Abstract
Corticosteroids have been used in the management of castration-resistant prostate cancer (CRPC) as a monotherapy or in combination with abiraterone acetate, docetaxel, or cabazitaxel. Several corticosteroids with varied potencies are used at different doses in daily medical practice. Although prednisolone or prednisone is the most commonly used corticosteroid in clinical trials, dexamethasone, coincident with its more intense glucocorticoid activity with less mineralocorticoid activity, has shown higher antitumor activity than prednisolone or prednisone without proven survival benefit.
In addition to the suppression of adrenal androgens, GR-mediated NF-κB inhibition is a potential mechanism of the action for dexamethasone in CRPC. Since long-term use of corticosteroids including dexamethasone is associated with multiple adverse events, a careful consideration of sequencing multiple therapies including corticosteroids is required. In this chapter, the biological antitumor activity, clinical benefits, and risks of corticosteroids in CRPC were discussed.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Tannock I, Gospodarowicz M, Meakin W, et al. Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol. 1989;7:590–7.
Reyes-Moreno C, Frenette G, Boulanger J, Lavergne E, Govindan MV, Koutsilieris M. Mediation of glucocorticoid receptor function by transforming growth factor beta I expression in human PC-3 prostate cancer cells. Prostate. 1995;26:260–9.
Nishimura K, Nonomura N, Satoh E, et al. Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer. J Natl Cancer Inst. 2001;93:1739–46.
Yano A, Fujii Y, Iwai A, Kageyama Y, Kihara K. Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells. Clin Cancer Res. 2006;12:3003–9.
Yano A, Fujii Y, Iwai A, Kawakami S, Kageyama Y, Kihara K. Glucocorticoids suppress tumor lymphangiogenesis of prostate cancer cells. Clin Cancer Res. 2006;12:6012–7.
Tuttle RM, Loop S, Jones RE, Meikle AW, Ostenson RC, Plymate SR. Effect of 5-alphareductase inhibition and dexamethasone administration on the growth characteristics and intratumor androgen levels of the human prostate cancer cell line PC-3. Prostate. 1994;24:229–36.
Weitzman AL, Shelton G, Zuech N, Owen CE, Judge T, Benson M, et al. Dexamethasone does not significantly contribute to the response rate of docetaxel and estramustine in androgen independent prostate cancer. J Urol. 2000;163:834–7.23.
Herrlich P. Cross-talk between glucocorticoid receptor and AP-1. Oncogene. 2001;20:2465–75.
De Bosscher K, Vanden Berghe W, Vermeulen L, Plaisance S, Boone E, Haegeman G. Glucocorticoids repress NF-kappaB-driven genes by disturbing the interaction of p65 with the basal transcription machinery, irrespective of coactivator levels in the cell. Proc Natl Acad Sci U S A. 2000;97:3919–24.
Yamamoto Y, Gaynor RB. Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer. J Clin Invest. 2001;107:135–42.
Chung TD, Yu JJ, Spiotto MT, Bartkowski M, Simons JW. Characterization of the role of IL-6 in the progression of prostate cancer. Prostate. 1999;38:199–207.
Okamoto M, Lee C, Oyasu R. Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro. Cancer Res. 1997;57:141–6.
Nishimura K, Nonomura N, Yasunaga Y, et al. Low doses of oral dexamethasone for hormone-refractory prostate carcinoma. Cancer. 2000;89:2570–6.
Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the cancer and leukemia group B 9182 study. J Clin Oncol. 1999;17:2506–13.
Tannock I, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormoneresistant prostate cancer: a Canadian randomized trial with palliative endpoints. J Clin Oncol. 1996;14:1756–64.
Small EJ, Vogelzang NJ. Second-line hormonal therapy for advanced prostate cancer: a shifting paradigm. J Clin Oncol. 1997;15:382–8.
Sartor O, Weinberger M, Moore A, Li A, Figg WD. Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer. Urology. 1998;52:252–6.
Kelly WK, Curley T, Leibretz C, Dnistrian A, Schwartz M, Scher HI. Prospective evaluation of hydrocortisone and suramin in patients with androgen-independent prostate cancer. J Clin Oncol. 1995;13(9):2208–13.
Storlie JA, Buckner JC, Wiseman GA, Burch PA, Hartmann LC, Richardson RL. Prostate specific antigen level and clinical response to low dose dexamethasone for hormonerefractory metastatic prostate carcinoma. Cancer. 1995;76:96–100.
Venkitaraman R, Thomas K, Huddart RA, Horwich A, Dearnaley DP, Parker CC. Efficacy of low-dose dexamethasone in castration-refractory prostate cancer. BJU Int. 2008;101(4):440–3.
Venkitaraman R, Lorente D, Murthy V, et al. A randomised phase 2 trial of dexamethasone versus prednisolone in castration-resistant prostate cancer. Eur Urol. 2015;67:673–9.
Morgan CJ, WK O, Naik G, Galsky MD, Sonpavde G. Impact of prednisone on toxicities and survival in metastatic castration-resistant prostate cancer: a systematic review and meta-analysis of randomized clinical trials. Crit Rev Oncol Hematol. 2014;90:253–61.
Scher HI, Fizazi K, Saad F, et al. Association of baseline corticosteroid with outcomes in a multivariate analysis of the phase 3 Affirm study of enzalutamide (ENZA),an androgen receptor signaling inhibitor (ARSI). European Society for Medical Oncology meeting, Vienna, Austria; September 28–October 2, 2012.
Montgomery B, Kheoh T, Molina A, Li J, Bellmunt J, Tran N, Loriot Y, Efstathiou E, Ryan CJ, Scher HI, de Bono JS. Impact of baseline corticosteroids on survival and steroid androgens in metastatic castration-resistant prostate cancer: exploratory analysis from COU-AA-301. Eur Urol. 2015;67(5):866–73.
Arora VK, Schenkein E, Murali R, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell. 2013;155:1309–22.
Sharifi N. Steroid receptors aplenty in prostate cancer. N Engl J Med. 2014;370:970–1.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Nishimura, K. (2018). Corticosteroid Therapy for CRPC. In: Arai, Y., Ogawa, O. (eds) Hormone Therapy and Castration Resistance of Prostate Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-10-7013-6_27
Download citation
DOI: https://doi.org/10.1007/978-981-10-7013-6_27
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-10-7012-9
Online ISBN: 978-981-10-7013-6
eBook Packages: MedicineMedicine (R0)