Chemotherapy criticised by Australian oncologists
Posted by Jonathan Chamberlain on August 29, 2008
posted on Cancercured yahoo health group:
AUSTRALIAN ONCOLOGISTS CRITICIZE CHEMOTHERAPY
_http://www.curenatu ralicancro. com/oncologists- criticize- chemotherapy. html_
(http://www.curenatu ralicancro. com/oncologists- criticize- chemotherapy. html)
An important paper has been published in the journal Clinical Oncology. This
meta-analysis, entitled “The Contribution of Cytotoxic Chemotherapy to
5-year Survival in Adult Malignancies” set out to accurately quantify and assess
the actual benefit conferred by chemotherapy in the treatment of adults with
the commonest types of cancer. Although the paper has attracted some attention
in Australia, the native country of the paper’s authors, it has been greeted
with complete silence on this side of the world.
All three of the paper’s authors are oncologists. Lead author Associate
Professor Graeme Morgan is a radiation oncologist at Royal North Shore Hospital
in Sydney; Professor Robyn Ward is a medical oncologist at University of New
South Wales/St. Vincent’s Hospital. The third author, Dr. Michael Barton, is a
radiation oncologist and a member of the Collaboration for Cancer Outcomes
Research and Evaluation, Liverpool Health Service, Sydney. Prof. Ward is also a
member of the Therapeutic Goods Authority of the Australian Federal
Department of Health and Aging, the official body that advises the Australian
government on the suitability and efficacy of drugs to be listed on the national
Pharmaceutical Benefits Schedule (PBS) – roughly the equivalent of the US Food
and Drug Administration.
Their meticulous study was based on an analysis of the results of all the
randomized, controlled clinical trials (RCTs) performed in Australia and the US
that reported a statistically significant increase in 5-year survival due to
the use of chemotherapy in adult malignancies. Survival data were drawn from
the Australian cancer registries and the US National Cancer Institute’s
Surveillance Epidemiology and End Results (SEER) registry spanning the period
January 1990 until January 2004.
Wherever data were uncertain, the authors deliberately erred on the side of
over-estimating the benefit of chemotherapy. Even so, the study concluded
that overall, chemotherapy contributes just over 2 percent to improved survival
in cancer patients.
Yet despite the mounting evidence of chemotherapy’ s lack of effectiveness in
prolonging survival, oncologists continue to present chemotherapy as a
rational and promising approach to cancer treatment.
“Some practitioners still remain optimistic that cytotoxic chemotherapy will
significantly improve cancer survival,” the authors wrote in their
introduction. “However, despite the use of new and expensive single and combination
drugs to improve response rates…there has been little impact from the use of
newer regimens” (Morgan 2005).
The Australian authors continued: “…in lung cancer, the median survival
has increased by only 2 months [during the past 20 years, ed.] and an overall
survival benefit of less than 5 percent has been achieved in the adjuvant
treatment of breast, colon and head and neck cancers.”
The results of the study are summarized in two tables, reproduced below.
Table 1 shows the results for Australian patients; Table 2 shows the results for
US patients. The authors point out that the similarity of the figures for
Australia and the US make it very likely that the recorded benefit of 2.5
percent or less would be mirrored in other developed countries also.
(NB: We apologize for the poor image quality of these tables. The blanks in
the columns represent zero, i.e. no direct benefit can be attributed to
chemotherapy; no patients in that category achieved an increased 5-year survival
due to chemotherapy. )
Results for Australian patients
_larger image_ (http://www.cancerde cisions.com/ images/Table1. jpg)
_http://www.cancerde cisions.com/ images/Table1. jpg_
(http://www.cancerde cisions.com/ images/Table1. jpg)
source: _http://www.cancerde cisions.com_ (http://www.cancerde cisions.com)
Results for US patients
_larger image_ (http://www.cancerde cisions.com/ images/Table2. jpg)
_http://www.cancerde cisions.com/ images/Table2. jpg_
(http://www.cancerde cisions.com/ images/Table2. jpg)
source: _http://www.cancerde cisions.com_ (http://www.cancerde cisions.com)
Basically, the authors found that the contribution of chemotherapy to 5-year
survival in adults was 2.3 percent in Australia, and 2.1 percent in the USA.
They emphasize that, for reasons explained in detail in the study, these
figures “should be regarded as the upper limit of effectiveness” (i.e., they are
an optimistic rather than a pessimistic estimate).
Understanding Relative Risk
How is it possible that patients are routinely offered chemotherapy when the
benefits to be gained by such an approach are generally so small? In their
discussion, the authors address this crucial question and cite the tendency on
the part of the medical profession to present the benefits of chemotherapy in
statistical terms that, while technically accurate, are seldom clearly
understood by patients.
