A new generation of medications to treat leukemia is wiping out cancer in people who fail to benefit from the blockbuster drug Gleevec, (search) researchers say.
One of the new drugs, known as BMS-354825, obliterated signs of leukemia (search) in nearly nine of 10 people who took it, says Charles Sawyers, MD, a cancer specialist at the University of California, Los Angeles, who is leading tests of the drug.
Sawyers and others spoke about the novel drugs at the annual meeting of the American Society of Hematology this week. The experimental medications are being tested in patients with chronic myeloid leukemia (search) or CML, a blood and bone marrow cancer that strikes about 4,400 Americans and 10,000 people worldwide each year.
When Gleevec came on the market in 2001, it was considered revolutionary — one of the first targeted therapies to seek out and destroy only cancerous cells, leaving surrounding healthy tissue unscathed. Not only do targeted therapies work better, but they avoid many of the side effects, such as nausea and hair loss, associated with traditional chemotherapy.
Overnight, the pill became the standard treatment for CML because it was relatively safe, easy to administer, and worked fast to produce excellent clinical remissions, says Stanley Schrier, MD, active emeritus professor of medicine/hematology at Stanford University School of Medicine in Palo Alto and president of the American Society of Hematology.
But after three years of treatment, about 15 percent of people with CML stop responding to Gleevec – “a devastating experience,” says Kanti Rai, MD, vice president of the American Society of Hematology and a cancer specialist at Albert Einstein School of Medicine in New York.
“After being told that the drug might cure them, the cancer comes back. It’s a letdown of unimaginable proportions.”
That’s where BMS-354825, made by Bristol-Myers Squibb, comes in. “It’s groundbreaking,” Rai tells WebMD.
Understanding Cancer’s Roots
A better understanding of the genetic alterations involved in leukemia led to the development of both Gleevec and the new drugs, Sawyers says.
Gleevec targets a mutation in the protein BCR-ABL, which allows cells to multiply unchecked.
Like a key in a lock, it attaches to the cancerous cells and stops them from growing and spreading, he explains.
But some people develop a mutation at the site where Gleevec attaches. “Think of it as a rusty lock,” Sawyers says. “The key doesn’t fit so tightly any more.”
BMS-354825 attacks a different protein called SRC that binds in a different — and broader — way. “It’s clearly working,” Sawyers tells WebMD. “We’re extremely excited.”
In 26 patients with chronic myeloid leukemia who developed resistance to Gleevec, 19 (73%) had a complete response to BMS-354825, meaning their bodies stopped producing the leukemia cells, he says.
Seven people had a partial response to BMS-354825, one of whom developed a leukemia that was resistant to both Gleevec and BMS-354825.
So far the drug appears to be extremely well tolerated, Sawyers says.
A Second Second-Generation Leukemia Pill
Also at the meeting, Francis Giles, MD, a cancer specialist at the University of Texas M.D. Anderson Cancer Center in Houston, reported on another second generation leukemia pill.
Known as AMN107, the drug produced dramatic response rates in about half of 76 people with advanced CML, Giles says. Noting that patients were given an extremely low dose, he says higher doses might work even better.
AMN107 is up to 30 times more potent than Gleevec because it was designed to more efficiently bind to the enzyme that’s faulty in CML, he says.
"Gleevec changed everything in CML,” Giles says. “But a drug that can cope with resistance to Gleevec might do even better across the board.”
Rai agrees. Studies suggest that the second-generation pills might work against other cancers, including other types of leukemia and some lung tumors, as well, he says.
By Charlene Laino, reviewed by Brunilda Nazario, MD
SOURCES: 46th Annual Meeting of American Society of Hematology, San Diego, Dec. 3-7, 2004. Charles Sawyers, MD, Howard Hughes Medical Institute investigator; professor of medicine, University of California, Los Angeles. Stanley Schrier, MD, active emeritus professor of medicine/hematology, Stanford University School of Medicine, Palo Alto; president, American Society of Hematology. Kanti Rai, MD, vice president, American Society of Hematology; professor of medicine, Albert Einstein School of Medicine, New York. Francis Giles, MD, professor of medicine, department of leukemia, University of Texas M.D. Anderson Cancer Center, Houston.
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