THE MOSS REPORTS Newsletter (03/12/06)

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13 Mar 2006 00:10:35 -0000

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THE MOSS REPORTS Newsletter (03/12/06)

 

 

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Ralph W. Moss, Ph.D. Weekly CancerDecisions.com

Newsletter #227 03/12/06

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http://www.cancerdecisions.com/031206.html

 

 

AUSTRALIAN ONCOLOGISTS CRITICIZE CHEMOTHERAPY, PART TWO

 

 

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.

 

 

 

Signature

--Ralph W. Moss, Ph.D.

 

References:

 

 

Australian Broadcasting Corporation (ABC) Health Report – Available from:

http://www.abc.net.au/rn/talks/8.30/helthrpt/stories/s1348333.htm

 

Bucher HC, Weinbacher M, Gyr K. Influence of method of reporting study

results on decision of physicians to prescribe drugs to lower

cholesterol concentration. BMJ. 1994;309:761-764.

 

Chao C, Studts JL, Abell T, et al. Adjuvant chemotherapy for breast

cancer: how presentation of recurrence risk influences

decision-making. J Clin Oncol. 2003; 21 (23):4299-4305.

 

Morgan G, Ward R, Barton M. The contribution of cytotoxic chemotherapy

to 5-year survival in adult malignancies. Clin Oncol (R Coll Radiol).

2004;16(8):549-60.

 

Segelov, E. The emperor's new clothes – can chemotherapy survive?

Australian Prescriber. 2006; 29 (1):2-3

 

For copies of my book, Questioning Chemotherapy, click or go to:

http://www.amazon.com/exec/obidos/dt/assoc/tg/aa/xml/assoc/-/188102525X/cancerde\

cisio-20/ref%3Dac%5Fbb6%5F%2C%5Famazon/104-1661683-0762302