New drug may give O'Neal's story a happy ending

By Adele Slaughter, Spotlight Health

With medical adviser Stephen A. Shoop, M.D.

	AP file
	Ryan O'Neal.

Actor Ryan O'Neal gained fame in the '70s in the movie Love Story, in which he played the true love of a girl who develops acute leukemia. Now, 30 years later, his own life has taken a tragic twist: O'Neal has been diagnosed with chronic myelogenous leukemia (CML).

But O'Neal's story may have a happy ending, says a leading leukemia expert.

Research indicates that a new drug called Gleevec inhibits the growth of cancerous cells without attacking the body's healthy cells. The Food and Drug Administration (FDA) is reportedly close to approving Gleevec, which has generated very promising preliminary results in trial studies.

"There's a very good chance this drug could put Mr. O'Neal into remission," says Dr. Charles Sawyers, professor and researcher at UCLA's Jonsson Cancer Center. Sawyers emphasizes he is not treating the actor, who last week revealed his illness.

Leukemia is a cancer associated with the body's white blood cells. It begins in either the bone marrow or the lymphatic system, eventually spreading to other organs. Leukemia can be chronic (slow growing), or acute (rapidly growing).

Chronic myelogenous leukemia (CML), one of the four major types of leukemia, is the most rare and generally only affects adults. CML begins as a slow-growing cancer and becomes acute in the later stages of the disease.

The American Cancer Society estimates that about 4,700 Americans will be diagnosed with CML this year. Statistically, approximately half of those cases result in death.

But that may be about to change.

Leukemia basics

			Leukemia symptoms
			• Chronic fatigue • Fever of unknown origin • Frequent bacterial or viral infections • Weight loss not due to dieting or exercise • Headaches • Skin rash • Non-specific bone pain • Bruising easily • Bleeding from gums or nose • Blood in urine or stools • Enlarged lymph nodes and/or spleen • Abdominal fullness/bloat

About one out of every five people with chronic leukemia have no symptoms in the early stages of the disease. Even more troublesome is the fact that the manifesting symptoms of leukemia can be unclear, making early diagnosis difficult. Patients may have some or all of a number of symptoms.

Doctors commonly diagnose leukemia through history, physical examination, and repeated blood cell counts. Normal white blood cells are used to fight infections in the body. Without the proper white cell count — about 6,000 to 10,000 — or with abnormal white cells, the immune system defenses are weakened against bacteria and viruses. For a leukemia patient, a common cold can be extremely debilitating or even fatal.

An individual with CML produces an abundance of "irregular" white blood cells. Eventually, these proliferating white blood cells clog the bloodstream with immature cells, crowding out the healthy cells in the bone marrow and the blood becomes "goopy."

Bone marrow tests, excisional lymph node biopsy, lumbar puncture as well as X-rays, CT, MRI and ultrasound imaging tests may also help confirm a diagnosis and define the stage of the condition.

Doctors recognize three stages of CML: the "chronic," the "accelerated," and the end stage, referred to as "blast crisis." During the chronic stage, white blood cell counts peak, but generally patients have very few symptoms. The chronic stage of CML can last up to five years. During the accelerated stage of CML, blood cell counts skyrocket and symptoms abound. At the blast crisis stage the patient's prognosis is grim. Generally, they live only several months.

Experts agree that the abnormal gene that causes CML is acquired, not inherited. However, it is not clear why the gene begins to mutate. The American Cancer Society confirms that some risk factors for contracting leukemia are smoking and increasing age.

Environmental factors can also play a role. For example, the survivors of the Hiroshima and Nagasaki nuclear blasts have a high incidence of CML. There is also concern that very high-voltage power lines might cause leukemia.

But most people who develop leukemia do not have any of the known risk factors.

Miracle treatment

			For more information
			• American Cancer Society • UCLA Jonsson Cancer Center

"Biologically, CML is caused by a mutant protein that we have been studying for a long time," says Sawyers, who has studied CML for more than a decade. "It involves an enzyme called tyrosine kinase, a class of enzyme which cancers frequently create in the body. We thought that if we could find a way to inhibit the growth of these enzymes we could fight this particular mutant protein."

The two standard treatment options for CML have been either a bone marrow transplant, which has extreme limitations, or a daily injection of the drug interferon. Both treatments are extremely taxing for patients.

"Interferon causes fevers and makes patients feel as if they have the flu. It can also cause depression," reports Sawyers. "While it can help, it severely diminishes the patient's quality of life."

But now there is an alternative with minimal side effects. Originally known by its chemical compound number — STI-571, Gleevec is creating new options and hope for those with CML.

"I worked with Gleevec from the very beginning and it's amazing how well it works," says Sawyers, who ran trial studies at UCLA's Jonsson Cancer Center. "It appears that this new drug actually does inhibit the activity of the enzyme or mutant protein, tyrosine kinase, which in many patients kills the leukemia."

In clinical trials that began in June 1998, STI-571 was tested with patients in the chronic stage of the disease. "In the past four years at our clinic at UCLA we have had a 98% response rate," says Sawyers. "In the first trials we tested 80 or so people and in the second trials there were 1,000 patients using STI-571."

In another trial, patients with end stage leukemia were tested. Eleven percent of those being treated with Gleevec had their blood count return to normal.

"Of course, the biggest unknown is what are the long-terms results of taking Gleevec," says Sawyers.

Bob Ferber, prosecutor for L.A.'s City Attorney's office, is one of Sawyer's patients who is in full remission.

"I was critical. When I learned that I was in remission, I cried," Ferber says. "I found myself wishing that my friends in the support group could have this too," says Ferber. "Even if all I got was these past 15 months, it was worth it for the improved quality of life."

Gleevec also has shown signs of successfully treating a rare stomach tumor, and likely can be used in combination with other drugs for other life-threatening diseases such as Hepatitis C.

"The success of this drug will inspire efforts to design other inhibitors for other kinds of cancer," predicts Sawyers. "This is the highlight of my career. I have been waiting to see patients get better — not just survive."

Now CML patients are hoping the FDA agrees with Sawyers and approves the drug soon. For O'Neal, approval could mean a starring role in a real 'love story.'

More Spotlight Health stories