The below article from the Oncology Times medical journal, was authored
by Dr. Andrew D. Lawson, FRCA, FANZCA, MSC, a consultant in Intensive
Care, Pain Management and Anesthesia in the UK and Australia and an Honorary
Senior Lecturer in Medical Ethics at Imperial College in London. Dr. Lawson
was diagnosed with malignant pleural mesothelioma in 2007 at the age of
47. Following his diagnosis, Dr. Lawson read every publication he could
find about mesothelioma and discussed available treatments with colleagues
from a variety of disciplines.
In the article, Dr. Lawson expresses concern and anger over the way many
doctors view treatment for mesothelioma and other terminal illnesses.
He laments the position shared by many doctors that: “It has been
deemed that nothing works, so the best thing to do is to use us as subjects
in clinical trials.” He states that this position “ignores,
however, the individual patient and starts from the position that you
must have an RCT [randomized clinical trial] in order to use a treatment.”
He, instead, concludes that, especially in cases where the prognosis is
less than one year, “therapy cannot wait for trials to be conducted”
and that “the moral duty to treat may trump the notion of scientific
Dr. Lawson describes how, on the very day he was diagnosed with pleural
mesothelioma, his doctor recommended that he enroll in a randomized clinical
trial involving the
Extrapleural Pneumonectomy surgical procedure. Before agreeing to participate in the trial, Dr. Lawson’s
own research led him to an article in theAnnals of Surgical Oncology authored by thoracic surgeon Dr. Robert Cameron. Dr. Lawson states that,
after reading this article, “whatever reservations I had about EPP
were confirmed” and that “not surprisingly, I chose not to
go down that route.” He notes that others he knows in the field,
including senior doctors, also advised him not to have an EPP.
Dr. Lawson goes on to compare participation in the EPP clinical trial to
being “sacrificed on the altar of evidence-based medicine”
and questions whether informed consent for EPP could exist without reading
Dr. Cameron’s article along with one supporting the surgery.
We believe that Dr. Lawson’s article is a must-read for any patient
who is contemplating EPP.
Speak Up: Reflections from a Nightmare Patient - Me!
In BMJlast summer, Prof Kieran Sweeney published a moving piece about his journey
as a patient with Mesothelioma. I agree with many of his thoughts and ground rules regarding how we as
a profession should deal with patients with such an appalling prognosis.
It is true that there seems to be little that can be done for patients
with mesothelioma; many of whom feel left alone in what Professor Sweeney
called the kingdom of the sick.
I, like he, also have been diagnosed with malignant pleural mesothelioma.
Mine was diagnosed when I was 48 in 2007. Of the three doctors that I
know of who trained at Guy's Hospital in London who have contracted
the disease, I am the only one still alive. Prof Sweeney died on Christmas
Eve 2009; he made some helpful comments on this piece prior to that, so
I'd like to dedicate this to his memory.
I too have experienced some insensitivity along the way. Perhaps the radiologist
who rang me up at home to tell me my CXR showed I had cancer and would
I like to come in for a CT could have been a bit more subtle.
The most farcical incident, though, was when I was having a pleural biopsy.
I have been there with piles of opened kit and nothing quite fitting,
when putting in Hickman lines myself. We all know the scene; piles of
paper wrapping, discarded syringes etc. It's no problem when you have
an anesthetized or sedated patient. I, however, was fully conscious, with
my wife (a forensic physician) looking on in horror. Call me old fashioned,
but when a patient says, “Do you know that as a consultant anaesthetist
of some years, I have always found it is helpful to wait for the local
anaesthetic to work,” the response should not be to just push harder!
My wife and I agreed afterwards that a video of the whole procedure, particularly
the bit with the three registrars (interns) with their backs to me staring
at the ultrasound machine and fiddling with knobs, would make a great
example of how not to do something, especially to a colleague
Diagnosis Established, Now on to Treatment
Diagnosis established, I moved on to treatment. I was treated with Alimta
and cis-platinum, which suddenly midway 2007 became officially available
on the NHS in England. It has always amazed me how drugs can suddenly
become more cost effective after publicity or high-profile cases. One
moment it's not worth a QALY, and then it is; it must be that level
one evidence, politics!
