
voluntarily clean up their mess, the solution is legislation. Congress ought to force the
asbestos companies to pay a surplus of every settlement or jury verdict dollar to a
research foundation. The government should match each dollar. The money can be managed by
a blue chip team of the best mesothelioma doctors, doctors like Dr. Pass, Dr. Cameron, Dr.
Sterman, Dr. Jablons, Dr. Taub, Dr. Ruckdeschel, Dr. Sugarbaker, Dr. Rusch, Dr. Robinson
and Dr. Hammar.
Towards this end, my firm by the year 2000 hopes
to establish a Mesothelioma Research Foundation. The goal of the Foundation will be to
fund basic science and clinical research in order to help expand the treatment options
available to mesothelioma patients. My first step will be to ask the asbestos companies to
come forward and pay their share. Next, I will ask our political leaders to fashion a
legislative solution. Along the way, I will ask the plaintiff's bar for contributions.
The money is available. It's a question of will.
The tobacco companies just "invested" $40 million in television commercials to
combat proposed state and federal legislation that would have hindered their ability to
sell more cigarettes. We need to get started. We have known -- including the US Government
-- that asbestos causes lung cancer since the 1940's. Here we are, almost 60 years later,
and still the medical community has largely a fatalistic attitude about mesothelioma.
We need to get started! It generally takes about
15 years to bring an experimental drug out of the laboratory and into human patients. Only
one in 1,000 compounds tested makes it into clinical safety trials in humans, and only one
in 20 of these are eventually approved by the FDA.
What's out there now? There is a phase III
protocol using Onconase, but I have not read anything truly uplifting (I wish I was
wrong). I have heard about a drug made by Bayer that is being tested with other
chemotherapy agents in Rochester, MN and San Antonio, Texas. The drug is called BAY
12-9566. The drug apparently had a favorable response in a mesothelioma patient in a phase
I study for a wide range of cancer patients (it is not confirmed that the subject actually
had mesothelioma). Bayer is considering the idea of developing a "compassionate use
program" for mesothelioma patients. The drug will be tested in phase I trials for
pancreatic and small cell lung cancers in 1999. We encourage Bayer to open up the studies
to mesothelioma patients and hope that they will publish the results of their phase I
trials soon.
I sent the quote from the
asbestos company lawyer to several doctors who diagnose and treat mesothelioma patients.
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Dr. Samuel Hammar,
Pathologist
Diagnostic Specialties Laboratory, Inc. Bremerton, Washington
Dear Mr. Worthington:
I am responding to your letter concerning
"No Medical Benefit to Early Detection of Mesothelioma." In general, I do not
agree with that statement but would state that it is difficult to detect mesotheliomas at
an early stage of the disease at the present time. If one could devise a test in which you
could identify mesotheliomas when the tumors were in stage 1 or less in the anatomic
staging scheme, I think that would potentially result in more therapeutic options for
patients with mesothelioma. I am convinced that there are a group of patients with stage 1
mesotheliomas, especially epithelial mesotheliomas, that significantly benefit from
extrapleural pneumonectomy or from radical parietal pleurectomy and visceral pleural
decortication.
I am also of the opinion that as time goes on
the biology of mesothelial cells will become better understood which could lead to a test
in which mesotheliomas could be detected at a very early stage, specifically, a stage
before they became clinically detectable. What I have often wondered about in
mesotheliomas is whether a platelet-derived growth factor, a factor produced in 1/4 - 1/3
of patients with epithelial mesothelioma could be used as a way of early detection. It is
not clear to me at what point in time this growth factor appears, but if it could be
detected at a point where the tumor was not grossly visible or a point where the tumor was
just beginning, maybe it could be used as a marker of when a patient should be given some
type of therapy which might include chemotherapy, radiation therapy or photo-ablative
therapy.
The problem, as I see it, is that at the present
time relatively few cases of mesothelioma are detected at an early stage. This is probably
due to the fact that it take a significant amount of tumor to produce clinical symptoms
and because mesothelioma is not like a lung cancer that produces a nodular mass and is
therefore difficult to detect in standard radiographs or CT scans. I am one who thinks
that once a mesothelioma progresses past anatomic stage 1 there are no treatment
modalities that can halt the growth of that tumor. When this occurs it is my opinion that
more effort should be spent in trying to keep the patient pain free than trying to cure
him.
I would like to see more studies done at trying
to detect tumor markers of mesothelioma (perhaps serum markers) in people who were exposed
to asbestos that would result in the tumors being detected at a stage before they were
clinically apparent. If that was done, maybe those patients could be treated in a way that
resulted in a significant survival rate.
