Drug Protocols on Prostate Cancer Clinic Studies

Year 2021, Volume: 4 Issue: 9, 277 - 295, 22.12.2021

Mehmet Oğuz Şahin

Abstract

In this review article, used drug protocols on prostate cancer clinical studies. The review cover the possible treatment options include surgery, radiotherapy (RT), hormonal therapy, chemotherapy (CT), immunotherapy or a combination of these depending on the stage of the disease or the medical condition of the patient in prostate cancer cases.

Keywords

Prostate cancer, PCA, drug, protocol, case, anti carcinogen

References

• Abrahamsson PA. Potential benefits of intermittent androgen suppression therapy in the treatment of prostate cancer: a systematic review of the literature. Eur Urol 2010;57(1):49–59.
• Ahlgren G, Flodgren P, Tammela TL, Kellokumpu-Lehtinen P, Borre M, et al. A randomized phase III trial between adjuvant docetaxel and surveillance after radical prostatectomy for high risk prostate cancer: results of SPCG12. J Clin Oncol 2016; 34: abstr 5001.
• Bailar JC, Byar DP. Estrogen treatment for cancer of the prostate. Early results with 3 doses of diethylstilbestrol and placebo. Cancer 1970;26(2):257–261.
• Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al; PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014; 371(5): 424-433.
• Berry W, Dakhil S, Gregurich MA, Asmar L. Phase II trial of single-agent weekly docetaxel in hormone-refractory, symptomatic, metastatic carcinoma of the prostate. Semin Oncol 2001;28:8-15.
• Boccon-Gibod L, Fournier G, Bottet P, Marechal JM, Guiter J, Rischman P, Hubert J, Soret JY, Mangin P, Mallo C, Fraysse CE. Flutamide versus orchidectomy in the treatment of metastatic prostatecarcinoma.EurUrol. 1997;32(4):391-5; discussion 395-6.
• Bolla M, Collette L, Blank L, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 2002;360:103–8.
• Bolla M, Van Tienhoven G, Warde P, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 2010;11:1066–73.
• Boorjian SA, Karnes RJ, Viterbo R, et al. Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer. Cancer 2011;117:2883–91. Borgmann H, Lallous N, Ozistanbullu D, Beraldi E, Paul N, Dalal K, et al. Moving towards precision urologic oncology: targeting enzalutamide-resistant prostate cancer and mutated forms of the androgen receptor using the novel inhibitor darolutamide (ODM-201). Eur Urol 2018;73(1):4–8.
• Byar DP. Proceedings: the Veterans Administration Co-operative Urological Research Group studies of cancer of the prostate. Cancer 1973;32(5):1126–1130.
• Carles J, Gallardo E, Doménech M, et al. Phase 2 randomized study of radiation therapy and 3-year androgen deprivation with or without concurrent weekly docetaxel in high-risk localized pros-tate cancer patients. Int J Radiat Oncol Biol Phys 2019;103:344–52.
• Chandrasekar T, Yang JC, Gao AC, Evans CP. Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol. 2015 Jun; 4(3):365-380.
• Chang A, Yeap B, Davis T, Blum R, Hahn R, Khanna O, Fisher H, Rosenthal J, Witte R, Schinella R, Trump D.Double-blind, randomized study of primary hormonal treatment of stage D2 prostate carcinoma: flutamide versus diethylstilbestrol. J Clin Oncol. 1996 Aug;14(8):2250-7.
• Clegg NJ, Wongvipat J, Joseph JD, Tran C, Ouk S, Dilhas A, et al. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res 2012;72(6):1494–1503.
• Cooperberg MR, Cowan J, Broering JM, Carroll PR. High-risk pros-tate cancer in the United States, 1990–2007. World J Urol 2008;26:211–8.
• Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on Prostate Cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol 2017;71(4):630–642.
• Crawford ED, Eisenberger MA, McLeod DG, et al. A controlled trial of leuprolide with and withoud flutamide in prostatic carcinoma. N Eng J Med 1989: 321:419-424.