Like Professor Sweeney, I have researched my illness. I see every paper
published on Medline on mesothelioma. I have read all the abstracts from
the international Mesothelioma Interest Group meetings, and I discussed
my treatments with many colleagues from a variety of disciplines. I suppose
I am the nightmare patient.
My concern and, to some extent anger, is focused on how some in my profession
view treatment for this terrible disease, you have your chemo and or surgery
and that is it. I accept that concepts of redistributive justice place
constraints on treatments, but as will be seen, I merely augmented my
treatments with relatively inexpensive drugs already on the market for
other illnesses. Other patients who asked for these were refused
My surgeon alerted me to the putative effect of bisphosphonates on mesothelioma.
IV bisphosphonates have been shown to have an inhibitory effect on mesothelioma
cells in a mouse model in vitro and in vivo. I corresponded with the researcher
in Alabama and was interested in the model. I mentioned this to an oncologist
whom I used to see. The reply was, “You can't do that; we won't
know whether the chemo has worked.”
There is not much more to say. I changed oncologist, and, of course, I
have had IV bisphosphonates. Why? Because there is a plausible biological
rationale for their use, a known side-effect profile, they are available,
and apparently I was going to die.
What possible, sustainable, cogent, and moral reason could a physician
looking after me have for not agreeing to my request? Or indeed, not suggesting
it in the first place? Is it because the prognosis is so poor that data-gathering
has become the principal activity of some doctors treating not just patients
with mesothelioma but anybody?
It has been deemed that nothing works, so the best thing to do is to use
us as subjects in clinical trials. This is a perfectly respectable consequentialist
argument. It ignores, however, the individual patient and starts from
the position that you must have an RCT in order to use a treatment.
Indeed on the day of diagnosis it was suggested to me that I might enroll
in the MARS (Mesothelioma and Radical Surgery) study—the surgery
being extrapleural pneumonectomy (EPP).
Of course some patients might acquiesce, even accepting the very high morbidity
rate and a not inconsequential mortality rate. The question is how many
would accept surgery of this kind in a trial or otherwise if they were
then handed this quotation from an internationally respected surgical
“EPP should not become the [Sir Edmund] Hillary operation of thoracic surgery:
being done simply because it is there and it can be done.”
Or this from the same article:
“It is clear that if nothing else, one should learn from history and not
make the same mistakes. The history of radical surgical procedures is
littered with abandoned operations.”
Clearly the investigators were trying to tease out evidence from a very
cluttered field, a laudable aim. I found the journal article quoted using
a web search and whatever reservations I had about EPP were confirmed.
Could informed consent for the procedure exist without having read this
article as well as the one supporting surgery? I am not sure.
Not surprisingly I chose not to go down that route. What is worrying is
that people I know in the field, and other senior doctors also privately
advised me not to go down that route. This is a sad truism in medicine;
we frequently will not have done to us what we do unto others.
In Prof Sweeney's article there is a physician's perspective in
which an oncologist states that randomized trials “show little evidence
of survival or quality of life benefits”—true. However what
does this undoubted fact mean for patients like me? The implication being
that, as the RCTs do not show much, then there really is nothing that
can be done
How to Deal with Suffering & Illness in the Face of Uncertainty?
Here is a key question, though: How do doctors make a decision about how
to deal with suffering and illness in the face of uncertainty? It seems
to me that the profession has thrown up a defensive barrier of scientific
orthodoxy, the RCT, behind which we can retreat when we seem to have nothing to offer.
Because RCTs have shown little if any benefit, then the oncologist states,
“the role for active supportive care is paramount.” Should
I accept just active supportive care (do they do inactive supportive care,
a sort of supportive care lite?)? Should it be paramount?
Supportive care is thus more important than an attempt at treatment. Do
I accept this? No. Should patients accept this? I would not advise it.
I say this not as a criticism of the oncologist but of a system that seems
at times to have lost view of our core raison d'être.
As the GMC (General Medical Council) puts it, “Make the care of your
patient your first concern.” Nowhere in the GMC guidelines does
it state that in the absence of an RCT you should not actively treat the
disease to the best of your ability. I accept that concepts of redistributive
justice place constraints on treatments but as will be seen I merely augmented
my treatments with relatively inexpensive drugs already on the market
for other illnesses. Other patients who asked for these were refused.
