J. Curtis Nickel, MD, who led a multicenter, randomized, placebo-controlled study of pentosan polysulfate (Elmiron) in men with CPPS, sees two reasons why the therapy reached only borderline statistical significance.
Significant number of responders The study, published in the Journal of Urology (2005; 173:1252-5), included 100 men with CPPS randomized to receive placebo (49 patients) or pentosan polysulfate, 300 mg (51 patients) three times daily for 16 weeks-triple the usual dose used in IC. The primary outcome was improvement on the Clinical Global Improvement (CGI) scale (a seven-point global response assessment), and additional outcome measures were the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) and the Subjective Global Assessment and Symptom Severity Index.
Mean improvement on the CGI scale (response rated on a scale of 1 through 7) was not significantly different between the treatment and placebo groups, but significantly more patients receiving active treatment were classified as responders, defined as those patients who experienced moderate to marked improvement (18 or 37% vs. eight or 18%, p=.04).
"The numbers are not a lot different from what we have seen in IC," Dr. Nickel pointed out.
In IC studies, he said, the response rate for pentosan polysulfate was in the high 30% range, and the response for placebo was 16% to 18%.
The change on all the different domains of the NIH-CPSI suggested some effect, although most domains did not reach statistical significance. The one domain that did was quality of life. The dropout rate was fairly high-11 patients in the treatment group and four in the placebo group-because of adverse events and intercurrent illness. The most common adverse events were diarrhea, nausea, and headache.
Men may have IC instead The investigators were unable to tease out why the men who experienced modest or marked improvement did so.
With the relative small number of patients and the high dropout rate, Dr. Nickel explained, it wasn't possible to stratify the results to determine whether those men who did better had significantly higher scores on NIH-CPSI questions related to irritative urinary symptoms than on other domains. That might have been a clue that those men may have had IC.
Larger studies with smaller doses might be able to uncover those relationships. In the current study, the investigators used a high dose because they didn't want to miss an effect. Dr. Nickel now knows from forthcoming published studies that increasing the dose of pentosan polysulfate does not increase efficacy in IC; the high dose just increases adverse reactions and toxicity.
Dr. Nickel said he does use pentosan polysulfate in men, but "at the present time, patients in my practice who get it are the patients who are referred to my prostatitis clinic who I feel more aptly fit a diagnosis of IC."
Making the distinction How does he make the distinction?