For example, oncologists frequently express the benefits of chemotherapy in
terms of what is called “relative risk” rather than giving a straight
assessment of the likely impact on overall survival. Relative risk is a statistical
means of expressing the benefit of receiving a medical intervention in a way
that, while technically accurate, has the effect of making the intervention
look considerably more beneficial than it truly is. If receiving a treatment
causes a patient’s risk to drop from 4 percent to 2 percent, this can be
expressed as a decrease in relative risk of 50 percent. On face value that sounds
good. But another, equally valid way of expressing this is to say that it
offers a 2 percent reduction in absolute risk, which is less likely to convince
patients to take the treatment.
It is not only patients who are misled by the overuse of relative risk in
reporting the results of medical interventions. Several studies have shown that
physicians are also frequently beguiled by this kind of statistical sleight
of hand. According to one such study, published in the British Medical
Journal, physicians’ views of the effectiveness of drugs, and their decision to
prescribe such drugs, was significantly influenced by the way in which clinical
trials of these drugs were reported. When results were expressed as a relative
risk reduction, physicians believed the drugs were more effective and were
strongly more inclined to prescribe than they were when the identical results
were expressed as an absolute risk reduction (Bucher 1994).
Another study, published in the Journal of Clinical Oncology, demonstrated
that the way in which survival benefits are presented specifically influenced
the decision of medical professionals to recommend chemotherapy. Since 80
percent of patients chose what their oncologist recommends, the way in which the
oncologist perceives and conveys the benefits of treatment is of vital
importance. This study showed that when physicians are given relative risk
reduction figures for a chemotherapy regimen, they are more likely to recommend it
to their patients than when they are given the mathematically identical
information expressed as an absolute risk reduction (Chao 2003).
The way that medical information is reported in the professional literature
therefore clearly has an important influence on the treatment recommendations
oncologists make. A drug that can be said, for example, to reduce cancer
recurrence by 50 percent, is likely to get the attention and respect of
oncologists and patients alike, even though the absolute risk may only be a small one
– perhaps only 2 or 3 percent – and the reduction in absolute risk
To their credit, the Australian authors of the study on the effectiveness of
chemotherapy address the issue of relative versus absolute risk. They suggest
that the apparent gulf between the public perception of chemotherapy’ s
effectiveness and its actual mediocre track record can largely be attributed to
the tendency of both the media and the medical profession to express efficacy
in terms of relative rather than absolute risk .
“The minimal impact on survival in the more common cancers conflicts with the
perceptions of many patients who feel they are receiving a treatment that
will significantly enhance their chances of cure,” the authors wrote. “In part
this represents the presentation of data as a reduction in risk rather than
as an absolute survival benefit and by exaggerating the response rates by
including ‘stable disease.'”
As an example of how chemotherapy is oversold, they cite the treatment of
breast cancer. In 1998 in Australia, out of the total of 10,661 women who were
newly diagnosed with breast cancer, 4,638 women were considered eligible for
chemotherapy. Of these 4,638 women, only 164 (3.5 percent) actually gained
some survival benefit from chemotherapy. As the authors point out, the use of
newer chemotherapy regimens including the taxanes and anthracyclines for breast
cancer may raise survival by an estimated additional one percent – but this
is achieved at the expense of an increased risk of cardiac toxicity and nerve
“There is also no convincing evidence,” they write, “that using regimens with
newer and more expensive drugs is any more beneficial than the regimens used
in the 1970s.” They add that two systematic reviews of the evidence been not
been able to demonstrate any survival benefit for chemotherapy in recurrent
or metastatic breast cancer.
Another factor clouding the issue is the growing trend for clinical trials to
use what are called ‘surrogate end points,’ as a yardstick by which to
measure a chemotherapy regimen’s effectiveness. This is instead of using the only
real measures that matters to patients – prolongation of life as measured by
overall survival and improved quality of life. Surrogate end points such as
‘progression- free survival,’ ‘disease-free survival’ or ‘recurrence- free
survival’ may only reflect temporary lulls in the progression of the disease.
Such temporary stabilization of disease, if it occurs at all, seldom lasts for
more than a few months at best. The cancer typically returns, sometimes with
renewed vigor, and survival is not generally extended by such interventions.
However, trials reported in terms of surrogate end points can create the
illusion that the lives of desperately ill patients are being significantly
extended or made more bearable by chemotherapy, when in reality this is not the
In summary, the authors state:
“The introduction of cytotoxic chemotherapy for solid tumors and the
establishment of the sub-specialty of medical oncology have been accepted as an
advance in cancer management. However, despite the early claims of chemotherapy
as the panacea for curing all cancers, the impact of cytotoxic chemotherapy is
limited to small subgroups of patients and mostly occurs in the less common
In view of the highly controversial nature of the study’s findings, one might
have expected it to receive enormous international attention. Instead, media
reaction has been largely limited to the authors’ native land of Australia;
the study received almost no coverage whatsoever in the US. In fact, although
the paper appeared in December 2004, there was limited coverage even Down
Under. The authors were interviewed for the Australian Broadcasting Corporation
(ABC) program The Health Report in April 2005. But their landmark paper did
not come to most doctors’ attention until a widely distributed medical
practice periodical, the Australian Prescriber, ran an editorial on the study early
On ABC’s The Health Report, Prof. Morgan, the paper’s principal author,
reiterated the study’s conclusions that chemotherapy had been oversold, and
pointed to the fact that relative risk reduction is being used as the yardstick of
efficacy, with its deceptively large percentage differences.
