Drug Shows Promise against Hard-to-Treat Chronic Lymphocytic Leukemia ► NCI Cancer Bulletin for January 10, 2012 - National Cancer Institute

NCI Cancer Bulletin for January 10, 2012 - National Cancer Institute

Drug Shows Promise against Hard-to-Treat Chronic Lymphocytic Leukemia

Navitoclax, an experimental drug that inhibits a group of proteins that promote cell survival, has shown encouraging results in a phase I trial in patients with difficult-to-treat chronic lymphocytic leukemia (CLL). The drug targets several related proteins in the BCL2 family, which are present in many types of tumor cells and which block the natural tendency of abnormal cells to undergo programmed cell death, or apoptosis.

Among 26 patients who received navitoclax after their cancer had relapsed or stopped responding to other treatments, nine experienced a partial response and seven maintained stable disease for more than 6 months, an international research team reported December 19 in the Journal of Clinical Oncology. And of 21 patients with lymphocytosis (an increase in the number of lymphocytes in the blood) at the start of the trial, 19 had a reduction in lymphocyte count of at least 50 percent. The main dose-limiting toxicity was thrombocytopenia.

This study “provides the first convincing clinical validation of BCL2 as a useful therapeutic target in CLL,” wrote the authors, Dr. Andrew W. Roberts of the Royal Melbourne Hospital in Australia and his colleagues.
The response to navitoclax was “impressive” considering that the drug was given as a single agent to patients who had received multiple prior therapies, Dr. Peter Hillmen of St. James’s Institute of Oncology in the United Kingdom commented in an accompanying editorial.

The strategy of inhibiting anti-apoptotic BCL2 family members “seems likely to herald the beginning of a revolution in the treatment of CLL,” Dr. Hillmen continued. He added that navitoclax is one of several investigational agents now in clinical development that target different aspects of CLL biology. The next steps, he went on, are to determine how to combine these new agents most effectively. “The logical combination of these agents promises to dramatically alter the treatment of CLL and may eventually lead to therapy that is both more effective and less toxic,” he wrote.

Previous phase I studies have demonstrated the safety and preliminary efficacy of navitoclax in patients with difficult-to-treat lymphomas and small-cell lung cancer, wrote Dr. Loren D. Walensky of the Dana-Farber Cancer Institute in an accompanying article describing the biological pathway of navitoclax in CLL. The drug now “advances to phase II testing as a single agent and in combination to combat cancer chemoresistance, he noted.