Korean J Urol.  2011 Jul;52(7):461-465.

Efficacy of Alternative Antiandrogen Therapy for Prostate Cancer That Relapsed after Initial Maximum Androgen Blockade

• Choi JI
• Kim YB
• Yang SO
• Lee JK
• Jung TY

Abstract

PURPOSE
We evaluated the effectiveness of second-line maximum androgen blockade (MAB) with an alternative antiandrogen in patients who relapsed after initial MAB.
MATERIALS AND METHODS
We retrospectively analyzed 47 patients with prostate cancer who relapsed after initial MAB, including surgical or medical castration combined with antiandrogens, from January 1998 to December 2009. When the serum prostate-specific antigen (PSA) level was increased on three consecutive occasions, we discontinued the antiandrogen and then administered an alternative antiandrogen. Seven patients were assessed for antiandrogen withdrawal syndrome (AWS). The effect of the second-line MAB was evaluated by the serum PSA level, and response was subdivided into > or =50% and <50% PSA reductions from the baseline PSA at the start of second-line MAB.
RESULTS
PSA reduction was observed in 32 patients (68.1%). Among them, 23 (48.9%) achieved > or =50% PSA reductions with a mean response duration of 13.4+/-5.4 months. Nine (19.2%) patients reached <50% PSA reductions with a mean response duration of 12.2+/-6.2 months. The time to nadir PSA level after first-line MAB in the > or =50% PSA reduction group, <50% PSA reduction group, and PSA elevation group was 15.6+/-12.9 months, 11.8+/-6.0 months, and 8+/-6.5 months, respectively. That is to say, it was significantly longer in the responder groups (p=0.038).
CONCLUSIONS
Second-line MAB using an alternative antiandrogen is an effective treatment option before cytotoxic chemotherapy in patients who relapse after initial MAB.

Keyword

Androgen antagonists; Prostate-specific antigen; Prostatic neoplasms

MeSH Terms

Androgen Antagonists
Castration
Humans
Prostate
Prostate-Specific Antigen
Prostatic Neoplasms
Recurrence
Retrospective Studies
Androgen Antagonists
Prostate-Specific Antigen

Reference

1. Sharifi N, Dahut WL, Figg WD. Secondary hormonal therapy for prostate cancer: what lies on the horizon? BJU Int. 2008. 101:271–274.

2. Seruga B, Tannock IF. The changing face of hormonal therapy for prostate cancer. Ann Oncol. 2008. 19:Suppl 7. vii79–vii85.

3. Sharifi N, Gulley JL, Dahut WL. An update on androgen deprivation therapy for prostate cancer. Endocr Relat Cancer. 2010. 17:R305–R315.

4. Chodak GW. Maximum androgen blockade: a clinical Update. Rev Urol. 2005. 7:suppl 5. S13–S17.

5. Kim SJ, Kim SI. Current treatment strategies for castration-resistant prostate cancer. Korean J Urol. 2011. 52:157–165.

6. Mottet N, Bellmunt J, Bolla M, Joniau S, Mason M, Matveev V, et al. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2011. 59:572–583.

7. Van Allen EM, Ryan CJ. Novel secondary hormonal therapy in advanced prostate cancer: an update. Curr Opin Urol. 2009. 19:315–321.

8. Han KS, Cho KS, Lee SH, Hong SJ. Estramustine phosphate based chemotherapy for hormone refractory prostate cancer. Korean J Urol. 2007. 48:684–690.

9. Okegawa T, Nutahara K, Higashihara E. Alternative antiandrogen therapy in patients with castration-resistant prostate cancer: a single-center experience. Int J Urol. 2010. 17:950–955.

10. Lam JS, Leppert JT, Vemulapalli SN, Shvarts O, Belldegrun AS. Secondary hormonal therapy for advanced prostate cancer. J Urol. 2006. 175:27–34.

11. Suzuki H, Okihara K, Miyake H, Fujisawa M, Miyoshi S, Matsumoto T, et al. Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade. J Urol. 2008. 180:921–927.

12. Nishimura K, Arichi N, Tokugawa S, Yoshioka I, Kishikawa H, Ichikawa Y. Effects of flutamide as a second-line agent for maximum androgen blockade of hormone refractory prostate cancer. Int J Urol. 2007. 14:264–267.

13. Miyake H, Hara I, Eto H. Clinical outcome of maximum androgen blockade using flutamide as second-line hormonal therapy for hormone-refractory prostate cancer. BJU Int. 2005. 96:791–795.

14. Nakabayashi M, Regan MM, Lifsey D, Kantoff PW, Taplin ME, Sartor O, et al. Efficacy of nilutamide as secondary hormonal therapy in androgen-independent prostate cancer. BJU Int. 2005. 96:783–786.

15. Kojima S, Suzuki H, Akakura K, Shimbo M, Ichikawa T, Ito H. Alternative antiandrogens to treat prostate cancer relapse after initial hormone therapy. J Urol. 2004. 171:679–683.

16. Won YJ, Sung J, Jung KW, Kong HJ, Park S, Shin HR, et al. Nationwide cancer incidence in Korea, 2003-2005. Cancer Res Treat. 2009. 41:122–131.

17. Huggins C, Hodges CV. Studies on prostate cancer, I. the effect of castration, of estrogen and of androgen injection on serum phosphatase in metastatic carcinoma of the prostate. Cancer Res. 1941. 1:293–297.

18. Huggins C, Scott WW. Bilateral adrenalectomy in prostatic cancer; clinical features and urinary excretion of 17-ketosteroids and estrogen. Ann Surg. 1945. 122:1031–1041.

19. Schmitt B, Wilt TJ, Schellhammer PF, DeMasi V, Sartor O, Crawford ED, et al. Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: a systematic review. Urology. 2001. 57:727–732.

20. Moul JW. Twenty years of controversy surrounding combined androgen blockade for advanced prostate cancer. Cancer. 2009. 115:3376–3378.

21. Park SC, Choi HY, Kim CS, Hong SJ, Kim WJ, Lee SE, et al. Predictive variables of the progression to androgen independent prostate cancer after combined androgen blockade. Korean J Urol. 2007. 48:408–415.

22. Kelly WK, Scher HI. Prostate specific antigen decline after antiandrogen withdrawal: the flutamide withdrawal syndrome. J Urol. 1993. 149:607–609.

23. Sartor AO, Tangen CM, Hussain MH, Eisenberger MA, Parab M, Fontana JA, et al. Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426). Cancer. 2008. 112:2393–2400.

24. Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004. 351:1513–1520.

25. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004. 351:1502–1512.