There are antibodies that are now being
developed against certain cancers, specifically lymphomas that seem to be able to cure the
diseases in a very short period of time with only minimal side effects. If a tumor marker
for a mesothelioma was found that was highly specific, I could envision the same type of
therapy working in mesotheliomas, specifically an antibody tagged to radioactive iodine
that would search out the mesothelial cancer cells, attach to them and then kill them. As
in lymphoma, you would have to have something absolutely specific for cancerous
mesothelial cells that would do minimal harm to the normal mesothelium and to the body in
general.
Sincerely,
Samuel P. Hammar, M.D.
November 2, 1998
Dr. John C. Ruckdeschel
H. Lee Moffit
Cancer Center, Tampa, Florida
Dear Mr. Worthington:
The statement that there was no benefit to early
detection is technically accurate, however, it is misleading. Very few centers treat
mesothelioma and there is very little existing literature codifying the long-term survival
of patients with surgically treated disease. All of us who are active in treatment of the
disease know that if it is found in a resectable state, that a portion of those patients
will be cured by an extrapleural pneumonectomy. However, there have been no studies to
date testing any technique for this. I know that many of the former patients are under
regular study, but have nor seen any of the follow-up data on this serial analysis. As you
are painfully aware, these patients are mostly diagnosed late.
Consequently, I don't think there is any strong
evidence to refute the concept other than the common sense fact that the only curable
patients are those that we do find early. Best wishes.
Sincerely,
John C. Ruckdeschel, M.D.
Professor of Medicine and Center Director
November 9, 1998
Dr. Robert Cameron
UCLA Medical School, Los
Angeles, California
Dear Roger:
The absolute statement about no benefit to early
detection is technicallly true. No one has ever shown any benefit to early detection (of
course no one has ever really tried and mesothelioma once present is almost always diffuse
and for the most part currently rarely curable.).
However, a recent patient brings up an
interesting sideline to this. If patients are known to have high asbestos exposure, i.e.,
worked for Johns Manville for 20 years, etc. does prophylactic removal of the pleura
PREVENT mesothelioma? This also has not been answered but makes sense in patients who are
at particularly high risk as "an ounce of prevention is worth thousands of pounds of
treatment."
Therefore in screening patients, perhaps high
risk individuals should undergo prophylactic pleurectomy to prevent the need for treatment
of an normally incurable disease. If we can develop new treatments (by the way, Bayer has
a new drug which looks promising although it has been used in only one patient so far and
we are looking into doing more with it) then screening may become more important. Sorry I
cannot refute the other lawyers statement any better but unfortunately, we have not done a
good job at scientifically proving him wrong!!
Robert Cameron
November 18, 1998
Note: Dr. Cameron and his team of
doctors/scientists at UCLA are working on an experimental IL-4 toxin, as well as new
angiogenesis inhibitors, which UCLA hopes to put into clinical trials in the next year or
so. They are also hoping to obtain the Bayer anti-enzyme. Dr. Cameron performs the
pleurectomy/decortication procedure. His strategy is to preserve a healthy lung because of
the probability of recurrence in the other pleural cavity. He compares the EPP to a
radical mastectomy, which is no longer in favor.
Dr. Robert Taub
Columbia Medical School, New York City
The statement needs to be analyzed. It seems to
refer to the inadequacy of current methods of screening of high-risk populations for early
detection of mesothelioma; parallel arguments exist for lung cancer. It may also be
referring to the observation that surgery alone has not made a statistical impact on the
overall survival of mesothelioma patients.
This, however, is to be clearly distinguished
from what happens in individual cases who are diagnosed with tumor that is confined to a
small, operable area. Mesothelioma, bad as it is, is not synonymous with a death sentence
because not everybody with the disease dies from it; we need to focus upon those who
don't. Now that operative mortality is down to 6% or less, we should not dismiss the
intuitive likelihood that selected patients who are both asymptomatic and operable and
that have their tumor extirpated have a better chance of living than if their tumor is not
removed.
Also, the reports of long term survivors after
multimodality (surgery, chemo, radiation) treatment is encouraging. Thus, for individual
patients right now, we need to find our how best to identify those patients who have the
best chance of falling on the "tail" end of the survival curve.
Dr. Robert Taub
November 1, 1998
Dr. David Jablons
UCSF/Mt. Zion, San Francisco, California
Roger:
We need to have a grass roots movement and like
all things we need to get some grant money to fuel the science to find a cure or at least
better therapies, early detection, etc.
