Drug Benefits Chronic Lymphocytic Leukemia
CancerWise - May 2007
The experimental drug oblimersen (Genasense®) shows benefit for patients with chronic lymphocytic leukemia (CLL) whose disease has progressed, but who are sensitive to the chemotherapy drug fludarabine, according to results of an international clinical trial.
Significance of results
“Oblimersen could become a new treatment option for this population of patients,” says the study’s lead author Susan O’Brien, M.D., a professor in M. D. Anderson’s Department of Leukemia.
M. D. Anderson led the phase III study, published in the March 20 issue of the Journal of Clinical Oncology, that included investigators from the United States, Canada, Poland, Argentina and Australia.
Trial investigators enrolled 241 patients at cancer centers worldwide.
Patients received either of the following:
- Fludarabine and cyclophosphamide chemotherapy
- Fludarabine, cyclophosphamide and oblimersen
M. D. Anderson researchers found that oblimersen produced a fourfold increase in “CR/nPR” (a clinical response defined by no definitive evidence of disease) in patients who responded to fludarabine compared to patients who no longer responded to fludarabine.
Researchers found that CR/nPR was achieved in:
- 20 of 120 patients (17%) in the oblimersen group
- 8 of 121 patients (7%) in the chemotherapy group
CR/nPR was associated with the relief of CLL symptoms for at least 180 days. That includes fever, night sweats, fatigue and abdominal discomfort.
Although the overall response rate was not significantly different between the two groups, maximum benefit was observed in fludarabine-sensitive patients, O’Brien says.
This group included 51 patients in the oblimersen group and 50 patients in the group treated with chemotherapy alone, according to researchers.
Median patient survival without CR/nPR was:
- 33.8 months in the oblimersen group
- 32.9 months in the chemotherapy group
Survival for patients with CR/nPR in the oblimersen group was greater.
Median CR/nPR survival was 36 months or more in:
- 70% in the oblimersen group
- 38% in the chemotherapy group
“Patients who were previously refractory to fludarabine (failed to respond to a prior fludarabine-based regimen or had progressed within six months of treatment) did not benefit substantially from the addition of oblimersen,” O’Brien says. “Also, because there were so many refractory patients in both arms of the trial, the survival curves were not significantly different between the groups.”
Fludarabine is a newer chemotherapy drug that is now being used as a primary treatment for many patients.
Oblimersen interferes with the production of Bcl-2, a protein that can stop a cell from destroying itself. Bcl-2 is often over-produced in cancer.
Oblimersen was submitted for U.S. Food and Drug Administration approval for the patient population in this trial (patients whose CLL had progressed or relapsed), but the drug application was denied. Last month, however, Genta Incorporated, the biopharmaceutical company that manufactured the drug submitted an appeal for approval.
In the meantime, the company is considering whether to pursue a follow-up phase III trial previously approved by the FDA, targeting patients whose disease has not progressed, O’Brien says.
– From staff reports
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