Dec. 10, 2007 Relapsed chronic lymphocytic leukemia (CLL) patients who had a complete response to combination therapy that included the drug oblimersen survived significantly longer than patients treated with chemotherapy alone, a team led by researchers at The University of Texas M. D. Anderson Cancer Center reports at the 49th Annual Meeting of the American Society of Hematology.
Patients who achieved a complete response with oblimersen have survived so well that a median survival time cannot yet be calculated, but it is estimated to exceed 49 months. Those who achieved complete response with chemotherapy alone had a median survival time of 35 months.
"In a relapsed population, that's excellent survival," says lead author Susan O'Brien, M.D., professor in M. D. Anderson's Department of Leukemia. "Survival is associated with achieving complete response."
The Phase III clinical trial compared a regimen of fludarabine and cyclophosphamide (F/C) with F/C plus oblimersen. Known commercially as Genasense(r), oblimersen blocks the Bcl-2 protein, which plays a critical role in progression of chronic lymphocytic leukemia (CLL), including development of resistance to treatment.
By stifling Bcl-2, researchers believe CLL becomes more vulnerable to chemotherapy such as the F/C combination.
In a paper published in the Journal of Clinical Oncology in March, O'Brien and colleagues showed that patients who received the oblimersen combination were more likely to have a complete response (20 out of 120 patients, or 17 percent, compared to 8 out of 121 patients, 7 percent, who received only the F/C chemotherapy).
Complete response was more durable in the oblimersen-treated patients, with a median duration of at least 36 months compared with 22 months for those on F/C alone.
The question unanswered by the JCO paper was whether this advantage in complete response translated into an advantage in survival, O'Brien says.
Patients were followed for at least three years after randomization or until death or withdrawal from the study. Of the 20 oblimersen-treated patients with a complete response at the end of the first year, 12 survived at least four years. Of the eight complete responders in the other group, four survived at least four years.
The survival data confirm that complete response is a valid endpoint for clinical trials in relapsed or resistant CLL, O'Brien says.
Approval of Genasense(r), produced by Genta, Inc., for CLL is on appeal at the U.S. Food and Drug Administration.
Co-authors with O'Brien are: Joseph Moore, M.D., of Duke University Medical Center; Lily Ding, Ph.D., and Steven Novick, of Genta Inc.; and Kanti Rai, M.D., of Long Island Jewish Medical Center.
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