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THE MOSS REPORTS Newsletter (05/22/05)

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22 May 2005 21:05:07 -0000

" Cancer Decisions " <

THE MOSS REPORTS Newsletter (05/22/05)

 

 

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

Newsletter #185 05/22/05

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THE MOSS REPORTS

 

 

When physicians reporting the results of a major clinical trial

announce a 23 percent improvement in survival for lung cancer patients

taking

a new drug, it would be hard to see this as anything less than a

breakthrough.

 

But examine this claim a little more closely and you will discover that

the 23 percent improvement in survival actually translates into

patients living for 12.5 months, rather than 10.2 months. Furthermore, a

significant proportion – 4.5 percent - of patients receiving the new

wonder

drug can be expected to die as a direct result of the treatment itself,

a mortality rate which, according to one of the lead researchers

involved, is " well within accepted limits. "

 

There seems to be a vast and widening gulf between the way in which

therapeutic advances of this sort are perceived and reported by the

medical profession, and the real-world benefit that patients can

expect to

receive from submitting to such treatments.

 

This week and next, I report on my visit to the annual meeting of the

American Society of Clincal Oncology, a forum in which, as you will see,

announcements of this sort are plentiful. My goal, as always, is to be

an objective observer, and if it seems to me that the Emperor has no

clothes, I see it as my duty to say so. The most important thing I, in my

capacity as a science journalist, can accomplish is to give my readers

the tools they need in order to make up their own minds and come to

their own conclusions.

 

This has also been my hope and my aim in writing The Moss Reports, a

series of detailed summaries of the best available conventional and

alternative treatments for almost 200 different cancer diagnoses.

 

If you would like to order a Moss Report for yourself or someone you

love, you can do so from our website, www.cancerdecisions.com, or by

calling Diane at 1-800-980-1234 (814-238-3367 from outside the US).

 

We look forward to helping you.

 

 

NOTE: Readers who have high-speed Internet connections as well as the

program QuickTime on their computers are encouraged to look at our first

venture into homemade film journalism. I have made a little 5-minute

movie showing some of the highlights of the ASCO meeting. The movie can

be found at:

http://www.cancerdecisions.com/ASCO2005.mov

 

You may also view the movie at a later time from our archive page on

our site by going to:

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

 

If you do not have the QuickTime plug-in on your computer (Mac or PC),

you can download it for free at:

http://www.apple.com/quicktime/download

 

 

REFLECTIONS ON ASCO 2005

 

 

I have just returned from the 41st annual meeting of the American

Society of Clinical Oncology (ASCO). Twenty-five thousand oncologists

converged on Orlando, Florida, to present their latest work and to learn

about the progress that has been made over the past year in treating

various types of cancer. There were nearly 10,000 abstracts presented

at this

meeting, as well as numerous commercial displays in the vast and

towering exhibition hall. Some of these were masterpieces of advertising

design, although not necessarily of hard science.

 

Like the blind men in the fable trying to describe an elephant, every

observer of a meeting this complex comes away with his or her own,

somewhat subjective, impression. In future issues of this newsletter I

shall

comment on particular studies that I consider most promising. But right

now I would like to give you my personal observations on the state of

oncology as revealed by this ASCO meeting.

 

I first attended an ASCO meeting in the 1970s, when the organization

was relatively small and unknown. The first thing that strikes me, as I

look back, is the dramatic shift from a chemotherapy-based model of

cancer treatment to the new paradigm based around molecularly `targeted'

therapies.

 

Such a change should in fact be welcomed by people who are sympathetic

to complementary and alternative medicine (CAM). The great

philosophical debate over the excess toxicity of standard chemotherapy

has been won

by those favoring a " kinder, gentler " approach to cancer treatment.

Indeed, almost every speech and most of the poster sessions featured

targeted drugs of one description or another.

 

At the same time, I find little in the actual practice of targeted

therapy to kindle much enthusiasm. In this, I am at odds with most

leaders

of oncology. For instance, in his 2005 Karnofsky Memorial Lecture (the

highest honor given by ASCO), Charles L. Sawyers, MD, of the University

of California at Los Angeles (UCLA), spoke for many of his colleagues

when he said that the age of molecularly targeted cancer therapy had

unquestionably arrived. As he saw it, the fact that so many presentations

focused on the use of so-called tyrosine kinase inhibitors such as

imatinib (Gleevec), gefitinib (Iressa) and erlotinib (Tarceva) validated

the basic concepts of targeted therapy.

 

Since it has been seven years since the Food and Drug Administration

(FDA) approved Herceptin (trastuzumab), one of the very first targeted

drugs, to treat breast cancer, and four years since it approved Gleevec

for chronic myelogenous leukemia (CML), one could certainly expect to

see some definitive proof of the targeted treatment philosophy. But while

such agents have undoubtedly scored some successes over the

years—Gleevec in particular is a very worthwhile agent—the field as a

whole has

run into many unanticipated obstacles as it tries to tackle the common

tumors of adults.

 

In particular, it has turned out that these agents have more side

effects than was predicted initially by advocates of molecular targeting.

