Risks of Cancer Drug Explored: Study Says Gleevec, a Treatment for Leukemia, Could Be Toxic and Lead to Heart Failure in Patients

By Delthia Ricks, Newsday, Melville, N.Y.

Jul. 24–Gleevec, the breakthrough cancer drug that helped usher in a new generation of cancer therapies, may be toxic to the heart, researchers have found in an analysis of the drug released yesterday.

Just a month ago at the world’s largest meeting of cancer specialists, doctors waxed ecstatic about Gleevec, a medication they say has transformed chronic myeloid leukemia, a once inevitably fatal form of cancer, into a treatable disease.

Indeed, Dr. Brian Druker, the physician-scientist who helped develop the drug, told doctors at the American Society of Clinical Oncology in Atlanta last month that a majority of patients who take Gleevec can be assured of being alive five years after beginning the therapy, and that reaching a 10th anniversary on the drug appears very likely.

But Dr. Thomas Force, a professor of medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia, has found in studies of both human heart cells and mice that Gleevec can cause heart failure.

Writing in the journal Nature Medicine, Force said his study grew out of a report about 10 Gleevec patients at M.D. Anderson Cancer Center in Houston who developed heart failure. The cases were first reported by Anderson and the drug’s maker, Novartis Pharmaceutical, last year.

“Prior to going on Gleevec, they were all normal, but within one to 14 months, they all presented with serious heart failure, and there were no major [cardiac] events that could have explained it,” Force said.

What it’s intended to do

Gleevec, one of the first in the growing class of targeted cancer drugs, is a dramatic departure from chemotherapy. It targets the lone biochemical miscue that leads to the leukemia: an abnormal fusion of an enzyme dubbed ABL-tyrosine kinase to a protein called BCR. The fusion forces the enzyme into wild overdrive. Gleevec blocks the enzyme, but is not a cure.

Force theorizes that Gleevec interferes with the enzyme’s role of maintaining healthy heart function.

Novartis Pharmaceuticals, Gleevec’s maker, said in a statement Friday that heart failure is not a new discovery and is noted as a side effect of the drug. While the disorder is possible, company officials said, it is extraordinarily rare. Gleevec, a two-pill-a-day regimen, was approved by the Food and Drug Administration in 2000.

Dr. Michael Deininger, a professor of medicine at Oregon Health and Science University, where clinical studies of Gleevec were conducted prior to approval, said heart failure has not been a widely recognized problem in the thousands of people who have taken the medication globally. Deininger said he and his colleagues, which include Dr. Bruker, have never seen a case of heart failure at their center.

He acknowledges, however, that one of the drug’s leading side effects — lower extremity swelling — is identical to a hallmark symptom of heart failure. “Edema is more recognized in very sick patients,” taking the drug, he said of those with late-stage leukemia.

By the numbers

An estimated 5,000 people in the United States develop chronic myeloid leukemia annually. But more than 1 million people are hospitalized for heart failure, a major public health issue and a leading cause of death.

Dr. George Demetri, director of the Ludwig Center at the Dana Farber Cancer Institute in Boston, said Force’s study should not revive memories of Vioxx, a Merck product withdrawn from the market in September 2004 after findings it caused heart attacks. Instead, he explained, it reveals how a potent cancer drug can have an effect in otherwise healthy tissue.

“We are really on the doorstep of a new era in medicine, and I don’t have the arrogance to say we have figured it all out,” Demetri said. “We are treating cancer in a new way, and along the way we will learn things that will inform us about other organs in the body.

“This is a cancer drug and is given to people with a life-threatening disease, so there is a risk-benefit tradeoff,” Demetri said. “We have been following patients who absolutely would have died back in 2000 and now have been going strong for six years.

“Are there side effects? Of course there are.”

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Copyright (c) 2006, Newsday, Melville, N.Y.

Distributed by McClatchy-Tribune Business News.

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