An American Cancer Society (ACS) expert says this finding could set a new treatment standard for patients with non-aggressive bladder cancer who are at high risk for recurrence of the disease.

Treating superficial bladder cancer by infusing mitomycin C directly into the bladder has been used for several decades, but the response has been hit or miss at best, ranging from 2% to 40%. Finding out why the therapy sometimes worked and sometimes failed miserably was part of the impetus for the research, says by Jessie L. -S. Au, PharmD, PhD, lead author of the study.

"We set out to find out why there was such variability and found two main reasons – the inability to deliver the drug in the highest possible concentration to the tumor site, and the biology of the tumor that makes it less sensitive to the drug. We can’t change the second one, but we found out that the problem with the delivery of the drug was quite simple," says Au, who is a distinguished professor at the University of Ohio and the Dorothy M. Davis chair in cancer research.

"In the past, physicians didn’t know exactly what the maximum possible dose was in the bladder. What these authors have found is that if you work to get the best optimal dose inside the bladder you can actually achieve a better outcome," says Harmon Eyre, MD, ACS chief medical officer, who calls this an important study.

In order to optimize the drug’s potential, the researchers altered five variables:

• increased the dose to 40 mg.
• reduced the amount of fluid in which the drug is dissolved.
• prohibited fluid intake before and during the treatment, to reduce excess urine in the bladder.
• further reduced urine in the bladder with a catheter immediately prior to treatment.
• reduced the acidity of the urine with oral doses of sodium bicarbonate before treatment, because mitomycin C is unstable in acidic urine.

All the patients in the 14-center, multinational trial were considered at high risk for cancer recurrence and were followed over the course of five years.

Compared to the 111 patients who received the standardized dose of mitomycin C, the 119 patients receiving the optimized dose had significantly better outcomes. They had a longer time to recurrence: 29 months, compared to 12 months for the standardized group. At five years, 41% of the patients receiving the optimized mitomycin C were recurrence-free compared to 25% in the standard treatment group. Side effects of the two treatment methods were comparable.

In an accompanying editorial James E. Montie, MD, writes that the authors’ choice to "go for the home run" produced enough change to provide a detectable effect given the small number of patients in the trial.

Au says that by using a computer model to determine what effect incremental changes would have, the researchers hypothesized that changing all variables at once would give a 20% to 40% benefit. "So we deviated from the norm of traditional clinical trials, but we think the benefit is great," she says.

Though optimized mitomycin C therapy may give clinicians another option in treating this disease, according to Au, the data presented in the study should not be extrapolated to higher-grade, more aggressive forms of the disease, Montie writes in his editorial. The study is based on good research and it would be reasonable to integrate the optimized therapy for treatment of low grade disease, he says.

"This article is probably the best study to demonstrate the value of the therapy and I think it will set the standard of the technique for using this therapy until something better comes along," says Eyre.