For example, take the surprisingly widespread occurrence of potentially

fatal bleeding episodes with the drug Avastin (bevacizumab). According

to the manufacturer's own website:

 

" Serious, and in some cases fatal, hemoptysis [the coughing of blood

from the lungs, ed.] has occurred in patients with non-small cell lung

cancer treated with chemotherapy and Avastin. In a small study, the

incidence of serious or fatal hemoptysis was 31 percent in patients with

squamous histology and 4 percent in patients with adenocarcinoma

receiving

Avastin as compared to no cases in patients treated with chemotherapy

alone. Patients with recent hemoptysis should not receive Avastin. "

 

In addition, when given as stand-alone treatments, most of these agents

have demonstrated surprisingly poor results in various clinical trials.

As was seen recently with the phase III clinical trials of Iressa, they

sometimes do not actually extend overall survival at all. In April,

2005, the US National Cancer Institute (NCI) decided to discontinue all

further clinical trials with Iressa, once a front-runner in the targeted

therapy movement. " Iressa Clinical Trials Squashed Like a Nasty

Cigarette Butt, " is how one former pharmaceutical developer (Stacey

Lloyd)

graphically summed up NCI's action.

 

 

Plenary Session Disappointments

 

 

At the ASCO plenary session held on Saturday afternoon (May 14, 2005),

there was a discussion of three different combinations of chemotherapy

with targeted drugs, in this case antiangiogenic agents. Such agents

are designed to stop the formation of new blood vessels that can promote

the growth of tumors. This session illustrated the complex obstacles

that researchers in this field have encountered. Two of the speakers

reported that the targeted drug bevacizumab (Avastin) provided what they

called a significant survival advantage in patients with metastatic

colorectal cancer and advanced non-small cell lung cancer, respectively.

However, a third study, using the up-and-coming antiangiogenic drug

PTK/ZK, failed to show that this drug significantly improved

progression-free

survival when given in combination with chemotherapy as a first-line

treatment for advanced colorectal cancer.

 

At first sight, you might think that two positive trials out of three

is not bad. However, what the survival numbers actually show is

something quite different. Thus, when Avastin was given alone to

patients with

metastatic colorectal cancer, their median overall survival was just

10.2 months. A standard chemo regimen of 5-FU, leucovorin and

oxaliplatin, called FOLFOX 4, yielded a very similar 10.8 months. Only

when the

two treatments were administered together did survival rise to 12.9

months. Thus there was a gain of two months through the use of this

intensive - and expensive - regimen. How much of this increased

survival time

was spent by patients feeling sick because of toxicity remains to be

discovered.

 

NOTE: The median is the middle number in a set of ordered data. Thus,

the median of the numbers 1,1,1,2,4,6,6 is 2 since 2 is the middle

number when all of the numbers are placed in order. In statistics, the

median is considered a more reliable measure than the mean, which is more

commonly what is meant by the word " average. "

 

Another figure that oncologists frequently look at is median

progression-free survival (PFS). This refers to the time that elapses

between

administration of the treatment and the time that progression of the

disease is detected in a living patient. Here the figures were even less

encouraging. With Avastin alone, this period of remission was just 2.7

months. With FOLFOX 4 alone it was 4.8 months. When the two were given

together it was 7.2 months. At that point, the cancer was detected to be

once again on the march. So, again, we're talking about a gain of a few

months.

 

In the second reported trial, the standard regimen FOLFOX4 was given

with PTK/ZK, a new orally administered, targeted antiangiogenic agent.

The effects of this combination were then compared to FOLFOX 4 given with

a placebo pill. No figures on median overall survival will be available

until 2006. But the combination that included PTK/ZK yielded an average

(median) progression-free survival of 7.7 months. This was nearly

identical to the 7.6 months experienced by the FOLFOX 4 group. It seems

therefore that in this group of patients the new drug had no effect on

the

progression of their cancer.

 

In a third trial, a standard regimen of two drugs, paclitaxel and

carboplatin (PC), was compared to PC + bevacizumab (Avastin) in the

treatment of metastatic non-small cell lung cancer. The median overall

survival

here was 10.2 months for PC alone vs. 12.5 months when Avastin was

added. The median progression free survival was 4.5 months for PC

alone vs.

6.4 months for the combination. These studies support the idea that

Avastin (at least in clinical trials) adds around two months to disease

free and to overall survival when it is added to standard chemotherapy

for some advanced solid tumors of adults.

 

TO BE CONCLUDED, WITH REFERENCES, NEXT WEEK.

 

 

--Ralph W. Moss, PhD

 

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IMPORTANT DISCLAIMERS

 

The news and other items in this newsletter are intended for

informational purposes only. Nothing in this newsletter is intended to

be a

substitute for professional medical advice.

 

Copyright © The Internet Society (2004). This document is subject to

the rights, licenses and restrictions contained in BCP 78, and except

as set forth therein, the authors retain all their rights.

 

This document and the information contained herein are provided on an

" AS IS " basis and THE CONTRIBUTOR, THE ORGANIZATION HE/SHE REPRESENTS OR

IS SPONSORED BY (IF ANY), THE INTERNET SOCIETY AND THE INTERNET

ENGINEERING TASK FORCE DISCLAIM ALL WARRANTIES, EXPRESS OR IMPLIED,

INCLUDING

BUT NOT LIMITED TO ANY WARRANTY THAT THE USE OF THE INFORMATION HEREIN

WILL NOT INFRINGE ANY RIGHTS OR ANY IMPLIED WARRANTIES OF

MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE.

 

This document may not be modified, and derivative works of it may not

be created.

 

--------------

 

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