Ailing Dad’s Motivation May Be Son’s Salvation

Floyd Nichols was 19 when his large intestine was surgically removed, an effort to stop a genetic disease that causes deadly colon cancer.

It worked at first, but 16 years later, the disease was threatening his life again. Doctors had little more to offer.

Worse to Nichols, one of his children inherited the disease, leaving him destined to either undergo his dad’s radical intestine operation or get early colon cancer unless doctors found a solution.

Nichols, a Denver businessman unaccustomed to hearing there is no solution, took matters into his own hands. Without any science training, he searched databases until he stumbled onto a potential drug--and recruited doctors in a quest to make the treatment reality in time to protect his son.

Last week, Nichols’ tiny company asked the Food and Drug Administration for permission to sell the drug Aptosyn. Nichols didn’t live to see it, but his 11-year-old son seems to be helped by experimental use of Aptosyn--and his family hopes it will prove Nichols’ legacy for sufferers of the rare familial adenomatous polyposis.

“It’s very sad for me to think that Floyd isn’t here now to see the incredible progress that’s being made,” said his wife, Lynn.

Familial adenomatous polyposis, or FAP, is an insidious inherited disease that causes hundreds of polyps to carpet the large intestine and rectum as early as adolescence. Left untreated, those polyps almost always turn into colon cancer by age 40.

Because many people don’t know they have FAP until it turns cancerous, it’s hard to say how many are affected, but estimates range up to 25,000 Americans.

Current treatment: Remove the large intestine, and sometimes the rectum, so polyps have no place to grow. If the rectum is left, patients need frequent checkups to remove precancerous polyps.

Often the surgery eliminates cancer risk. But it’s incredibly difficult--”horrendous” was Nichols’ word--particularly when patients frequently are in their teens.

Nichols was unusually unlucky, because polyps poised to become cancerous grew back in part of his small intestine when he was 35.

He hunted for last-ditch treatments and discovered that 11 FAP patients in Louisiana had a surprising side effect from the arthritis drug sulindac: It shrank their polyps.

Nichols started taking sulindac in 1989, and his polyps “went right away,” recalled Dr. Rifat Pamukcu, who treated Nichols at the University of Chicago.

But sulindac has another side effect--it’s hard on the stomach, frequently causing ulcers. Pharmaceutical companies told Nichols they weren’t exploring what made sulindac help FAP or creating a stomach-friendly version, so he persuaded his doctor, Pamukcu, to establish their own drug company.

It took 10 grueling years. Nichols furiously raised money to keep the scientists afloat, and Pamukcu recalls the frustration when a failed experiment cost an entire year of work. Then Nichols died suddenly in 1996 of another aggressive cancer, barely a year after his Cell Pathways Inc. began testing its potential FAP drug, Aptosyn.

Aptosyn is a metabolite of sulindac that Pamukcu discovered induced programmed cell death, one of the body’s natural ways of getting rid of cells poised to turn cancerous. In a study of 73 adults with FAP who retained a rectum, Aptosyn caused a 55% reduction in rectal polyps, an effect Pamukcu hopes will protect those people from cancer.

Last year, Nichols’ 11-year-old son became the first child enrolled in an ongoing pediatric study to see if Aptosyn could postpone, if not prevent, intestinal surgery. A checkup shows his intestinal polyps have shrunk, said Mrs. Nichols, who asked that the boy not be named.

The FDA should decide by February whether Philadelphia-based Cell Pathways studied enough people to prove Aptosyn really works. Meanwhile, Aptosyn is being tested on common colon cancer--which strikes more than 120,000 Americans a year who don’t have FAP--and some other tumors.

It’s a promising time. Scientists now know inflammation-fighting drugs can attack colon polyps in a manner different than Aptosyn does. G.D. Searle is seeking FDA approval for its arthritis drug Celebrex to treat FAP, and Merck & Co. is studying competitor Vioxx against FAP too.

Whatever happens with Aptosyn, “this has come a long way” thanks to a dad, Pamukcu said. “This was a motivated man.”