Sulindac sulfone, a nonsteroidal anti-inflammatory drug (NSAID)
recently tested in the laboratories of the Arizona Cancer Center,
may prove to be an effective colon cancer preventive agent.
Within the last few years, reports the Arizona center, research
has suggested that NSAIDs may be effective in preventing colorectal
cancer. Sulindac reduces the growth of colon polyps in patients
with familial adenomatous polyposis (FAP). Since most colon cancers
develop from colon polyps, stopping polyp growth may reduce cancer
"Although sulindac prevents polyp growth, many patients experience
side effects, such as upper gastrointestinal (GI) disturbances.
Consequently, only about one third of patients can tolerate the
drug for prolonged treatment periods," explains David S.
Alberts, MD, director of cancer prevention and control. Dr. Alberts
worked on the NSAID research with Klaus Brendel, PhD, professor
of pharmacology, and Lee Hixson, MD, who since has moved from
the University of Arizona.
"Most patients cannot stay on sulindac long enough for it
to be an effective chemopreventive agent because this would require
daily use, perhaps for life," Dr. Alberts said.
"In looking for a better colon cancer preventive drug, we
decided to study derivatives of sulindac, to find the active ingredient
responsible for reducing colon polyps. The object was to find
a better way to deliver the active ingredient and reduce the side
Several research papers suggested that sulindac's side effects
were related to the production of prostaglandins. Sulindac inhibits
production of prostaglandins, and many researchers believe that
stopping prostaglandin production prevents tumor formation, according
to Dr. Alberts.
However, more recent studies conflict with this viewpoint and
show that tumors grow even in the absence of prostaglandin. Dr.
Alberts' group decided to focus their research on sulindac sulfone,
an "inactive" metabolite of sulindac. Previously sulindac
sulfone was not shown to be active as an anti-inflammatory agent,
and it does not inhibit prostaglandin production.
"Preclinical indications suggest that sulindac sulfone may
be as effective as sulindac in reducing colon polyp growth in
patients with familial adenomatous polyposis but without the GI
side effects. This means patients who can't take sulindac may
have a chance to reduce their risk of colon cancer by taking sulindac
sulfone," says Dr. Alberts.
The sulindac sulfone study was supported by a grant from Cell
Pathways, Inc., of Denver, Colorado, which has licensed the drug
from the Technology Transfer Office of the University of Arizona.
Cell Pathways also coordinated the clinical trials. The phase
I trial, which involved 33 people without FAP, didn't identify
any safety problems with the drug, but "we still have a long
way to go in the testing process," says Floyd Nicholls, chief
executive officer of Cell Pathways. The next study, which will
start later this year, will involve patients with FAP.