COLUMBUS, Ohio--Research from Ohio State University points to phosphoramide mustard as the cyclophosphamide(Drug information on cyclophosphamide) metabolite with the greatest alkylating activity, and suggests that a reformulation of the chemotherapeutic agent to deliver only this metabolite could reduce toxicity without decreasing anticancer activity.
This is because phosphoramide mustard is produced at the end of the agent's activation pathway, while the chemical responsible for hemorrhagic cystitis, one of the most severe side effects of cyclophosphamide, is produced earlier in the pathway, Kenneth Chan, PhD, professor of pharmacy and internal medicine at Ohio State University's Comprehensive Cancer Center, told Oncology News International in a telephone interview.
In the study, reported in the December 15 issue of Cancer Research, blood samples from 12 patients who took cyclophosphamide were analyzed, using new methods that stabilized the metabolites and allowed them to be measured.
The next step, Dr. Chan said, is to reformulate cyclophosphamide so as to deliver only phosphoramide mustard, but effective delivery of the metabolite is hindered because of its rapid break down and elimination from the body.
Preliminary results from animal studies suggest that liposome encapsulation of phosphoramide mustard may be the answer, he said.