The purpose of this research is to determine the effect of timing of Zometa® administration
on bone mineral density of the lumbar spine and femoral neck in men undergoing androgen
deprivation therapy for prostate adenocarcinoma. In addition, the researchers will also
determine the effects of treatment with Zometa® on peripheral blood markers of bone
turnover, on peripheral blood gd T-cell frequencies and function, and to determine if the
above treatments elicit prostate antigen-specific IgG immune responses. The effects of the
above treatments on serial serum PSA measurements will also be examined.
Castration by GnRH agonist therapy with or without androgen antagonists has been a mainstay
for advanced prostate cancer. One of the most significant side effects of the use of
androgen ablative therapies has been a decrease in bone mineral density, potentially placing
patients at greater risk of osteoporosis and bone fractures. It is prudent to anticipate
this adverse effect of therapy and to minimize its severity with appropriate and timely
pharmacologic intervention. Zometa is a bisphosphonates and bisphosphonates are effective
inhibitors of osteoclastic bone resorption. Recent studies have shown that other
bisphosphonates were able to reduce the bone loss observed after 24 and 48 weeks of
treatment with a GnRH analogue. An unanswered question remains, however, in how frequently
these agents should be employed in clinical practice.
This is a three-arm randomized trial of Zometa® on bone mineral density in subjects with
stage D prostate cancer undergoing androgen ablation therapy. If subjects are enrolled in
Arm 1, the GnRH analogue would be administered every 3 months for 1 year. Four milligrams of
Zometa® would be administered IV over 15 minutes 7 days prior to beginning androgen
deprivation therapy. If subjects are enrolled in Arm 2, the GnRH analogue would be
administered every 3 months for one year, and 4 mg of Zometa® would be administered IV over
15 minutes at month 6. If subjects are enrolled in Arm 3, the GnRH analogue is administered
every 3 months for 1 year, with 4 mg of Zometa® administered IV over 15 minutes monthly for
6 months, beginning at month 6.
- Must have a histologic diagnosis of adenocarcinoma of the prostate.
- For patients without clinical metastasis treated by surgery, serum PSA values must be
> 0.2 ng/ml by two measurements at least two weeks apart. In patients treated with
ablative radiation therapy without clinical metastasis, three consecutive increases
in serum PSA must be documented, with at least a one-month interval between values
with the final PSA > 2ng/m as evidence of biochemical PSA failure. P
- Patients who have not had prior primary therapy such as radiation or surgery, are
required to have a detectable PSA of at least 0.2 ng/ml.
- Patients with evidence of metastatic disease are eligible irrespective of serum PSA
- Prior history of a second malignancy is allowed if treated with curative intent and
patient has been free of disease greater than five years
- ECOG performance status of < 2.
- Prior treatment with a GnRH analogue or anti-androgen.
- Evidence of immunosuppression or have been treated with immunosuppressive therapy,
such as chemotherapy, chronic treatment dose corticosteroids, or radiation therapy to
bones, within 6 months of study enrollment
- Current or treatment within 4 weeks with estrogen or estrogenic agents (including
herbal compound PC-SPES)
- Current or treatment within 4 weeks with herbal compounds for prostate cancer such as
PC-SPES or saw palmetto
- Current or treatment within 4 weeks with megestrol
- Current or prior treatment with a bisphosphonate, calcitonin, or other bone
- Current use of oral corticosteroids or any such use within the past 6 months
- Current use of potentially bone-toxic anticonvulsants (phenytoin, or carbamazepine)
- History of orchiectomy