“In reality, only 2 major reasons exist for
administering chemotherapy to most patients with metastatic cancer: to help
them live longer and/or to help them live better.”
So begins “Chemotherapy
Near the End of Life: First—and Third and Fourth (Line)—Do No Harm”[1],
an editorial by Charles D. Blanke and Erik K. Fromme in JAMA Oncology commenting on an important new study in the same issue
by Prigerson and colleagues, Chemotherapy
Use, Performance Status, and Quality of Life at the End of Life”.[2] The study, a fairly large randomized controlled
trial, discovered that giving last-ditch chemotherapy for “solid tumors” in
patients estimated to have less than 6 months to live did neither. Not only was
survival time not increased (although the editorialists note that this study
was not designed to look at survival), but quality of life (QOL) was not
improved. Indeed, and incredibly important, the group that had the best quality
of life before receiving this final round of chemotherapy had the greatest drop
in QOL, ending up pretty much as bad as the rest of the group. Blanke and
Fromme observe that that this may be because they had “further to fall”. This
is likely true, but surely the goal is not to give “treatment” that facilitates
that fall.
So why do we do it? Were “we”,
doctors especially, ignorant of this? Certainly the strength of the results –
especially the fact that those whose pre-treatment QOL was the best were those
who were most harmed – was a surprise in that it had never been published
before, but that “palliative” chemotherapy at the end of life, intended
entirely to improve QOL, often does the opposite – is something that every
doctor who cares for patients with cancer, including but not limited to
oncologists, has seen. Many of us, including many palliative care specialists,
usually recommend against such treatment to patients and their families, often
to have our voices drowned out by the encouragement from others (particularly some
oncologists).
The
truth is that the answer, as with so many things involving people, is complex.
People do not usually want to die, and frequently grasp at any straw offered to
them. Even when they themselves are not sure that they wish to go on, even when
their disease makes them unable to make a decision, their family members often take
on the role of demanding more treatment. This rarely if ever comes from a
desire to cause more suffering for a loved one, but rather hoping that a
miracle will occur. When this is encouraged by the physician who offers some
sort of hope it is more likely to happen. The distinction between the outcomes
of palliation and longer life is not always clear to patients or their families,
and indeed “improvement” and “longer life” may mean
different things to the doctor saying it (tumor gets smaller, life expectancy
extended by weeks) and those hearing it.
The
results of this study showing the decrease in QOL for those who were “best off”
prior to treatment should be sobering and decrease the use of end-of-life
chemotherapy, but there continue to be critics of the work. Some oncologists,
typified by the one quoted by Pam Belluck in the New York Times article on the study (“Benefit
of End-Stage Chemotherapy Is Questioned”, July 23, 2015) who “noted that patients
were seen between 2002 and 2008, before some newer chemotherapy drugs with
fewer side effects or the ability to directly target certain tumors or
cancer-causing mutations,” still hold out hope. He may be right, but, of course, all
studies are done in the past, and the “things are better now than then” refrain
is almost always the one we hear from people unhappy with the results; in all
probability, things, for end-of-life cancer patients, are not really better
now.
The
one clearly unacceptable reason for doing such therapy is the financial benefit to the manufacturers of these chemotherapeutic agents, but also to
a lesser degree the providers – mainly the hospitals but also sometimes the
doctors – who administer them. This is a major consideration, not generally
addressed in the articles about this study. “Costs aside,” Blanke and Fromme
write, “we feel the last 6 months of life are not best spent in an oncology
treatment unit or at home suffering the toxic effects of largely ineffectual
therapies for the majority of patients.” The costs that they are holding aside are the costs
of the drugs, the implication is that it is the cost to the patient (or their insurer), a negative
to be weighed against the potential benefit (or not) of the therapy. In this
sense, it is one item on the scale. But the cost to the patient or insurer is
the source of enormous profits to the pharmaceutical companies that make these
incredibly expensive drugs, and they are heavily marketed to physicians by those
multi-billion-dollar corporations. Their marketing campaigns push the
slightest, least-convincingly-demonstrated-by-research potential benefits, and almost
never talk (audibly) about the possible, probable, likely negative effects of
treatment.
