ASCO PROSTATE: Prostate Cancer Prevention Role Seen for BPH Drug

KISSIMMEE, Fla., Feb. 22 -- Dutasteride (Avodart), a drug used to treat benign prostatic hyperplasia, may also prevent the development of prostate cancer by inducing genetic changes at the cellular level, researchers reported here today.

"Our primary finding is that several genes potentially involved in prostate cancer development and progression appear to be favorably altered by treatment with the 5-alpha-reductase inhibitor dutasteride," said Elahe Mostaghel, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle.

Essentially the investigators found that neoadjuvant use of dutasteride led to postsurgical cellular changes that they hope will turn out to retard prostate disease, However, they conceded that the implications on these findings were speculative.

Reported the findings at a prostate cancer symposium here, Dr. Mostaghel and colleagues analyzed gene expression in tissue samples from a small study that compared neoadjuvant dutasteride followed by prostatectomy with prostatectomy alone.

Twenty-six men were randomized to 0.5 mg of dutasteride and 24 to 3.5 mg of dutasteride daily for four months before surgery. Twenty-five men had surgery alone. Gene expression profiling was performed, finding 32 unique genes that were upregulated by treatment with dutasteride and 98 genes that were down regulated.

From that group of genes, the researchers said they found at least three specific genes that may play a major role in cancer development: IGEBP3, TMPRSS2, and TFF3.

She said that IGEBP3, which appears to be upregulated by dutasteride, promotes apoptosis and inhibits cell proliferation. Previous studies have reported that the expression of this gene is decreased in patients with prostate cancer.

The other two genes-TMPRSS2 and TFF3-both appeared to be downregulated.

Dr. Mostaghel said TMPRSS2, which is regulated by androgen, promotes the growth of prostate cancer by fusion with oncogenes, while TFF3 blocks apoptosis and promotes invasive activity. In addition to its role in prostate cancer, TFF3 is overexpressed in breast cancer and gastrointestinal cancers.

But she urged caution in interpreting the results, noting that "patients in the study were only treated for a limited period." The findings need to be evaluated in a larger trial with longer treatment duration.

She said that studies to look at those long-term relationships are under way.

The Prostate Cancer Symposium is cosponsored by the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.