Combination therapy significantly delays progression of benign prostatic hyperplasia

December 17, 2003

A five-year, multicenter study, published today in The New England Journal of Medicine, provides the first scientific evidence that combining alpha-blocking doxazosin with the drug finasteride is significantly more effective than using either treatment alone, said Dr. John McConnell, UT Southwestern's executive vice president for health system affairs and lead author of the study. The clinical trial involved more than 3,000 men and 20 major medical centers across the United States and is the largest study of its kind ever conducted.

Use of finasteride alone or the combination therapy significantly reduced the risk of acute urinary retention and the need for surgical intervention. A surprising finding of the study was that the alpha blocker doxazosin was not effective in reducing the long term risk of acute urinary retention or need for surgical therapy.

"Although we had predicted that combination therapy would be more effective than either drug alone, the magnitude of risk reduction was surprising," said Dr. McConnell, the former UT Southwestern chairman of urology who is internationally known for leading the development of clinical practice guidelines for the treatment of BPH in 1994. Dr. McConnell also directs the National Institutes of Health's George M. O'Brien Urologic Research Center at UT Southwestern.

These findings culminate three decades of research at UT Southwestern that began with Dr. Jean Wilson's discovery of the role of the enzyme 5-alpha reductase in benign growth of the prostate. The enzyme would later be the target for the drugs finasteride and dutasteride. The class of drugs inhibit the 5-alpha reductase enzyme, significantly lowering the level of the primary male hormone in the prostate, dihydrotestosterone, without affecting the level of testosterone elsewhere in the body.

"Dr. Wilson's discovery set in motion a whole new era of treatment," Dr. McConnell said. "What we have shown in this trial is that while the alpha blocker (doxazosin) clearly contributes to symptom relief and a reduction in symptom worsening, use of finasteride to shrink the prostate and prevent further prostate growth is required to reduce the long-term complications of the disease, like the development of urinary retention or the need for invasive therapy."

The double-blind study followed 3,047 men with BPH over a four-and-a-half-year period. Study subjects were randomly given either doxazosin, finasteride, the combination therapy or a placebo. The combination of the two drugs "significantly delayed the clinical progression of BPH as compared with each drug individually among men with symptomatic BPH," the study concluded. In general, both drugs were well-tolerated by patients. Sexual function side effects occur in approximately 10 percent of men taking finasteride. Dizziness, low blood pressure, and fatigue can occur with alpha blockers like doxazosin.

"A 66 percent reduction in the risk of anything in medicine is pretty substantial," said Dr. Claus Roehrborn, UT Southwestern's chairman of urology and a trial investigator. "This is good news. The fly in the ointment is that two tablets cost more than one, so there is a cost factor."

In June, another study published in The New England Journal of Medicine demonstrated that the drug finasteride reduces the risk of prostate cancer by 25 percent.

BPH is a noncancerous enlargement of the prostate affecting more than half of all men over 60 in the United States. Symptoms can include frequent or urgent need to urinate, slowing of the urinary stream and hesitancy in urinating. With disease progression, some men can develop recurrent urinary tract infection and acute urinary retention. Surgery is still standard therapy for men who have developed complications of BPH.
The study was funded by the National Institute of Diabetes, Digestive and Kidney Diseases. Other participating medical centers included Yale University School of Medicine, the Mayo Medical School and Northwestern University Feinberg School of Medicine.

UT Southwestern Medical Center

Related Prostate Cancer Articles from Brightsurf:

Low risk of cancer spread on active surveillance for early prostate cancer
Men undergoing active surveillance for prostate cancer have very low rates - one percent or less - of cancer spread (metastases) or death from prostate cancer, according to a recent study published in the Journal of Urology®, an Official Journal of the American Urological Association (AUA).

ESMO 2020: Breast cancer drug set to transform prostate cancer treatment
A drug used to treat breast and ovarian cancer can extend the lives of some men with prostate cancer and should become a new standard treatment for the disease, concludes a major trial which is set to change clinical practice.

Major trial shows breast cancer drug can hit prostate cancer Achilles heel
A drug already licensed for the treatment of breast and ovarian cancers is more effective than targeted hormone therapy at keeping cancer in check in some men with advanced prostate cancer, a major clinical trial reports.

The Lancet: Prostate cancer study finds molecular imaging could transform management of patients with aggressive cancer
Results from a randomised controlled trial involving 300 prostate cancer patients find that a molecular imaging technique is more accurate than conventional medical imaging and recommends the scans be introduced into routine clinical practice.

Common genetic defect in prostate cancer inspires path to new anti-cancer drugs
Researchers found that, in prostate cancer, a mutation leading to the loss of one allele of a tumor suppressor gene known as PPP2R2A is enough to worsen a tumor caused by other mutations.

First prostate cancer therapy to target genes delays cancer progression
For the first time, prostate cancer has been treated based on the genetic makeup of the cancer, resulting in delayed disease progression, delayed time to pain progression, and potentially extending lives in patients with advanced, metastatic prostate cancer, reports a large phase 3 trial.

Men taking medications for enlarged prostate face delays in prostate cancer diagnosis
University of California San Diego School of Medicine researchers report that men treated with medications for benign prostatic hyperplasia (enlarged prostate) experienced a two-year delay in diagnosis of their prostate cancer and were twice as likely to have advanced disease upon diagnosis.

CNIO researchers confirm links between aggressive prostate cancer and hereditary breast cancer
The study has potential implications for families with members suffering from these types of tumours who are at an increased risk of developing cancer.

Distinguishing fatal prostate cancer from 'manageable' cancer now possible
Scientists at the University of York have found a way of distinguishing between fatal prostate cancer and manageable cancer, which could reduce unnecessary surgeries and radiotherapy.

Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.

Read More: Prostate Cancer News and Prostate Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to