Scientists Study Novel Treatment For Leukemia

The findings were presented at the American Association for Cancer Research/National Cancer Institute/European Organization for Research and Treatment of Cancer Molecular Targets meeting in Miami Beach, October 31-November 2.

The treatment, one of a growing number of molecularly-targeted therapies, involves a drug called Genasenseä (formerly G3139), a compound that blocks the production of Bcl-2. Bcl-2 is a protein that is overexpressed in many cancers of the blood and other hematologic disorders. It inhibits apoptosis, or the normal way cells die, thus enabling cancer to grow out of control.

Dr. Guido Marcucci, a member of the Molecular Biology and Cancer Genetics Program at the OSUCCC and the leader of a Phase I trial evaluating Genasense at the Arthur G. James Cancer Center and Richard J. Solve Research Institute at Ohio State, says nearly half of the 20 patients in the trial responded favorably to the drug.

"There is too much Bcl-2 in many forms of acute leukemia, and we think this is why chemotherapy does not work for some patients," says Marcucci. Marcucci says Genasense cripples the production of Bcl-2, making it easier for standard chemotherapy to do its job.

Patients on the trial took a continuous infusion of Genasense for ten days, and on day six, incorporated two chemotherapy agents, cytarabine and fludarabine, as well. Marcucci says the trial included only patients with refractory or relapsed leukemia - those who had been previously treated with chemotherapy, yet who showed no improvement.

"These patients are typically very hard to treat," he says, "and can die in a matter of weeks." (more)

Of the 20 patients enrolled in the trial, nine responded favorably. Seven of those had a complete remission, and two had no evidence of disease, but failed to regain normal blood counts. Side effects of the treatment included fever, nausea, vomiting, and fluid retention, in addition to the expected side effects of chemotherapy.

" This study shows that Genasense, when combined with intensive chemotherapy for acute leukemia, is safe and able to induce disease remission," says Marcucci. "It is very encouraging that two of the nine patients who responded to the regimen are still alive and disease-free more than one year after completing treatment," he adds.

Genasense, made by Genta, Inc., is also being used in trials to treat melanoma and multiple myeloma. It has been granted "fast track" status by the Food and Drug Administration, a designation reserved for drugs that appear promising in the treatment of fatal or life-threatening conditions. Marcucci says plans are underway for larger trials at Ohio State to determine the most effective combination of Genasense and other chemotherapeutic agents.

The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, part of the Comprehensive Cancer Center at The Ohio State University, is the only free-standing cancer hospital in the Midwest. It is a national and international leader in translational research and clinical care, and one of the charter members of the National Comprehensive Cancer Network. It has consistently been ranked one of the nation's best hospitals by U.S. News and World Report.