In a new clinical trial, scientists have found that SNS-032, one of the first in a new class of drugs that inhibit cyclin-dependent kinases, is safe and could offer a potential clinical cure for advanced chronic lymphocytic leukemia (CLL).
Cyclin-dependent kinases are enzymatic proteins that are integrally involved in cellular metabolism, renewal and signaling, and are thought to play key roles in the growth of cancers. The drug did not demonstrate any clinical effect against advanced multiple myeloma, although researchers hope it might still prove to have some benefit against this blood cancer as part of combination therapy.
“No drugs that target this cancer mechanism are on the market today. I am hopeful that larger studies will show that this targeted therapy is useful against a number of advanced B cell malignancies,” said study author Dr. David S. Siegel, Co-Chief, Multiple Myeloma, John Theurer Cancer Center at Hackensack University Medical Center. Chronic lymphocytic leukemia (CLL) and multiple myeloma are both considered B cell malignancies, as they attack these cells, also known as B lymphocytes.
Both types of blood cancer leave their victims susceptible to infections and other serious complications. While there are treatments for both cancers, there is no cure, and more effective treatments are needed.
The researchers tested the new medication on 37 patients, 19 with CLL and 18 with myeloma. All patients were given SNS-032, and all were aware of what they were taking.
To test both the drug’s safety and the best potential dose, SNS-032 was given intravenously as a “loading” dose -- an initially higher dose that is then reduced to a maintenance level -- over five minutes. This was followed by a six-hour infusion given to all patients on a weekly basis for three consecutive weeks.
One patient with CLL had more than a 50 percent 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, which is an indication of a reduction in blood cancer activity.
Looking at blood test results for the patients, the researchers found anti-cancer activity. The drug appeared to inhibit cyclin-dependent kinases 7 and 9, two of the three enzymatic proteins targeted in this study. They also caused apoptosis, or cell death, in 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. 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,” said Siegel. Preclinical studies of SNS-032 demonstrated that the drug inhibited the growth of cancer cells, and induced apoptosis, in B cell malignancies. The study was published online in the Journal of Clinical Oncology.