'Immediate Hope' for Leukemia Patients
2 New Drugs Fight Chronic Myeloid Leukemia; Drug Cocktail in Future?
June 14, 2006 - Two new drugs -- developed with astonishing speed -- offer
real hope to patients with deadly forms of leukemia.
Chronic myeloid leukemia (CML) is a fatal blood cancer. It can occur when
two chromosomes swap genetic material. This swap results in a distorted
chromosome -- dubbed the Philadelphia chromosome -- which causes the bone
marrow to have deadly, uncontrolled overgrowth of white blood cells. This also
causes another fatal cancer: Philadelphia chromosome positive acute
Five years ago, scientists came up with a major breakthrough: Gleevec, the
Novartis drug that blocks the action of the abnormal chromosome. But over five
years, one in five patients becomes resistant to Gleevec. The result:
Now, in an unusually rapid payoff from basic science, researchers have come
up with two new drugs that work when Gleevec doesn't. One is nilotinib from
Novartis, a second-generation offshoot of Gleevec. The other is Sprycel, a new
drug from Bristol-Myers Squibb. Novartis and Bristol-Myers Squibb are WebMD
Fast Track for Approval
Early clinical trials of nilotinib and Sprycel were supposed to judge only
the drugs' safety. But patients did so well in these studies that the drugs are
now on the fast track for approval. Results of both studies appear in the June
15 issue of The New England Journal of Medicine. So does an editorial
by Brian J. Druker of the Oregon Health and Science University.
The reports "provide immediate hope for patients in whom CML cells have
developed resistance to [Gleevec]," Druker writes. "The good news for
patients with CML is that the long-term prospects for control of the disease
There's more good news. Doctors have found that patients do best when
Gleevec has a very powerful initial effect. Both nilotinib and Sprycel are more
powerful than Gleevec -- suggesting that patients may do best if started out on
one of these new drugs.
Better still, Druker suggests, is if two or three of the drugs could be
combined into a superpotent drug cocktail.
There are, however, downsides. Nilotinib appears to cause heart rhythm
problems in some patients. And Sprycel causes patients to gather fluid around
the outside of the lung. A drug cocktail would work only if it had manageable
And there's one more problem. There's one mutation to the Philadelphia
chromosome that resists all three drugs. Patients with that mutation would
still be at risk of fatal leukemia. Even so, Druker says scientists should be
up to the task of creating yet another drug to target this triple-resistant
The Sprycel study included researchers Charles L. Sawyers, MD, of UCLA, and
The nilotinib study included researchers Hagop Kantarjian, MD, of Houston's
M.D. Anderson Cancer Center, and colleagues.