For balance, the show host, Norman Swan, interviewed Prof. Michael Boyer,
chief of medical oncology at Australia’s Royal Prince Albert Hospital, Sydney.
Unable to deny the validity of the study’s essential findings, Prof. Boyer
instead attempted to nitpick the authors’ methodology. He suggested that the
figure for chemotherapy’ s efficacy was actually somewhat higher than the study
had concluded. Yet even so, when pushed, the most favorable figure he could
come up with was that chemotherapy might actually be effective in 5 or 6
percent of cases (instead of around 2 percent).
Interviewed by Australian Prescriber, Prof. Boyer similarly commented: “If
you start…saying how much does chemotherapy add in the people that you might
actually use it [in], the numbers start creeping up…to 5 percent or 6
percent” (Segelov 2006).
In my opinion, this sort of hair-splitting damns chemotherapy with faint
praise. It actually confirms the central message of the three critics’ study. If
the best defense of chemotherapy that orthodox oncology can come up with is
that it may actually be effective for 5 or 6 percent of cancer patients,
rather than merely 2 percent, then surely it is high time for a radical
reassessment of the widespread use of this toxic modality in cancer treatment. Either
figure – 2 percent or 6 percent – will come as a shock to most patients
offered this type of treatment, and ought to generate serious doubt in the minds of
oncologists as to the ethics of offering chemotherapy without explicitly
warning patients of its unlikely prospects for success.
It was also astonishing that the orthodox Prof. Boyer complained that one of
the major shortcomings of the study was that it insisted on measuring
absolute instead of relative benefits. Asked by the interviewer whether there
weren’t violations of informed consent implicit in the way that benefits of
treatment were usually presented, Prof. Boyer defended the use of the more
impressive-sounding relative risk reduction:
“One of the problems of this [Morgan, ed.] paper is it uses absolute benefits
rather than relative benefits,” he protested: “…the relative benefit is
about a one third reduction in your risk of death.”
This, of course, is precisely the reverse of the argument made by the study’s
authors, who clearly demonstrated the misleading nature of relative risk
reduction as a means of describing the efficacy of chemotherapy.
Other Critics Emerge
Prof. Morgan and his Australian colleagues are not alone in criticizing the
pervasive use of relative risk as a means of inflating treatment efficacy.
There have been others in recent years who have also voiced concern about this
trend. For example, in a letter to the editor of the medical practice journal
American Family Physician, James McCormack, PharmD, a member of the faculty
of Pharmaceutical Sciences, University of British Columbia, made this same
point about relative vs. absolute risk with great clarity.
Dr. McCormack took as an example the prescription of the bisphosphonate drugs
in the treatment and prevention of osteoporosis. ..but identical issues apply
to the use of anticancer drugs. The journal in question had written that one
of those drugs produced almost “a 50 percent decrease” in the risk of new
fractures. Addressing himself to a hypothetical patient, Dr. McCormack
reinterpreted this statement in terms of absolute risk: “Mrs. Jones, your risk of
developing a…fracture over the next three years is approximately 8 percent.
If you take a drug daily for the next three years, that risk can be reduced
from 8 percent to around 5 percent, or a difference of just over 3 percent.” Of
course that sounds far less impressive than saying that taking the drug will
decrease the risk of fracture by almost half, even though technically both
are mathematically accurate ways of expressing the benefit to be gained by the
The Good News and the Bad
News concerning conventional cancer treatments seems to come in two
varieties: good and bad. Good news, meaning that conventional treatments work well,
often generates widespread press coverage and enthusiastic statements from
health officials. On the other hand, bad news, such as the fact that
conventional treatments have generally been oversold, usually comes and goes unseen,
attracting no media attention whatsoever.
An example of the first kind is the recent announcement that for the first
time in 70 years, the absolute number of US cancer deaths had fallen. Andrew C.
von Eschenbach, MD, director of the US National Cancer Institute (NCI),
called this “momentous news.” Similarly, Dr. Michael Thun, head of
epidemiological research for the American Cancer Society, said it was “a notable
milestone.” How big was the celebrated decline? As we reported in a recent newsletter,
deaths actually fell by a total of 370, from 557,272 in 2003 to 556,902 in
2004. Expressed as a percentage of the total, it represents a drop of seven
hundredths of one percent (0.066 percent).
Contrast the wildly enthusiastic coverage given to this tiny improvement in
the annual cancer death rate with the almost total media blackout (at least in
North America) on this critical paper from Australia. Yet nothing can
obscure the fact that chemotherapy, for most indications, has far less
effectiveness than the public is being led to believe. Dr. Morgan and his colleagues
deserve every reader’s gratitude for having pointed this out to their colleagues
around the world.