[MOL] Colon Cancer research [02421] Medicine On Line

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[MOL] Colon Cancer research

Report: Drug Combination May Prevent Colon Cancer

 By Maggie Fox

 WASHINGTON (Aug. 29) - A combination of old and new drugs may be
 a safe way to prevent colon cancer in some people, researchers said on 

 The old drug, an analgesic known as sulindac, combined with Wyeth-Ayerst's
 experimental drug EKB-569, prevented the formation of potentially cancerous
 polyps in half of the mice tested by researchers at Johns Hopkins University
 in Baltimore and Wyeth-Ayerst Research.

 ''Our results indicate a promising avenue for (using drugs to prevent)
 colorectal cancer in humans in the future,'' the researchers wrote in their
 report, published in the journal Nature Medicine.

 Aspirin and similar drugs have been shown to possibly prevent colon
cancer, which is the third-leading cancer killer in the United States and some
other industrialized countries.

 But such drugs can have deadly side-effects. An estimated 16,000 Americans
 die every year from gastrointestinal bleeding and other side-effects caused
 by aspirin and related non-steroidal anti-inflammatory drugs (NSAIDS).

 Wyeth researchers, working with colon cancer expert Dr. Bert Vogelstein and
 colleagues at Johns Hopkins, looked for a way to reduce this danger.

 They fine-tuned one product, named it EKB-569, and tested it on mice along
 with the NSAID sulindac, which has been used experimentally to prevent
colon cancer but which can have the fatal bleeding side-effects.

 EKI-569 interferes with an enzyme known as epidermal growth factor receptor
 (EGFR) kinase. The EGF family has often been associated with colon cancer
as well as some breast cancers.

 They gave the combination to specially bred mice, who have a genetic defect
 similar to that found in people with familial adenomatous polyposis (FAP),
a  syndrome that can make them susceptible to colon cancer.

 ''EKB-569, when used alone, reduced polyp formation by 87 percent,'' the
 researchers wrote.
 ''The combination of EKB-569 and sulindac provided striking protection
from  tumour development,'' they added -- a 95 percent reduction in
pre-tumourous  polyps.

 ''Forty-seven percent of ... mice treated with the combination therapy had
no tumors at all, whereas 100 percent of mice in the (untreated) control
group developed tumors, with an average of 20 polyps per mouse.''

 The mice suffered no apparent ill side-effects, and when they were killed
and examined, did not seem to have any inflammation of the intestines.

 ''Even the animals that did get tumors only had one or two, compared to
the untreated control mice which developed an average of 20 tumors. So, we
felt very encouraged by these results,'' Vogelstein said in a statement.

 Commenting on the study, Dr. Raymond DuBois of Vanderbilt University in
 Nashville said a new class of drugs, the COX-2 inhibitors, might work even
 better with EKB-569.

 The COX-2 inhibitors were designed to have fewer side-effects than NSAIDs
and some have been associated with a reduction in colon cancer risk.

 ''They are proven to have a better safety profile,'' DuBois said in a
 telephone interview.

 He is currently testing two of them, Merck's Vioxx and Celebrex, made by
 Searle, a division of Pharmacia Corp., with agents made by rival drug

 DuBois said he could not give details of the rival drugs, but said they
 worked in a similar way to EKB-569. ''There might be an even better
 combination that could be effective,'' he said.

 But he cautioned that it is very different to affect cancer in laboratory
 mice and cancer in humans. ''I don't know if this mouse model is going to
be predictive of what happens in humans,'' he said.

 And DuBois pointed out that while doctors assume the polyps become
cancerous, it has not been proven that preventing the growth of polyps will
completely prevent cancer.

 ''The only way we know if something is going to work well in patients is
 actually to do the clinical trial and test it,'' he said.

 Reut18:33 08-29-00
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