The problem lies with what we accept as evidence, as Sackett et al said:
“Some questions about therapy do not require randomized trials (successful
interventions for otherwise fatal conditions) or cannot wait for the trials
to be conducted. And if no randomized trial has been carried out for our
patients predicament, we must follow the trail to the next best external
evidence and work from there.”
I figured that, having had the best available chemotherapy; it was not
in my interests to hang around waiting for the next trial. Pain relief
is part of “active supportive care.” One of my doctors pointed
out that celecoxib (a COX-2 inhibitor) as well as being an analgesic might
have some anti-mesothelioma properties.
Here is quote from a paper in the
International Journal of Cancer in 2004: “In mice implanted with mesothelioma, celecoxib treatment
significantly increased average survival from 45 days to 62 days, the
researchers note, and there were three long-term (more than 120 days)
survivors among the treated mice."
Which Is the Honest Answer?
I am not troubled with pain from my tumor, but I do have a chronic shoulder
problem, so what analgesic do I use? Celecoxib, of course, and my question
to other clinicians is this: If you have a mesothelioma patient in pain,
then why not use celecoxib, other things being equal?
Or, to put it another way: If you do not offer it then why not? The Cochrane
database supports it as a single-dose analgesic for postoperative pain
(in comparison to ibuprofen), and the caveat for its long-term use in
rheumatoid arthritis is cost.
So do you say to your patients, there is an analgesic available that might
also affect your tumor progression, but we do not use it because it is
too expensive, or do you say there is no evidence? Which is the more honest answer?
IP Gene Therapy
Since the bisphosphonates, I went on to have intrapleural gene therapy
in Philadelphia (Hospital of the University of Pennsylvania—HUP
) in a Phase I study.
There is a tendency to bash US medicine in the UK; criticism of the lack
of coverage is I think quite justifiable, but from a personal point of
view I was very impressed, both by the efficiency as well as the sense
of can-do (or at least try to do!), in contrast to the nihilism I encountered
from some in the UK.
I had a mixed response to that treatment. Later when there was some progression
on CT/PET, my oncologist was happy to try metronomic cyclophosphamide
and gemcitabine to my regime on the basis of another basic science paper
and the knowledge that a Phase I trial was in the offing.
This regime seems to have produced a significant response. I am lucky to
be in the hands of a surgeon who supports my wish to try other things
prior to surgery, but who will operate if I request or the disease progresses
and an oncologist similarly concurs.
Moral Duty to Treat
In 2008 I gave a talk to a group from the Medical Research Council oncology
clinical trials unit. I suggested that in diseases with a very poor prognosis
such as mine, that the moral duty to treat may trump the notion of scientific
rigour, that biological plausibility combined with patient consent was
a sufficient mandate to treat.
One in the audience said that this would produce anarchy. Is this really
what our profession is most concerned with? Keeping everything ordered
and neat, our p values and powers just right? Looking for good and best
evidence is an ethical duty, but we do have duties to our patients. There
are ethical tensions between the quest for the gold standard of evidence
and the moral duty to care for patients—how do we decide which is
the more important?
If you have a prognosis of less than a year, then I would suggest that
therapy cannot wait for trials to be conducted—call me just a tad
cynical, but I guess an oncologist with mesothelioma might agree.
When HIV was running riot in the early ‘90s nobody waited for an
RCT to treat. Why? The patients were dying, they had a voice, and the
physicians looking after them were doing just that—looking after them.
I accept that my future is bleak, that in all probability I shall die sooner
rather than later from this disease, but I believe that I have a right
to have my doctors look after my best interests, and for the moment that
consists of living as long and as well as possible.
It is of course possible that my survival of 36 months is a fluke and has
nothing to do with my off-trial treatments. However I hear that EPP is
losing favor, how would I be now if, like a frightened rabbit, I had agreed
to be part of that trial and had been in the surgical arm?
I would not have been skiing in Switzerland last week or be able to cycle
90 km on dirt roads in Cambodia as I did at Christmas.
Evidence is crucial to medicine. However we need to be wary of using it
as a drunk uses a lamppost, more for support than illumination, and I
do not expect or wish to be sacrificed on the altar of evidence-based medicine.