|
The use of "Zometa" and "Pamidronate"
in prevention of osteoporosis and in retarding the progression of
metastases in bone. (November 2002)
Two major skeletal morbidities plague
men undergoing androgen deprivation therapy (ADT) for advanced prostate
cancer: osteoporosis and progression of bone metastasis. Both lead to pain
and fractures. In the October 2,2002, issue of the Journal of the National
Cancer Institute this issue was addressed in an editorial in concert with
a study of 643 men on ADT with metastatic bone lesions and rising PSA
values. The comparison was between treatment with 4 mg of Zometa at
three-week intervals versus placebo over 15 months.
Emerging data is clearly showing that osteoporosis is a significant
problem in association with androgen deprivation therapy. Multiple studies
show that after one year on ADT men show a 5% to 10% decrease in bone
mineral density (BMD) and ADT increases fracture risk 2-fold. 80% of men
with advanced prostate cancer develop skeletal metastasis and this group
is usually treated with ADT for some number of years.
Smith (N Eng J Med 345;948-955,2001) reported that Pamidronate at 60 mg IV
q 12 weeks (trade name "Aredia") (now succeeded by IV Zometa, 100-850
times more potent) protected men from any further loss in bone mineral
density at 48 weeks as compared to a loss of 8.5% in the placebo group.
It's interesting that 4 mg IV Zometa can prevent progression of
osteoporosis in cancer free individuals with dosing as infrequent as once
per year. The most efficient dosing schedule for Zometa in cancer patients
is under study.
Zometa (as do all bisphosphonates) interferes with bone resorbing action
of osteoclasts. Bone lesions in PC are classically considered "osteoblastic",
which implies that they are the result of bone build up as opposed to bone
loss ("osteolytic"). Clinicians might wonder if a drug that inhibits bone
resorption would be useful in a disease that is typically considered to be
associated with osteoblastic lesions. However, studies have shown that
there is a significant component of osteolysis in PC bone metastases.
The recent study of 643 men reported in the JNCI focused on men with
established skeletal metastasis. On average all men had 4.2 skeletal
metastases and median PSA was ~80 ng/mL. Zometa prolonged the time to the
development of new skeletal events to 420 days versus 321 for placebo
(P=.01) and markers of bone resorption were significantly decreased by
Zometa.
The accompanying editorial concluded that Zometa was a reasonable option
for men at high risk for bone fractures but more data would be required
before it becomes standard therapy for all PC men with any degree of
skeletal metastases. The issue of what extent of metastatic bone
involvement warrants intervention with Zometa is currently up to the
clinician's judgment.
The issue of cost is always relevant. 4 mg Zometa is priced at $915 and
infusion costs are additional. Perhaps further studies will refine the
recommendations regarding the usage of bisphosphonates relative to the
aspect of cost effectiveness.
Bottom Line: 1) Evaluate BMD in men undergoing ADT and utilize a
bisphosphonate to prevent bone loss, and 2) use Zometa in instances of
significant bone metastases.
«
Back to Article List
|
