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(Drug information on estrogens). Combining the luteinizing hormone-releasing hormone (LHRH) agonist leuprolide (Lupron) with an oral antiandrogen, such as flutamide(Drug information on 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 radiation alone.
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.