Antileukemia Drug Shows Promise in Phase I Clinical Study

A Phase I clinical trial has demonstrated the safety and potential effectiveness of the cyclin-dependent kinases inhibitor SNS-032 for treating advanced chronic lymphocytic leukemia (CLL).

SNS-032 is a highly selective and potent inhibitor of cyclin-dependent kinases (Cdks) two, seven, and nine, with in vitro growth inhibitory effects and ability to induce apoptosis in malignant B cells. To see whether these attributes would apply to the human disease, investigators at Hackensack University Medical Center (NJ, USA) used the drug to treat 37 patients, of which 19 with CLL, and 18 with myeloma. All patients had advanced disease that was in relapse, and all had been through an average of four previous treatments with other medications.

The patients were treated with SNS-032 in a regimen comprising a loading dose followed by six-hour infusion weekly for three weeks of each four-week course. Results published in the May 17, 2010, online edition of the Journal of Clinical Oncology revealed that one CLL patient had more than a 50% reduction in measurable disease, but no improvement in disease markers in the blood. Another CLL patient had stable disease for four courses of treatment. For multiple myeloma, two patients had stable disease with treatment and one had normalization of spleen size, an indication of a reduction in blood cancer activity. At the molecular level, the drug inhibited cyclin-dependent kinases seven and nine, which triggered apoptosis in the cancer cells.

"Our study found that this drug is well tolerated and had some clinical effect, but it is important to note that this was a small, very early stage study,” said contributing author Dr. David S. Siegel, chief of the division of multiple myeloma at Hackensack University Medical Center. "Based on these findings, there is justification for additional research, which will show whether this drug has a place in the arsenal of treatments for hematologic malignancies. The results of the preclinical studies suggest that we might see more antitumor effects if the drug is given over a longer period, possibly eight hours or more. Because the patients in the study were at a late disease stage and heavily pretreated, we might also see more of a response in earlier-stage patients. Future studies could look at these issues, as well as the feasibility of using SNS-032 in combination with other therapies."

"No drugs that target this cancer mechanism are on the market today,” said Dr. Siegel. "I am hopeful that larger studies will show that this targeted therapy is useful against a number of advanced B cell malignancies.”

Related Links:
Hackensack University Medical Center