The new method achieves more predictable, stable drug levels in patients than the current method and could eventually allow doctors to more accurately adjust doses to accommodate individual differences in metabolism, thus increasing treatment effectiveness while avoiding side effects, said University of North Carolina at Chapel Hill researchers.
The findings were presented at the 2005 annual meeting of the American Society of Clinical Oncology, held May 13 through 17 in Orlando, Fla. The drug busulfan is used in leukemia patients to kill cancerous cells before bone-marrow transplant. Currently, it is administered in intermittent intravenous doses, typically via two-hour infusions of the drug every six hours. Previous studies have reported that frequent dose adjustments are needed to maintain the desired level of drug in patients and that metabolism of the drug varies from patient to patient.
"The new continuous-infusion method achieved more predictable levels of the drug than does the usual delivery method," said Dr. Thomas C. Shea, professor of medicine at UNC, director of the Bone Marrow Transplant Program at the UNC Health Care System and a member of the UNC Lineberger Comprehensive Cancer Center.
"In the relatively small number of patients tested with continuous infusion, there didn't appear to be a change in concentration or clearance of the drug during the 90-hour infusion period."
In 12 patients scheduled for bone marrow transplants, UNC researchers administered a single busulfan test dose of 0.8 mg/kg adjusted body weight over two hours. Blood concentrations of the drug were measured every two hours for eight hours following that test dose.