COLUMBUS, Ohio--Research from Ohio State University points to
phosphoramide mustard as the 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.