Scientists presented data here today at the 40th Annual Meeting of the American Society of Hematology (ASH), demonstrating how a breakthrough new experimental compound, known as CMA-676, uses an antibody connected to chemotherapy molecules to help patients fight a virulent and often fatal form of cancer - acute myelogenous leukemia (AML). The data appeared to confirm that this novel treatment method -- "antibody-targeted chemotherapy" -- shows promising efficacy and a more tolerable side effect profile than current chemotherapy treatments.
AML is a life-threatening disease in which certain white blood cells become cancerous and rapidly replace and destroy normal bone marrow and blood cells. AML is among the most serious forms of adult leukemia, with a relatively high fatality rate. Most patients require intensive chemotherapy to achieve complete remission, and some also must undergo bone marrow transplants. Up to half of patients with AML, even after such intensive treatment, have residual leukemic cells or experience a relapse.
Because current chemotherapy drugs to treat AML are non-specific - harming good as well as bad cells - patients who are receiving standard chemotherapy become very sick. Researchers at the Fred Hutchinson Cancer Research Center, in collaboration with scientists from thirteen leading leukemia centers including, University of Chicago Medical Center, MD Anderson Cancer Center and The University of Pennsylvania Cancer Center, are working with Wyeth-Ayerst Research and Celltech PLC to study CMA-676, an antibody-drug conjugate that delivers treatment directly to the leukemia cells.
The antibody is engineered to carry just a few molecules of a new and extremely potent chemotherapy agent - from the calicheamicin family -- to selectively destroy leukemic blast cells. This approach may spare primary and vital bone marrow cells that are responsible for regenerating normal blood cells once the leukemia cells are destroyed.
A Phase I study of patients with advanced AML demonstrated early efficacy and defined the appropriate dosing regimen for Phase II studies. Promising data are now emerging from the current pivotal Phase II trial in the U.S. that involves patients following relapse after initial AML chemotherapy. A preliminary analysis of these data show that CMA-676 given alone produces a remission rate of approximately 40 percent - a rate comparable to that of standard combination chemotherapy regimens. These data also show that CMA-676 has other important advantages.
"The side effects are mild compared to standard chemotherapy," says Eric Sievers, M.D., of Fred Hutchinson Cancer Research Center. "Also, the treatment did not produce some of the more common chemotherapy-induced side effects."
Standard combination chemotherapy treatment produces significant major organ damage, and sores both in the mouth and in the intestinal tract (frequent sources for opportunistic infections). CMA-676 treatment does not produce these effects. As with all standard chemotherapy treatments, CMA-676 produces a temporary suppression of bone marrow and blood cell counts.
CMA-676 is administered as a single agent, in contrast with chemotherapy regimens that involve multiple drugs that increase the likelihood of adverse side effects and drug-drug interactions. It is administered in two IV infusions fourteen days apart, and many patients received it on an outpatient basis.
Similar studies of the new treatment are underway throughout Europe and Canada.
The above story is based on materials provided by Fred Hutchinson Cancer Research Center. Note: Materials may be edited for content and length.
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