ANAHEIM, CaliforniaIn patients with superficial bladder cancer, it
is possible to optimize treatment with mitomycin (Mutamycin) by enhancing the
drug concentration in urine, according to the results of a multicenter study
presented at the American Urological Association annual meeting (abstract 776).
Experimental studies have shown that the incomplete and variable responses
to mitomycin occur because of two problems: inadequate delivery of drug to the
tumor site and insensitivity of the tumor to the drug. The current study
addressed inadequate drug delivery, identifying several contributing factors
and constructing a strategy to overcome them.
Principal investigator Jesse L-S Au, PhD, of Ohio State University,
Columbus, pointed out that suboptimal concentration of mitomycin and inadequate
emptying of the bladder are major problems leading to dilution of the drug and
therefore diminished efficacy.
"Patients often do not have fully emptied bladders. The volume of the
dosing solution is 20 mL, and some patients retain 4 or more ounces of
urine," she said. "They also continue to consume beverages, which
leads to further dilution of drug concentration." The other problem is
that mitomycin is acid labile, meaning that it is degraded 12 times faster at
below neutral pH than at a pH of 7.
The investigators determined six parameters that could be changed to
potentially maximize drug delivery to the tumor . They
then performed a computer simulation, using a standard mitomycin protocol and
changing one parameter at a time to predict the effect on outcome.
"If we increased the dose, we increased the recurrence-free rate from
20% to 25%. Then if we drained the bladder completely, we got another 5%
increase. In the end, we concluded that if we changed five factors, we could go
from a 20% recurrence-free rate to a 40% rate," Dr. Au said. (The sixth
factor, increasing treatment duration from 2 to 4 hours, showed no improvement
Phase III Trial