• Dalaere KPJ, Van Thillo EL. Flutamide monotherapy as primary treatment in advanced prostatic carcinoma: Semin Oncol 1991; 18: 13-18.
• Daskivich TJ, Oh WK. Recent progress in hormonal therapy for advanced prostate cancer. Curr Opin Urol. 2006 May;16(3):173-8.
• De Bono JS, Hardy-Bessard A, Kim C, Geczi L, Ford D, et al. Phase III non-inferiority study of cabazitaxel (C) 20 mg/m2 (C20) versus 25 mg/m2 (C25) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (D). J Clin Oncol 2016;34:abstr 5008.
• De Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010;376:1147-1154.
• De Coster R, Wouters W, Bruynseels J. P450-dependent enzymes as targets for prostate cancer therapy. J Steroid Biochem Mol Biol. 1996 Jan;56(1-6 Spec No):133-43.
• De Leval J, Boca P, Yousef E, Nicolas H, Jeukenne M, Seidel L, Bouffioux C, Coppens L, Bonnet P, Andrianne R, Wlatregny D. Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naive prostate cancer: results of a prospective randomized multicenter trial. Clin Prostate Cancer. 2002 Dec;1(3):163-171.
• Debruyne F, Bhat G, Garnick MB. Abarelix for injectable suspension: first-in-class gonadotropin-releasing hormone antagonist for prostate cancer. Future Oncol 2006;2(6):677–696.
• Denis LJ, Keuppens F, Smith PH, et al. Maximal androgen blockade: final analysis of EORTC phase III trial 30853. EORTC Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center. Eur Urol 1998;33(2):144-151.
• DeWys WD, Begg CB, Brodovsky H, Creech R, Khandekar J. A comparative clinical trial of adriamycin and 5-fluorouracil in advanced prostatic cancer: prognostic factors and response. Prostate 1983; 4: 1-11.
• Eisenberger MA, Abrams JS. Chemotherapy for prostatic carcinoma. Semin Urol 1988; 6: 303-310.
• Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ, Wilding G, Sears K, Culkin DJ, Thompson IM Jr, Bueschen AJ, Lowe BA. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med. 1998 Oct 8;339(15):1036-1042.
• Eisenberger MA, Simon R, O′Dwyer PJ, Wittes RE, Friedman MA. A reevaluation of nonhormonal cytotoxic chemotherapy in the treatment of prostatic carcinoma. J Clin Oncol 1985; 3: 827-841.
• Eser S, Zorlu F, Divtik RT, Cal C, Ozkan M, Kirkali Z. Incidence and epidemiological features of cancers of the genitourinary tract in Izmir between 1993-2002. Asian Pac J Cancer Prev. 2009;10(3):491-6.
• Ferris MJ, Liu Y, Ao J, et al. The addition of chemotherapy in the definitive management of high risk prostate cancer. Urol Oncol Semin Orig Investig 2018;36:475–87.
• Figg WD, Chau CH, Madan RA, Gulley JL, Gao R, et al. Phase II study of satraplatin and prednisone in patients with metastatic castration-resistant prostate cancer: a pharmacogenetic assessment of outcome and toxicity. Clin Genitourin Cancer 2013; 11: 229-237.
• Figg WD, Li H, Sissung T, Retter A, Wu S, et al. Pre-clinical and clinical evaluation of estramustine, docetaxel and thalidomide combination in androgen-independent prostate cancer. BJU Int 2007; 99: 1047-1055.
• Finianos,AragonChingJB.Zoledronic acid for the treatment of prostate cancer. Expert Opin Pharmacother. 2019;20(6):657-666.
• Fizazi K, Faivre L, Lesaunier F, Delva R, Gravis G, et al. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial. Lancet Oncol 2015; 16: 787-94.
• Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2019;380(13):1235-1246.
