Androgen blockade has potential applications beyond late-stage metastatic
cancer of the prostate, according to Nelson N. Stone, md, Professor of
Urology and Radiation Oncology at Mt. Sinai School of Medicine. Although
androgen withdrawal therapy (AWT) has been used effectively to prolong
survival in patients with metastatic disease, its use in the neoadjuvant
and adjuvant setting prior to surgery and radiation therapy (RT) represents
a promising new area of investigation, Dr. Stone said at the 14th Symposium
of the Chemotherapy Foundation.
Dr. Stone cited a recent study that showed no significant difference
in outcome between patients treated with radical prostatectomy and radiation.
Thanks to prostate-specific antigen (PSA) testing following definitive
therapy, he added, it is now possible to identify the high number of patients
who fail local therapy.
"Upwards of 35% to 50% of men treated for cure will be found to
have a rising PSA within 5 years of treatment," Dr. Stone continued.
For those patients, intermittent androgen withdrawal may result in a longer
time to progression. Initial phase II studies of post-treatment intermittent
AWT have been promising, and larger clinical trials are being planned.
Complete hormone therapy (CHT) has virtually replaced orchiectomy with
or without oral estrogens. Combining the luteinizing hormone-releasing
hormone (LHRH) agonist leuprolide (Lupron) with an oral antiandrogen, such
as flutamide (Eulexin) or the newer agent, biclutamide (Casodex), confers
a 25% to 35% survival advantage over orchiectomy or leuprolide alone.
"Nonetheless," Dr. Stone said, "perhaps we can do better
with the use of adjuvant hormonal therapy in conjunction with radiation
or surgery." He described the use of AWT before radical prostatectomy
or RT as exciting. According to Dr. Stone, 3 months of CHT prior to surgery
will shrink the tumor enough to result in a sixfold decrease in the likelihood
of encountering a positive surgical margin. "It remains to be seen
whether this will translate into improved survival," he said.
A recent Radiation Therapy Oncology Group study reported a 36% progression-free
survival when 4 months of CHT preceded radiation, compared to 14% with
With RT, the issues are different, Dr. Stone explained. Four months
of CHT will decrease the size of the prostate by about 40%. It has been
established that radiation works best when the tumor volume is minimal.
It, in fact, allows the radiation dose to be minimized to contiguous structures.
Furthermore, there may be a synergistic effect on apoptosis when CHT
precedes radiation. A smaller prostate also has benefits for brachytherapy
and makes imaging easier, he added.
Prostate cancer rates are expected to peak in the year 2000, Dr. Stone
said making improved treatment strategies essential. Investigation of broader
applications of AWT may well point the way, he concluded.