WEDNESDAY, Feb. 27, 2002 (HealthDayNews) -- The cancer drug Gleevec is living up to its billing in patients with leukemia who have failed to respond well to conventional therapy. In fact, doctors say, less than a year after winning regulatory approval Gleevec has become the treatment of choice for people with chronic myelogenous leukemia.
A new study, which appears this week in the New England Journal of Medicine, shows that after 1.5 years of treatment the drug's success rates are as encouraging as they had been in the short run.
Dr. Hagop Kantarjian, a leukemia specialist at the M.D. Anderson Cancer Center in Houston and the study's lead author, said the long-term follow-up data are clear: "Gleevec is quite safe and very effective."
Chronic myelogenous leukemia (CML) affects roughly 5,000 Americans a year. The average patient lives about six years with the disease, although some may survive for decades.
Until only recently, doctors used the drug interferon alfa to kill cancerous marrow cells. But this compound also destroys healthy cells and is thus extremely hard to tolerate.
Gleevec, sold by Novartis Pharmaceuticals of East Hanover, N.J., is a small molecule that targets a renegade, fused protein called BCR-ABL, which only cancerous cells produce. As a result, experts say, its side effects, which include nausea, vomiting, swelling, and diarrhea, are generally milder than those of other treatments.
Gleevec, or imatinib mesylate, was approved last May with great fanfare. Health and Human Services SecretaryTommy Thompson took the highly unusual step of holding a press conference to announce the drug's approval.
In the latest study, Kantarjian and his colleagues in the United States and Europe followed 454 patients with confirmed chronic CML who'd failed to improve on interferon. On 400 milligrams a day of Gleevec, 95 percent of patients had complete retreat of cancerous cells from their blood, and 60 percent had full or partial elimination of cancer-causing chromosomes.
After an average of 18 months, nearly 90 percent of patients had not gone on to experience acute bouts of leukemia since starting treatment, and 95 percent were still alive.
In a footnote to the study, the researchers said that an even longer look at 149 other patients found that nearly half had completely normal chromosomes 26 months after starting the drug, while 64 percent had significant or full responses to treatment. Of the initial group, nine died of their cancer and four died of other causes, giving a two-year survival rate of 92 percent.
Novartis is not yet allowed to say that Gleevec prolongs survival, since at the time of its approval there was no direct comparison with interferon to prove such a benefit. However, Kantarjian, who is conducting such a study, said he's convinced it does help patients live longer. "We have already preliminary data that shows that Gleevec is demonstrating better results," he said.
Alan Kinniburgh, vice president of research at the Leukemia and Lymphoma Society, said his group is "very excited" by the new study.
"Gleevec now appears to be a more effective and less toxic treatment for CML" than other therapies, Kinniburgh said, noting that only 2 percent of patients dropped out of the trial because of side effects.
The cancer foundation has given $7.5 million to researchers to study Gleevec, both alone and in combination with other leukemia treatments, in the hopes that remission rates can be raised above 90 percent.
Earlier this month, the FDA also approved Gleevec for treating gastrointestinal stromal tumors (GIST), a rare form of solid cancer that affect about 5,000 Americans a year. These tumors generally are born in the stomach or intestines and spread into the abdomen or pelvis.
Underscoring its versatility -- and perhaps inflating expectations -- the drug is now in various stages of clinical trials to treat a catalog of unusual cancers. These range from tumors in the brain and bone to those in the skin and eyes. The common thread of these diseases is that the abnormal cells express a variety of signaling proteins that Gleevec also hits.
Kantarjian cautioned that the results of these trials will likely fail to live up to the drug's performance in CML. "I think the realistic expectation is that Gleevec is quite effective in [CML and GIST], but it may have modest or no activity in the other" cancers. Despite its excellent performance against CML, he noted, it doesn't appear to be active against other forms of blood cancer.
Dr. David Parkinson, vice president for clinical research at Novartis, was also cautious. "We are developing this drug in other tumors with very specific biological targets in mind," he said. "It's going to take some time to sort all of this out."
Although Gleevec's side effects tend to be milder than interferon's, it is not entirely benign. Doctors at the Mayo Clinic in Rochester, Minn., for example, report this week in the New England Journal of Medicine that three patients who had taken Gleevec suffered ruptured spleens after stopping treatment. And Australian scientists, writing in the same publication, said the drug appeared to be highly toxic to one man's bone marrow.
Dr. Michelle Elliott, a Mayo researcher and co-author of the journal letter about the spleen problems, said she doesn't believe the damage was the result of taking Gleevec. Kantarjian agreed, and added that none of the patients in his study suffered similar complications, though 10, or 2 percent, did show signs of enlargement of the organ.
The Australian researchers, from Newcastle Mater Hospital, wrote that Gleevec may be responsible for the bone marrow problem. Kantarjian, however, said he has seen no evidence that the drug is toxic to normal bone marrow.
What To Do
To learn more about chronic myeloid leukemia, try the CML Support Web site. You can also visit CancerBACUP.
Read more about Gleevec from the Food and Drug Administration.