AUSTRALIAN ONCOLOGISTS CRITICIZE CHEMOTHERAPY

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AUSTRALIAN ONCOLOGISTS CRITICIZE CHEMOTHERAPY

_http://www.curenaturalicancro.com/oncologists-criticize-chemotherapy.html_

(http://www.curenaturalicancro.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.)

Table 1

Results for Australian patients

 

_larger image_ (http://www.cancerdecisions.com/images/Table1.jpg)

_http://www.cancerdecisions.com/images/Table1.jpg_

(http://www.cancerdecisions.com/images/Table1.jpg)

source: _http://www.cancerdecisions.com_ (http://www.cancerdecisions.com)

Table 2

Results for US patients

 

_larger image_ (http://www.cancerdecisions.com/images/Table2.jpg)

_http://www.cancerdecisions.com/images/Table2.jpg_

(http://www.cancerdecisions.com/images/Table2.jpg)

source: _http://www.cancerdecisions.com_ (http://www.cancerdecisions.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

commensurately small.

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

damage.

" 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

case.

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

malignancies. "

 

Splitting Hairs

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

in 2006.

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

therapy.

 

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.