• Fourcade RO, Cariou G, Coloby P, Colombel P, Coulange C, Grise P, Mangin P, Soret JY, Poterre M. Total androgen blockade with Zoladex plus flutamide vs. Zoladex alone in advanced prostatic carcinoma: interim report of a multicenter, double-blind, placebo-controlled study. Eur Urol. 1990;18 Suppl 3:45-47.
• Fujita N, Koie T, Ohyama C, et al. Overall survival of high-risk prostate cancer patients who received neoadjuvant chemohormonal therapy followed by radical prostatectomy at a single institu-tion. Int J Clin Oncol 2017;22:1087–93.
• Gilbert DC, Duong T, Sydes M, Bara A, Clarke N, Abel P, James N, Langley R, Parmar M; STAMPEDE and PATCH Trial Management Groups. Transdermal oestradiol as a method of androgen suppression for prostate cancer within the STAMPEDE trial platform. BJU Int. 2018 May;121(5):680-683.
• Gravis G, Fizazi K, Joly F, Oudard S, Priou F, et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol 2013; 14: 149-158.
• Harris E. Immunotherapeutics for the treatment of prostate cancer: a patent landscape based on key therapeutic mechanisms of actions. Pharm Pat Anal 2018;7(1):47–57
• Hoskin P, Sartor O, O’Sullivan JM, Johannessen DC, Helle SI, Logue J. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double blind, phase 3 ALSYMPCA trial. Lancet Oncol. 2014;15(12):1397-1406.
• Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2018;378(26):2465-2474.
• Iversen P, McLeod DG, See WA, Morris T, Armstrong J, Wirth MP. Antiandrogen monotherapy in patients with localized or locally advanced prostate cancer: final results from the bicalutamide Early Prostate Cancer programme at a median follow-up of 9.7 years. BJU Int 2010;105:1074–81.
• James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 2016; 387: 1163-1177.
• Jordan Jr WP, Blackard CE, Byar DP. Reconsideration of orchiectomy in the treatment of advanced prostatic carcinoma. South Med J 1977;70(12):1411–1413.
• Kelly WK, Curley T, Slovin S, Heller G, McCaffrey J, et al. Paclitaxel, estramustine phosphate, and carboplatin in patients with advanced prostate cancer. J Clin Oncol 2001; 19: 44-53.
• Klotz L, Boccon-Gibod L, Shore ND, et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label,parallel-group phase III study in patients with prostate cancer. BJU Int 2008;102(11):1531–8.
• Kokontis JM, Liao S. Molecular action of androgen in the normal and neoplastic prostate. Vitam Horm 1999;55:219-307.
• Labrie F, Dupond A, Belanger A et al. Mew approach in the treatment of prostate cancer: complete insteat of partial withrawal of androgens. Prostate 1983;4:579-594.
• Ladoire S, Eymard JC, Zanetta S, Mignot G, Martin E, et al. Metronomic oral cyclophosphamide prednisolone chemotherapy is an effective treatment for metastatic hormone-refractory prostate cancer after docetaxel failure. Anticancer Res 2010; 30: 4317-4323.
• Lam JS, Leppert JT, Vemulapalli SN, Shvarts O, Belldegrun AS. Secondary hormonal therapy for advanced prostate cancer. J Urol. 2006 Jan;175(1):27-34.
• Lodde M, Lacombe L, Fradet Y. Salvage therapy with bicalutamide 150 mg in nonmetastatic castration-resistant prostate cancer. Urology 2010;76(5):1189–1193.
• McLeod DG. Hormonal therapy: historical perspective to future directions. Urology 2003;61(2 suppl 1):3–74.
• McLeod DG. Tolerability of Nonsteroidal Antiandrogens in the Treatment of Advanced Prostate Cancer. Oncologist 1997;2(1):18-27.
• Messing EM, Manola J, Sarosdy M, et al. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 1999;341(24):1781–1788.
• Millikan RE, Wen S, Pagliaro LC, Brown MA, Moomey B, et al. Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. J Clin Oncol 2008; 26: 5936-5942.
