Clinical endocrinological evaluation of the gonadal axis (testosterone, LH and FSH) in prostate cancer patients switched from a GnRH antagonist to a LHRH agonist

Basic and Clinical Andrology

Yoshiyuki Miyazawa¹  Haruo Kato¹  Seiji Arai¹  Yosuke Furuya¹  Yoshitaka Sekine¹  Masashi Nomura¹  Hidekazu Koike¹  Hiroshi Matsui¹  Yasuhiro Shibata¹  Kazuto Ito¹  Kazuhiro Suzuki¹ 

[1] Department of Urology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Gunma, 371-8511, Maebashi, Japan

关键词: Testosterone;    LHRH-agonist;    GnRH-antagonist;    Prostate cancer;   

Others  :  1218897
DOI  :  10.1186/s12610-015-0023-2

 received in 2015-03-10, accepted in 2015-06-03,  发布年份 2015

【 摘 要 】

Objectives

To investigate the levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prostate-specific antigen (PSA) in prostate cancer patients before and after the switch from degarelix to leuprolide treatments.

Methods

We enrolled 40 treatment-naïve prostate cancer patients who were treated initially with degarelix and were later switched to leuprolide. The subjects were divided into three groups depending on when they were switched to leuprolide: the 3-month group (3m; switched after 84 days, n=10), the 2-month group (2m; 56 days, n=10), and the 1-month group (1m; 28 days, n=20). Patient symptoms and hormone levels were measured after switching therapy. The castration level was defined as a serum testosterone level ≤50 ng/dl.

Results

Thirty-nine subjects (97.5%) achieved castration levels of testosterone (11±5.8 ng/dl) 2 weeks after degarelix was first administered, and the characteristics of these patients were investigated.Testosterone levels increased and exceeded the castration level in one subject each of the 3m (142 ng/dl), 2m (72 ng/dl), and 1m groups (63 ng/dl). All subjects achieved the castration level by day 5.In contrast to testosterone levels, the LH and FSH surge on day 2 was significantly higher in the 1m group than in the other groups. The clinical symptoms were not exacerbated before or after switching in any patients.

Conclusions

A testosterone surge was observed in 8.3 % of the study patients; however, it was very short-lived and mild. LH and FSH levels were significantly higher 1 month after administration compared with 2 or 3 months after degarelix administration.

【 授权许可】

   
2015 Miyazawa et al.

【 图 表 】

Fig. 1.

Fig. 2.

【 参考文献 】

• [1]Ito K. Prostate cancer in Asian man. Nat Rev Urol. 2014; 11:197-212.
• [2]Mohler JL, Kantoff PW, Armstrong AJ, Bahnson RR, Cohen M, D’Amico AV et al.. Prostate Cancer, version 2.2014. J Natl Compr Canc Netw. 2014; 12:686-718.
• [3]Garnick MB, Mottet N. New treatment paradigm for prostate cancer: abarelix initiation therapy for immediate testosterone suppression followed by a luteinizing hormone-releasing hormone agonist. BJU Int. 2012; 110:499-504.
• [4]Zuckermann JM, Eure G, Malcolm J, Currie L, Given R. Prospective evaluation of testosterone fluctuations during a transition of therapy from degarelix to leuprolide in patients on androgen deprivation therapy. Urology. 2014; 83:670-4.
• [5]Groenestege WM, Bui HN, Kate JT, Menheere P, Oosterhuis WP, Vader HL et al.. Accuracy of first and second generation testosterone assays and improvement through sample extraction. Clin Chem. 2012; 58:1154-6.
• [6]Huggins C, Hodges CV. Studies on prostatic cancer; the effect of castration, of estrogen and of androgen injection on serum phosphates in metastatic carcinoma of the prostate. Cancer Res. 1941; 1:293-7.
• [7]Leuprolide versus diethylstilbestrol for metastatic prostate cancer. N Engl J Med. 1984; 311:1281-6.
• [8]Faure N, Lemay A, Laroche B, Robert G, Plante R, Jean C et al.. Preliminary results on the clinical efficacy and safety of androgen inhibition by an LHRH agonist alone or combined with an antiandrogen in the treatment of prostatic carcinoma. Prostate. 1983; 4:601-24.
• [9]Thompson IM, Zeidman EJ, Rodriguez FR. Sudden death due to disease flare with luteinizing hormone-releasing hormone agonist therapy for carcinoma of the prostate. J Urol. 1990; 144:1479-80.
• [10]Kuhn JM, Billebaud T, Navratil H, Moulonquet A, Fiet J, Grise P et al.. Prevention of the transient adverse effects of a gonadotropin-releasing hormone analogue (buserelin) in metastatic prostatic carcinoma by administration of an antiandrogen (nilutamide). N Engl J Med. 1989; 321:413-8.
• [11]Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA et al.. A controlled trial of luprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989; 321:419-24.
• [12]Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL et al.. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analog therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX combination study group. Cancer. 1996; 78:2164-9.
• [13]Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P et al.. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, pararell-group phase III study in patients with prostate cancer. BJU Int. 2008; 102:1531-8.
• [14]Crawford ED, Tombal B, Miller K, Boccon-Gibod L, Schröder F, Shore N et al.. A phase III extension trial with a 1-arm crossover from leuprolide to degarelix: comparison of gonadotropin-releasing hormone agonist and antagonist effect on prostate cancer. J Urol. 2011; 186:889-97.
• [15]Fujimoto H, Nakanishi H, Miki T, Kubota Y, Takahashi S, Suzuki K et al.. Oncological outcomes in 2004: report from the Cancer Registration Committee of the JUA. Int J Urol. 2011; 18:876-81.
• [16]Hinotsu S, Akaza H, Usami M, Ogawa O, Kagawa S, Kitamura T et al.. Current status of endocrine therapy for prostate cancer in Japan-analysis of primary androgen deprivation therapy on the basis of data collected by J-cap. Jpn J Clin Oncol. 2007; 37:775-81.