It can and will be done. Let's make this happen!
There is plenty of money in these settlements and in the industry or through legislation
such that a small percentage (which would represent a major increase over current funding)
could be directed into research.
Best,
David Jablons
November 1, 1998
Abstract provided by
Dr. Lary Robinson:
Eur Respir J 1998 Oct; 12(4):972-81
Malignant pleural mesothelioma.
Boutin C, Schlesser M, Frenay C, Astoul P
Dept of Pulmonary Diseases, Hospital de La
Conception, Marseille, France.
The incidence of malignant pleural mesothelioma
(MPM) has risen for some decades and is expected to peak between 2010 and 2020. Up to now,
no single treatment has been proven to be effective and death usually occurs within about
12-17 months after diagnosis. Perhaps because of this poor prognosis, early screening has
incited little interest. However, certain forms may have a better prognosis when diagnosed
early and treated by multimodal therapy or intrapleural immunotherapy. Diagnosis depends
foremost on histological analysis of samples obtained by thoracoscopy. This procedure
allows the best staging to the pleural cavity with an attempt to detect visceral pleural
involvement, which is one of the most important prognostic factors. Although radiotherapy
seems necessary and is efficient in preventing the malignant seeding after diagnostic
procedures in patients, there had been no randomized phase III study showing the
superiority of any treatment compared with another. However, for the early-stage disease
(stage I) a logical therapeutic approach seems to be neoadjuvant intrapleural treatment
using cytokines. For more advanced disease (stages II and III) resectability should be
discussed with the thoracic surgeons and a multimodal treatment combining surgery,
radiotherapy and chemotherapy should be proposed for a randomized controlled study.
Palliative treatment is indicated for stage IV. In any case, each patient should be
enrolled in a clinical trial.
Dr. Harvey Pass
Karmanos
Cancer Institute and Wayne State University, Detroit, Michigan
Dear Roger,
I agree with the message that you are trying to
convey on the net regarding the earlier detection of mesothelioma. In order to accomplish
this, however, there will need to be a collaborative effort uniting bench work and
clinical efforts between institutions which have (1) an interest in the disease (2)
ongoing expertise, not only clinically but at the bench and (3) insight.
For this disease, one needs a consortium of
centers which will develop a multitude of Phase I-III trials, establish a tissue bank, and
meet on a regular basis. Serum, lymphocytes, tissue all need to be banked with the
patients permission prospectively. Its a huge effort and logistical challenge.
It is encouraging that this issue has stirred so
many hearts.
HP
December 1, 1998
*** POSTED NOVEMBER 30, 1998 ***
Defense Lawyer's
"No Benefit" Theory Promotes Doom and Despair, Dr. Corey Langer, 12/23/98
I recently received your letter dated 10/30/8
regarding the potential benefit of early detection of mesothelioma. My reply follows:
To date, no randomized studies adequately
address this issue. The ideal trail would randomize early stage mesothelioma patients to
best supportive care of palliative unimodal therapy vs combined modality surgery and
chemotherapy with or without radiation. However, the absence of trials proving benefit
does not constitute proof of the converse: that early detection and diagnosis yields no
benefit. Sugarbaker and colleagues reviewed results of multimodal treatment in 94
consecutive patients (PROC ASCO, Volume 14, March 1995, A-1083), and reported their
findings at the American Study of Clinical Oncology Meeting in 1995. Treatment consisted
of extra-pleural pneumonectomy, postoperative chemotherapy (CAP regimen) for at least two
courses and XRT (45 Gy). Mean age was 54. Patients had either stage I or II disease (JCO
11: 1172-1178, 1993). Median survival was 21 months, and overall survival at two years
48%, considerably better than instonic controls. In addition, the five year survival rate
exceeded 20%. This sort of approach obviously needs to be compared to either surgery alone
or chemotherapy alone, but such an effort would require international cooperation.
While early pleural mesothelioma can potentially
be detected early, peritoneal mesothelioma generally defies early detection. Such patients
usually present with abdominal distention +/- ascites. Even here, aggressive surgical
debulking followed by interpertioneal therapy may lead to long term survival benefit (CJ
Langer, J of Surg Oncol., 60:100-105, 1995).
The contention that earlier detection yields
absolutely "no medical benefit" is misguided and potentially harmful. It
cultivates and spreads the prevailing ethos of therapeutic nihilism that unfortunately
imbues both the medical and legal communities.
I hope my answers prove helpful.
Yours truly,
Corey J. Langer, M.D.
Attending Physician
Medical Oncology |
*** POSTED DECEMBER 23, 1998
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