Martha Kerr

April 28, 2009

May 4, 2009 — Editor's note: This article has been corrected to remove the erroneous statement that REDUCE was the first trial to study chemoprevention in prostate cancer.

April 28, 2009 (Chicago, Illinois) — Results from a study of chemoprevention in prostate cancer show that dutasteride (Avodart, GlaxoSmithKline) lowers the risk for prostate cancer by a significant 23%, with risk for high-grade tumors reduced in particular, investigators reported here at the American Urological Association 104th Annual Scientific Meeting.

The Reduction by Dutasteride of Prostate Cancer (REDUCE) trial is a 4-year, international, randomized placebo-controlled trial of 8200 men from 50 to 75 years with elevated prostate-specific antigen (PSA) levels and a negative prostate biopsy at baseline. Baseline PSA levels ranged from 2.5 to 10.0 ng/mL (median, 5.9 ng/mL).

Patients were randomized to dutasteride, a dihydrotestosterone 5-alpha reductase inhibitor, 0.5 mg daily, or placebo. PSA levels were measured biennially for 4 years, and prostate biopsies were conducted at 2 and 4 years.

"There is currently no approved treatment for risk reduction in prostate cancer," lead investigator Gerald Andriole, MD, professor and chief of urology at Washington University in St. Louis, Missouri, told meeting attendees when presenting the REDUCE findings.

"After 4 years, there was an absolute risk reduction of 22.5% and a relative risk reduction of 23%," Dr. Andriole announced. There were 659 cases of prostate cancer in the dutasteride group and 857 cases in the placebo group.

The incidence of cancer by year 2 was 13.4% with dutasteride and 17.2% with placebo. By year 4, the incidence was 9.1% with dutasteride and 11.8% with placebo.

"Despite an uneven prevalence of cancer at baseline, there was still a significant 23% reduction in risk," Dr. Andriole said.

"Risk was most markedly reduced in the numbers of high-grade tumors, with absolutely no increase in incidence," he added.

"It could be that dutasteride shrinks the prostate and thereby shrinks the tumors, but it also appears that dutasteride has an effect in high-grade tumor cells in particular, through both type 1 and type 2 5-alpha reductase inhibitors," Dr. Andriole said. Type 1 receptor inhibition has a pronounced effect in high-grade tumor cells. Finasteride, which was studied for chemoprevention in the Prostate Cancer Prevention Trial (PCPT), acts only on type 2 5-alpha reductase inhibitors.

"I would recommend chemoprevention for high-risk men based on these results. It is certainly enough to convince me. I would take it," Dr. Andriole told Medscape Urology. "Any man who is at high-risk because of age, rectal exam, and PSA level . . . or has other factors, such as a high [body mass index], a family history, or other reasons for a risk of prostate cancer greater than 30% in the next 4 years is a candidate in my book."

"Isn't it possible that the PSA doesn't rise until the prostate is filled with high-grade cells, making the cancer more difficult to treat at that point?" asked William J. Catalona, MD, from the Department of Urology at Northwestern Feinberg School of Medicine in Chicago, Illinois.

"I understand the concern, but happily, the data do not support that," Dr. Andriole responded.

"Hormonal therapy is never curative," Dr. Catalona pointed out. "How long will the effects of dutasteride last?"

Dr. Andriole agreed that the drug's effects will not be permanent. He emphasized that there was no increase in the incidence of high-grade tumors, "and these tumors with Gleason scores of 8, 9, and 10 are killers," he said. "In addition, dutasteride enhances the ability of PSA [testing] to detect cancers. It makes PSA a better test," he asserted.

REDUCE was funded by GlaxoSmithKline, the maker of Avodart. Dr. Catalona has disclosed no relevant financial relationships.

American Urological Association 104th Annual Scientific Meeting: Late Breaking Abstract 1. Partial results presented April 27, 2009; full results presented April 28, 2009.

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