The US Food and Drug Administration has
approved ALZA Corporations new drug application for a
once-yearly leuprolide acetate implant (Viadur) for the palliative
treatment of advanced prostate cancer. The implant is the first
product to provide continuous 12-month testosterone suppression with
a single treatment. It is also the first approved product to
incorporate ALZAs proprietary implant technology.
We are extremely pleased with the rapid clinical development of
Viadur, said Samuel R. Saks, MD, group vice president, ALZA
Pharmaceuticals. Viadur is a unique product that will provide
an important new therapeutic option to patients with advanced
Viadur is a drug-filled, miniature titanium cylinder that is placed
under the skin in the inner aspects of the patients upper arm
during an in-office surgical procedure. The product contains an
osmotic engine that continuously delivers precise levels of
leuprolide for 1 year, thus providing an alternative to frequent
Role of Testosterone Suppression Therapy
Testosterone suppression or hormonal therapy is commonly used for the
palliative treatment of advanced stages of prostate cancer, and
continuous testosterone suppression is usually required for many
months or years in this setting. Leuprolide is part of a class of
drugs known as luteinizing hormone-releasing hormone (LHRH) agonists
that work by decreasing the amount of testosterone produced by the body.
Leuprolide is well established as a palliative treatment for
advanced prostate cancer, and the once-yearly dosing regimen provided
by Viadur may present a convenient alternative for patients,
said James Gottesman, MD, clinical professor of Urology at the
University of Washington Medical School in Seattle. Currently,
therapeutic suppression of testosterone levels is primarily achieved
through intramuscular depot injections administered once every 1, 3,
or 4 months.
Demonstrated Efficacy and Safety
In two open-label, multicenter studies, 131 patients with advanced
prostate cancer were treated with Viadur and evaluated for up to 2
years. Following the initial surgical insertion of the implant, mean
serum testosterone concentrations decreased to therapeutically
desirable levels by week 4 in 99% of the patients in the study. Once
serum testosterone suppression was achieved, testosterone levels
remained suppressed for the duration of the 12-month treatment phase.
Following removal of the first implant, 118 patients had a new
implant inserted for a second year of therapy. No patient experienced
a clinically significant rise in serum testosterone upon removal of
the original implant and insertion of the new one.
Serum prostate-specific antigen (PSA) was monitored as a secondary
end point in the two clinical studies. Overall, after Viadur
treatment was started, concentrations of PSA decreased in the study population.
In clinical trials, the most common treatment-related side effects
were those expected with LHRH agonists, including vasodilation
(67.9%), asthenia (7.6%), gynecomastia (6.9%), depression (5.3%), and
sweating (5.3%). Local application site reactions reported by
patients after insertion or removal of the implant included bruising
(34.8%) and burning (5.6%). Local reactions developed in 10% of
patients the first 2 weeks after insertion, and the majority of those
reactions also resolved within the first 2 weeks. Reactions persisted
in 9.3% of patients.
Like other LHRH agonists, leuprolide causes a transient increase in
serum concentrations of testosterone during the first week of
treatment. Patients may experience worsening of symptoms or onset of
new symptoms, manifested by pain or bladder outlet obstruction.