Drugs shrink basal cell cancer in 1st human guinea pig
by Kate Nolan - May. 21, 2008 12:06 PM
The Arizona Republic
SCOTTSDALE - Jerry Coffman lives from scan to scan.
He used to live on his Lazy-Boy, wiped out most the time and anticipating hospice care.
Now, Coffman works out at the gym twice a week and stops at the Virginia G. Piper Cancer Center every eight weeks for the computed tomography imaging scans that search his body for cancer.
He muses on the wonder of his survival, the result of CDC-0449, an experimental drug for which he was the first human guinea pig.
Coffman, 69, has basal cell carcinoma, the most common form of skin cancer.
Typically caused by sun exposure, basal cell affects about 1 million Americans annually. Most are treated successfully with minor surgery. But for a few patients, like Coffman, the cancer cells run amok, targeting other organs until the patient dies.
"It got into my lungs, spine and hips, and was beginning to affect my life," said Coffman, a retired Phoenix city worker, who was treated on and off since 1991.
He endured lung surgery, three rounds of radiation therapy and an unsuccessful experimental treatment before getting the one that worked.
The novel CDC-0449 molecule continues to undergo Phase I testing by TGen Clinical Research Services at Scottsdale Healthcare in Scottsdale. Thanks to Coffman and eight other patients who took the oral medication, researchers now know CDC-0449 shrinks tumors for patients with advanced basal cell carcinoma.
According to Coffman, he was lucky, the end guy in a chain of coincidences:
• After five years, the drug company happened to be ready to test the drug.
• The company picked Scottsdale Healthcare as the first clinical site.
• Coffman happened to be referred there.
Hanging on a few more months
"Dr. Von Hoff told me they had something coming on line, if I could hang on six months," Coffman said.
Dr. Daniel Von Hoff, world renowned for his discoveries in pancreatic cancer, was looking into basal cell carcinoma in his dual roles as chief physician for both TGen (the Translational Genomics Research Institute) and the Scottsdale Clinical Research Institute at Scottsdale Healthcare, a Northeast Valley hospital network.
"This number 1 patient with advanced cancer waited for this, and a year later he bakes us a beautiful cake," said Von Hoff, who reported on Coffman's success in April at a national medical conference.
Phase 1 trials typically test for safety and dosage, but the effectiveness was so apparent that Von Hoff and his colleagues, whose work was sponsored by Genentech, had far more to report.
The results show that in eight of the nine patients tested, tumors shrank after treatment with CDC-0449.
First patient still going strong
Coffman has long exceeded the 450 days of survival cited in the study. And, like the other patients, has experienced almost no side effects beyond minimal hair loss.
What's happening on the molecular level is a war between dueling genes that was first noticed by shepards in Idaho in the 1950s.
"They had some lambs born with a Cyclops, a single eye," Von Hoff said. Someone figured out a chemical in a plant called the corn lily, eaten by mother sheep, stopped development of the lambs' second eye by turning certain genes off and on.
The chemical was dubbed cyclopamine, and the "signaling pathway" was later found in humans and dubbed the hedgehog pathway, because its molecule looks like Sonic Hedgehog, the mascot of a Sega videogame.
Cyclopamine, it was found, could block abnormal cell growth in a number of human cancers, including basal cell carcinoma.
Curis Inc., a Massachusetts drug company is partnering with Genentech to develop synthetic forms of cyclopamine to treat basal cell and other tumors.
"I had patients referred to me with basal cell that had gone deeply into the brain - one bad-ass basal cell. There was little to do for it. I asked Genentech if I could be an investigator and they agreed," said Von Hoff.
"I had a patient here who had progressive disease that metastasized to the liver, bone and lung. He became the first man in the world to get the drug," Von Hoff said of Coffman, whose tumors shrank in all areas.
How other patients progressed
In a second patient, a scabby open sore on the ear disappeared.
A third patient's ear was being eaten away, but grew back after treatment.
A fourth patient got his lungs back.
And so on.
Treatment was unsuccessful for one of the nine enrolled in the study, a man treated at Johns Hopkins' cancer center, who failed to survive.
The significance of the story, according to Von Hoff, is that successful treatments may exist for patients with advanced cancer who are told there is no standard therapy.
"These are fairly dramatic results, and we are looking into other tumor types," said Von Hoff, observing that only two percent of patients who qualify for experimental therapies get them.
"The tragedy is that we have 20 or more other agents that may help people who have not progressed on other therapies," said Von Hoff.
Twelve slots are open in the "hedgehog pathway" study, which is open to patients with basal cell, pancreatic, colon and prostate cancer.
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