ORLANDO — Gleevec a new drug used to treat chronic myeloid leukemia (CML), is more effective and better tolerated than the current standard therapy for patients newly diagnosed with the disease.

Two years ago, this "targeted therapy" cancer drug was found to lengthen lives of patients in an advanced stage of CML.

Scientists presented their findings on Gleevec at the 38th annual meeting of the American Society of Clinical Oncology (ASCO), in Orlando, Fla.

In May of 2001, Gleevec, made by Novartis, was approved for use in advanced stages of CML after a study found it extended the lives of patients in an advanced phase of the disease. CML previously was commonly fatal within four to six months for those with an advanced acelerated phase, or "blast crisis."

At that time, Brian J. Druker, MD, the lead scientist in the development of the drug, thought the drug could be even more effective if given earlier in the disease. He and an international team of scientists from 177 cancer centers in 16 countries had begun a clinical trial testing it in patients newly diagnosed with CML.

They gave four Gleevec capsules (400 mg) daily to 553 patients, while another 553 got the standard therapy of interferon, plus the chemotherapy drug cytarabine.

At an average follow-up time of 14 months, 68% of patients treated with Gleevec had no detectable leukemia, compared to 7% of interferon-treated patients.

That shows Gleevec to be almost 10 times more effective than interferon, Druker said.

During the 14-month follow-up period, 7% of patients on interferon moved into the more advanced accelerated phase (blast crisis) of CML, compared to 1.5% of those on Gleevec, said Druker.

Patients were also better able to tolerate the Gleevec therapy than the interferon-based treatment, so by all the measures in the trial Gleevec proved better than the standard interferon-based therapy, he said.

"For these reasons, Gleevec should now be considered as the standard, first-line therapy for CML," said Druker.

The chief medical officer of the American Cancer Society (ACS) agreed.

"Now that a very large, well-controlled, randomized clinical trial has confirmed what many were predicting — that Gleevec is a superior treatment — all new patients with CML really should be treated with Gleevec as the first treatment," said Harmon Eyre, MD, the ACS executive vice-president for research and medical affairs.

Commenting on the study during the panel presentation, Stephen MacKinnon, MD, University College, London, said that it is still early in the disease process for many of the patients in this study. He emphasized that it is important to continue to study these patients carefully to determine the long-term effect of Gleevec.

MacKinnon also pointed out that the cost of treating a patient with Gleevec is estimated at $25,000 per year. Should a young patient continue to take this drug throughout his or her lifetime, it would be very expensive compared to other therapies currently available.

In response to questions about the high cost of Gleevec, Druker noted that patients on interferon are seldom able to remain active in the work force. He said that patients on interferon have severe fatigue associated with the treatment. Druker said Gleevec patients are able to be productive and provide a balance to the drug's relatively higher cost.

In another study reported at ASCO 2002, Gleevec showed the ability to shrink or stop the growth of tumors for at least a year in over 60% of patients with GIST (gastrointestinal stromal tumor). GIST is a rare stomach tumor, and prior to Gleevec it was almost always fatal.

Margaret von Mehren, MD, of Fox Chase Cancer Center in Philadelphia, and colleagues gave Gleevec pills daily to 147 patients in a Phase II clinical trial.

One year after beginning to take Gleevec, GIST tumors had shrunk by half or more in 60% of the patients and another 20% had tumors that shrank by less than that but stopped growing.

Von Mehren said tumors continued to grow in about 12% of the patients, although they originally had responded to the drug.

Studies now being conducted may help explain why those patients' tumors began growing again, she said.

"The responses we have seen in this trial are long-lasting, and far superior to those seen with chemotherapy, to which only about 5% of GIST patients respond," said von Mehren.

For those reasons, Gleevec should be the new standard treatment for patients with GIST, she said.

The very large difference in the effectiveness of Gleevec compared to chemotherapy in GIST, and compared to interferon in CML, are considered by many to be a forecast of the potential of the new class of drugs of which Gleevec is the best known, said ACS' Eyre.

These new drugs are usually referred to as targeted therapies, because they attack targets present, or abundant, only on cancer cells. This new therapy leaves normal cells largely unharmed, unlike many chemotherapy drugs, which attack all fast-growing cells, Eyre said.

That represents a new cancer treatment paradigm — a new way of thinking about how best to treat cancer, said Eyre.

Gleevec interferes with the activity of one enzyme in CML, and another in GIST, both of which send signals to the nucleus of cancerous cells, telling them to grow and divide, making more cancerous cells.

Druker says he believes the path to more success against cancer is clear.

"We hope the battle plan laid out by Gleevec will lead to a better treatment for all cancers, and I believe in the future we will see a Gleevec for all cancers," noted Druker.

That battle plan involves first determining exactly what is driving the growth of a particular cancer, then designing a drug to interfere with it, Druker said.

Eyre counts himself among those encouraged by the success of Gleevec.

"In contrast to extending a person's life two or three months, which is real progress with some drugs in some cancers, this drug and this targeted approach with other such drugs may well extend a person's longevity by years, and that is something to be excited about," said Eyre.