Defining the role of antiandrogens in the treatment of prostate cancer.
OBJECTIVE
Although antiandrogens have been used as monotherapy and in combination with other treatment modalities for management of metastatic prostate cancer, their major role to date has been one in which they are used in conjunction with surgical or medical castration for treatment of Stage D (T4/Nx/M1) carcinoma of the prostate. The widespread use of prostate-specific antigen (PSA) is increasing the number of men who are diagnosed with earlier stages of this disease, thus resulting in a greater number of definitive therapeutic procedures. Also, PSA has become the primary modality for following these patients after definitive treatment. Because the use of PSA results in the discovery of lower volume of disease and in discerning earlier recurrence of disease, the question arises as to whether an antiandrogen alone could be an adequate treatment in both neoadjuvant and adjuvant settings.


METHODS
As data accumulate that point to the efficacy of combined androgen blockade in metastatic disease, a protocol has been developed to test the hypothesis of intermittent combined treatment in patients who present with minimal disease and good performance status. In this study, the antiandrogen bicalutamide will be used in combination with the luteinizing hormone-releasing hormone (LHRH) analogue goserelin acetate. Also, short-term combined androgen ablation continues to be investigated prior to both radiation therapy and radical prostatectomy for localized disease.


RESULTS
Two groups of patients are ideal candidates for the use of antiandrogen monotherapy following radical prostatectomy: those whose PSA values do not fall to undetectable levels and the far larger group of men who have capsular penetration or positive surgical margins with nondetectable PSA levels. Protocols have been developed to assess the clinical potential of bicalutamide as the sole adjuvant therapy in these postprostatectomy patients, based in no small part on the relative paucity of side effects of this antiandrogen.


CONCLUSIONS
Antiandrogens in general, and bicalutamide in particular, are poised to play an increasing role in the treatment of all stages of adenocarcinoma of the prostate. The safety profile of bicalutamide, combined with its long half-life, resulting in once-a-day dosing, makes it an ideal choice for clinical trials evaluating an antiandrogen, either alone or combined with reversible medical castration, in earlier stages of prostate cancer as well as in various combination regimens in metastatic disease.
McLeod
D G
DG
Walter Reed Army Medical Center, Urology Service, Washington, DC 20307-5001, USA.
Kolvenbag
G J
GJ
D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000726:Androgen Antagonists