Delivery of Effective Cyclophosphamide Metabolite Could Reduce Toxicity

COLUMBUS, Ohio--Research from Ohio State University points tophosphoramide mustard as the cyclophosphamide metabolite withthe greatest alkylating activity, and suggests that a reformulationof the chemotherapeutic agent to deliver only this metabolitecould reduce toxicity without decreasing anticancer activity.

This is because phosphoramide mustard is produced at the end ofthe agent's activation pathway, while the chemical responsiblefor hemorrhagic cystitis, one of the most severe side effectsof cyclophosphamide, is produced earlier in the pathway, KennethChan, PhD, professor of pharmacy and internal medicine at OhioState University's Comprehensive Cancer Center, told OncologyNews 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 wereanalyzed, using new methods that stabilized the metabolites andallowed them to be measured.

The next step, Dr. Chan said, is to reformulate cyclophosphamideso as to deliver only phosphoramide mustard, but effective deliveryof the metabolite is hindered because of its rapid break downand elimination from the body.

Preliminary results from animal studies suggest that liposomeencapsulation of phosphoramide mustard may be the answer, he said.