In Brief

From OncoLog, June 2007, Vol. 52, No. 6

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New Drug Enhances Chemotherapy’s Effects in Patients with CLL

An experimental, protein-targeting drug renders chemotherapy more effective in certain leukemia patients, researchers at M. D. Anderson report.

A recent M. D. Anderson–led study found that the agent, oblimersen (Genasense), significantly increased remission and survival rates among chronic lymphocytic leukemia (CLL) patients—primarily those who were sensitive to the chemotherapy drug fludarabine. Results of the phase III trial were published in the March 20 issue of the Journal of Clinical Oncology.

Oblimersen is known as an antisense drug—by interacting with a particular protein’s messenger RNA, it blocks production of the protein, which ordinarily protects cancer cells from chemotherapy. Drugs such as fludarabine have a better chance of killing these cells when less of the protein is present.

The study included 241 patients whose CLL was refractory or had recurred after at least one prior chemotherapy regimen containing fludarabine, a first-line drug for treating the disease. Half the patients in the study received a combination of fludarabine and cyclophosphamide, while the other half were given oblimersen in addition to the two chemotherapy agents.

Researchers then noted how many patients achieved complete response (CR) or nodular partial response (nPR), which is the same as CR except that persistent nodules are detected in the bone marrow.

CR/nPR was achieved in 17% of the oblimersen group, while the same result was seen in just 7% of the chemotherapy-only control group. The difference is statistically significant, said Susan O’Brien, M.D., professor in the M. D. Anderson Department of Leukemia and lead author of the study.

Patients who went into remission after receiving the experimental regimen had a lower rate of relapse at two years (25% compared to 75% in the chemotherapy-only group). The oblimersen-treated patients also were more likely to live longer—70% were still alive three or more years following CR/nPR, compared to 38% of patients who received chemotherapy alone.

The oblimersen regimen was particularly beneficial to patients whose cancer had gone into remission following prior fludarabine treatment. Among these chemotherapy-sensitive patients, the researchers noted a fourfold increase in the CR/nPR rate. However, outcomes did not substantially improve among those with disease previously refractory to fludarabine treatment.

“For CLL patients whose disease has progressed but who are still sensitive to chemotherapy, oblimersen may represent a new treatment option,” Dr. O’Brien said. “We think it deserves further study in this population.”

Collaborators in the study included researchers from other U.S. institutions and investigators in Canada, Poland, Argentina, and Australia.

For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.

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