While these companies are the greatest financial beneficiaries, so are the hospitals and cancer centers that administer them. The reason that there are so many cancer centers is only in part because cancer is a bad disease; it is largely because it is a very profitable disease to treat because the markup paid by insurers (led by Medicare) for administering chemotherapy is very high. Doctors (particularly oncologists) benefit most directly when they are owners of such cancer centers, but to a lesser degree when they receive high salaries from their employer that are made possible by the huge profits on cancer treatment.
While these companies are the greatest financial beneficiaries, so are the hospitals and cancer centers that administer them. The reason that there are so many cancer centers is only in part because cancer is a bad disease; it is largely because it is a very profitable disease to treat because the markup paid by insurers (led by Medicare) for administering chemotherapy is very high. Doctors (particularly oncologists) benefit most directly when they are owners of such cancer centers, but to a lesser degree when they receive high salaries from their employer that are made possible by the huge profits on cancer treatment.
It
is an ugly thought that your receiving cancer drugs may be in large part
because the manufacturers stand to make a lot of money from it, but there it
is. And it is not just cancer treatment; a recent article in the Business
section of the NY Times from July 24,
2015 by Andrew Pollack, “New
Drug Sharply Lowers Cholesterol, but It’s Costly”, describes the introduction of a new “recombinant
DNA” drug called alirocumab (Praluent) that dramatically lowers cholesterol
levels, but will cost $14,600 a year! This may be a wonder drug for the
relatively small number of people who have familial hypercholesterolemia, but
the indications will unquestionably be pushed by physicians with encouragement from
the manufacturer. Every time there is the least evidence that a drug, initially
intended for the most severely affected patient, can be used for a larger group,
there is more potential for enormous profit. The evidence that just lowering cholesterol as
much as can be done is linearly linked to reducing heart attack and stroke is
limited. “’This is treating a lab value,’ said Dr. Rita Redberg, a cardiologist
at the University of California, San Francisco, referring to lowering
cholesterol for its own sake. ‘I don’t think we should rush into it.’”
“’We
came to a price that is reflective of value, not what the market will bear,’
said Elias Zerhouni, head of research and development at Sanofi [one of the two companies that make
alirocumab], who said his own brother had suffered three heart attacks and
needed new options to control cholesterol.” I am sorry about his brother, but
if you believe that, I’ve got a bridge to sell you. It is absolutely about the
price that the market will bear. The sad part is that there may be some who are
more willing to believe this because Dr. Zerhouni used to be the head of the
National Institutes of Health (NIH), a higher-profile but undoubtedly less
well-paid position. Revolving door, anyone?
Alirocumab
is likely to be beneficial to some patients but will undoubtedly be used in
many more and is unconscionably priced. It’s fine for a company to make profit
on its drugs, but predatory pricing and rapacious profit is not. Most
disturbing is the thought that people who do not need and will not benefit from
a drug, and may even be harmed by it, may receive it mainly so these companies
can profit.
The
line I quote from Blanke and Fromme at the start of this piece
refers to chemotherapy for metastatic cancer, but in fact can be applied far
more generally:
In reality, only 2 reasons exist for administering therapy to patients: to help them live longer and/or to help them live better.
Let’s
keep that, and not corporate profit, as our touchstone.
[1] Blanke CD, Fromme EK, “Chemotherapy Near the End of
Life: First—and Third and Fourth (Line)—Do No Harm”, JAMA Oncology, published online 7/23/15, doi: 10.1001/jamaoncol.2015.2379
[2] Prigerson HG, et al., “Chemotherapy Use, Performance
Status, and Quality of Life at the End of Life”, JAMA Oncol. Published online
July 23, 2015. doi:10.1001/jamaoncol.2015.2378
As a person with multiple sclerosis, I have been offered drugs that cost from $1500 to $4000 a month and are expected to be taken for life or until untoward effects make you stop. These drugs help some people, but studies show the long run benefits are questionable for most patients. It's a cause for despair that super-expensive drugs that usually do more harm than good are being pushed on people known to be at the end of life. It's like fracking - intensification of a paradigm known be destructive, just because it is profitable.
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