Dutasteride Followed By Watchful Waiting May Delay Cancer Progression in Men With Early Prostate Cancer

Dutasteride (Avodart)—a drug commonly used to treat benign prostatic hyperplasia—may also be useful as part of a “watchful waiting” strategy (ie, active surveillance) to delay the progression of prostate cancer in men with early prostate cancer. According to a randomized, placebo-controlled trial of men with early prostate cancer followed by watchful waiting, dutasteride delayed the time to prostate cancer progression, increased the percentage of men with no detectable prostate cancer on repeat biopsy, and lessened anxiety related to prostate cancer. The study, which was supported by GlaxoSmithKline, was presented at the 2011 ASCO Genitourinary Cancers Symposium.

Investigators with the REDEEM (Reduction by Dutasteride of Clinical Progression Events in Expectant Management) study are hopeful that the use of dutasteride in men with low-risk, early-stage prostate cancer can reduce the use of more aggressive therapy following watchful waiting.

“In some cases, we treat prostate cancer that may never become life-threatening,” said Neil Fleshner, MD, the lead author of the study. “I’m hoping that these results, showing that men may be able to take a drug that slows the cancer’s growth, may allow more men to pursue active surveillance for even longer periods of time.”

Fleshner is head of the Division of Urology at University Health Network in Toronto, Ontario, Canada, and is the Love Chair in Prostate Cancer Prevention at the Princess Margaret Hospital in Toronto. Fleshner acknowledged that this was an off-label use of dutasteride, but in his view, men with early low-risk prostate cancer should consider use of this drug along with active surveillance.

The REDEEM study randomized 302 men aged 48 to 82 years with early-stage localized prostate cancer to treatment with dutasteride or placebo for 3 years.

Early-stage localized prostate cancer was defined as prostatespecific antigen (PSA) levels <11 ng/mL and Gleason score of ≤6 (ie, <3 cores of a biopsy positive), and <50% of any core positive. Repeat 12-core biopsies were performed at 18 and 36 months or at any time during the study for indications of disease progression. The primary endpoint of the study was time to progression, defined as the earliest of either pathologic progression on Gleason score, or core biopsy, or decision to have active treatment for prostate cancer (ie, radical prostatectomy, radiation therapy, or hormonal ablation therapy).

Ninety-six percent of those enrolled in the trial achieved the primary endpoint or had a post-baseline biopsy. Dutasteride reduced time to cancer progression by 38.9% relative to placebo (P = .007). Prostate cancer progression occurred in 54 patients (38%) in the dutasteride group versus 71 (49%) of the placebo group. Men in the dutasteride group also had less chance of prostate cancer detected at the final biopsy: 50 (36%) of the dutasteride group versus 31 (23%) of the placebo group had no cancer detected in the final biopsy.

Fleshner explained that men with early prostate cancer followed by watchful waiting frequently have some anxiety associated with monitoring and no treatment, even though they are aware that many cases of early prostate cancer will not require further treatment for disease progression. Using the Memorial Anxiety Scale for Prostate Cancer, a standardized test for anxiety in patients with prostate cancer, anxiety related to prostate cancer was significantly reduced by dutasteride compared with placebo (P = .036). Drug-related adverse events related to dutasteride were similar to those reported previously.

“This is an important paper,” said Nicholas J. Vogelzang, MD, chair and medical director of the Developmental Therapeutics Committee of US Oncology. Vogelzang moderated a presscast at the symposium in which the study results were presented. “Men feel increased anxiety on watchful waiting, and with this drug PSA drops about 50% and the size of the prostate gland is reduced,” Vogelzang said. “Thus, men are getting treatment and they are getting reduced symptoms. This study teaches us that dutasteride seems to reduce the amount of cancer in the prostate. This is a step forward.”