ANAHEIM, California—In patients with superficial bladder cancer, it is possible to optimize treatment with mitomycin(Drug information on 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.|
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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 in outcome.)
Phase III Trial