• Mita AC, Denis LJ, Rowinsky EK, Debono JS, Goetz AD, et al. Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-hour infusion every 3 weeks in patients with advanced solid tumors. Clin Cancer Res 2009;15:723-730.
• Moffat LE. Comparison of Zoladex, diethylstilbestrol and cyproterone acetate treatment in advanced prostate cancer. Eur Urol 1990;18 Suppl 3:26-7.
• Moilanen AM, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, et al. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signalingdirected prostate cancer therapies. Sci Rep 2015;5:12007.
• Morgan SC, Dearnaley DP. Additional therapy for high-risk prostate cancer treated with surgery: what is the evidence? Expert Rev Anticancer Ther 2009;9(7):939–951.
• Mottet N, Cornford P, van den Bergh RCN, Briers E, De Santis M, Fanti S, Gillessen S, Grummet J, Henry AM, Lam TB, Mason MD, van der Kwast TH, van der Poel HG, RouvièreO,SchootsIG,TilkiD,WiegelT.Guidelines Associates: van den Broeck T, Cumberbatch M, Fossati N, Gandaglia G, Grivas N, Lardas M, Liew M, Moris L, Oprea-Lager DE, Willemse PPM. Prostate Cancer. EAU Guidelines March 2019.
• Murphy GP, Priore RL, Scardino PT. Hormone-refractory metastatic prostatic cancer treated with methotrexate, cyclophosphamide plus adriamycin, cis-platinum plus 5-fluorouracil plus cyclophosphamide. National Prostatic Cancer Project randomized trial. Urology 1988; 32: 33-40.
• Nader R, El Amm J, Aragon-Ching JB. Role of chemotherapy in prostate cancer. Asian J Androl. 2018 May-Jun;20(3):221-229.
• Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fossa SD. et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213-223.
• Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr., Jones JA, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513-1520.
• Picus J, Schultz M. Docetaxel (Taxotere) as monotherapy in the treatment of hormone-refractory prostate cancer: preliminary results. Semin Oncol 1999;26: 14-18.
• Reis LO, Zani EL, García-Perdomo HA. Estrogen therapy in patients with prostate cancer: a contemporary systematic review. Int Urol Nephrol. 2018 Jun;50(6):993-1003.
• Rider JR, Sandin F, Andrén O, Wiklund P, Hugosson J, Stattin P. Long-term outcomes among noncuratively treated men according to prostate cancer risk category in a nationwide, population-based study. Eur Urol 2013;63:88–96.
• Rosenthal S, Hunt D, Sartor AO, et al. A phase III trial of 2 years of androgen suppression (AS) and radiation therapy (RT) with or without adjuvant chemotherapy (CT) for high-risk prostate can-cer: final results of Radiation Therapy Oncology Group (RTOG) phase III randomized trial NRG Oncology RTOG 9902. Int J Radiat Oncol Biol Phys 2015;93:294–302.
• Rosenthal SA, Hu C, Sartor O, et al. Effect of chemotherapy with docetaxel with androgen suppression and radiotherapy for local-ized high-risk prostate cancer: the randomized phase III NRG Oncology RTOG 0521 trial. J Clin Oncol 2019;37:1159–68.
• Ryan CJ, Smith MR, de Bono JS, et al; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138-148.
• Salata GC, Pinho CF, de Freitas ATAG, Aquino AM, Justulin LA, Mendes LO, Gonçalves BF, Delella FK, Scarano WR. Raloxifene decreases cell viability and migratory potential in prostate cancer cells (LNCaP) with GPR30/GPER1 involvement. J Pharm Pharmacol. 2019 Jul;71(7):1065-1071.
• Sanda MG, Cadeddu JA, Kirkby E, et al. Clinically localized prostate cancer: AUA/ASTRO/SUO Guideline. Part I: risk stratification, shared decision making, and care options. J Urol. 2018;199:683‐690.
• Sandler HM, Hu C, Rosenthal S, Sartor AO, Gomella LG, et al. A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521). J Clin Oncol 2015; 33: LBA5002.
• Schally AV, Kastin AJ, Arimura A. Hypothalamic follicle-stimulating hormone (FSH) and luteinizing hormone (LH) regulating hormone: structure, physiology, and clinical studies. Fertil Steril 1971;22(11):703–21.
• Schröder FH, Whelan P, de Reijke TM, Kurth KH, Pavone-Macaluso M, Mattelaer J, van Velthoven RF, Debois M, Collette L; Members of the EORTC Genito-Urinary Group. Metastatic prostate cancer treated by flutamide versus cyproterone acetate. Final analysis of the "European Organization for Research and Treatment of Cancer" (EORTC) Protocol 30892. Eur Urol. 2004 Apr;45(4):457-64.
• Schweizer MT, Zhou XC, Wang H, et al. The influence of prior abiraterone treatment on the clinical activity of docetaxel in men with metastatic castration-resistant prostate cancer. Eur Urol. 2014;66:646-652.
• Seidenfeld J, Samson DJ, Hasselblad V, et al. Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med 2000;132(7):566–77.
• Shaw MA, Nicholls PJ, Smith HJ. Aminoglutethimide and ketoconazole: historical perspectives and future prospects. J Steroid Biochem. 1988 Jul;31(1):137-46.
• Shenoy N, Kohli M. Role of systemic chemotherapy in metastatic hormone-sensitive prostate cancer. Indian J Urol 2016; 32: 257-261.
• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34.
• Smith M, Parker C, Saad F, Miller K, Tombal B, Ng QS, et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, doubleblind, placebo-controlled, phase 3 trial. The Lancet Oncology. 2019;20(3):408-419.
• Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.
• Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, et al. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. J Clin Oncol 2009; 27: 5431-5438.
• Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015; 373: 737-746. Tannock I, Gospodarowicz M, Meakin W, Panzarella T, Stewart L, 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: 590-597.
• Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351:1502-1512.
• Tilki D, Chen M-H, Wu J, et al. Surgery vs radiotherapy in the management of biopsy Gleason score 9-10 prostate cancer and the risk of mortality. JAMA Oncol 2018;1–9.
• Tombal B, Miller K, Boccon-Gibod L, et al. Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics. Eur Urol 2010;57(5):836–42. Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009; 324(5928):787-790.
• Trump DL, Loprinzi CL. Phase II trial of etoposide in advanced prostate cancer. Cancer Treat Rep 1984; 68: 1195-1196.
• Tyrrell CJ, Denis L, Newling D, et al. Casodex 10-200 mg daily, used as monotherapy for patients with advanced prostate cancer: an overview of the efficacy, tolerability and pharmacokinetics from three phase II doseranging studies. Casodex Study Group. Eur Urol 1998;33(1):39–53.
• Tyrrell CJ, Kaisary AV, Iversen P, et al. Randomised comparison of ‘Casodex’ (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol 1998;33(5):447–56.
• Van Soest RJ, van Royen ME, de Morre´ e ES, et al. Crossresistance between taxanes nd new hormonal agents abiraterone and enzalutamide may affect drug sequence choices in metastatic castrationresistant prostate cancer. Eur J Cancer. 2013; 49:3821-3830.
• Yagoda A, Petrylak D. Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer. Cancer 1993; 71: 1098-1109.
• Yamamoto S, Kawakami S, Yonese J, et al. Long-term oncological outcome in men with T3 prostate cancer: radical prostatectomy versus external-beam radiation therapy at a single institution. Int J Clin Oncol 2014;19:1085–91. Zhang BY, Li YF, Lai Y, Li YS, Chen ZJ. Effect of compound Chinese traditional medicine PC-SPES II in inhibiting proliferation of human prostate cancer cell LNCaP and on expressions of AR and PSA. Zhongguo Zhong Yao Za Zhi. 2015 Mar;40(5):950-6.