Efficacy and Safety of Nilutamide in Patients with Metastatic Prostate Cancer who Underwent Orchiectomy: A Systematic Review and Metaanalysis

Author(s): Muhammed Rashid, K. Shamshavali, Manik Chhabra*.

Journal Name: Current Clinical Pharmacology

Volume 14 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Prostate cancer is the sixth leading cause of death, among all cancer deaths By 2030, this burden is expected to increase with 1.7 million new cases and 499,000 new deaths. We aimed to evaluate the efficacy and safety of Nilutamide in metastatic prostate cancer (mPCa) patients who underwent orchiectomy.

Methods: A comprehensive search was conducted in the Medline/PubMed and Cochrane Library. References from included studies and studies from clinicaltrials.gov were explored without language and date restrictions. We included only randomized controlled trials, comparing the safety and efficacy of Nilutamide in Metastatic Prostate Cancer (mPCa) patients who underwent orchiectomy with placebo. The outcomes of concerns were survival and the response of drug and safety.. Quality of the included studies was assessed using the Cochrane Risk of Bias Tool. Two authors were independently involved in the study selection, data extraction and quality assessment. Disagreements between the two reviewers were resolved by consulting a third reviewer.

Results: A total of five out of 244 studies were included in meta-analysis involving1637 participants. Nilutamide group showed improved response rate (RR=1.77, 95%CI 1.46-2.14, p<0.00001), disease progression (RR=0.59, 95%CI 0.47-0.73, p<0.00001), complete response (RR=2.13, 95%CI 1.40-3.23, p=0.003) and clinical benefit (RR=1.23, 95%CI 1.13-1.34, p<0.00001) when compared to placebo; however, stable disease favored the control group (RR=0.80, 95%CI 0.68-0.94, p=0.007). In addition, patients on Nilutamide showed prolonged progression-free survival and overall survival. Nausea and vomiting were the most common adverse events reported in Nilutamide group.

Conclusion: Evidence suggests that patients with mPCa who underwent orchiectomy receiving Nilutamide showed significant improvement in progression-free survival and overall survival response rate and clinical benefits in comparison with the placebo group.

Keywords: Nilutamide, metastatic prostate cancer, anti-androgen, orchiectomy, safety, efficacy.

[1]
Jain S, Saxena S, Kumar A. Epidemiology of prostate cancer in India. Meta Gene 2014; 2: 596-605.
[http://dx.doi.org/10.1016/j.mgene.2014.07.007] [PMID: 25606442]
[2]
Park JC, Eisenberger MA. Advances in the treatment of meta-static prostate cancer. Proceedings of the InMayo Clinic. 2015 Dec 31; Elsevier 2015; pp. 1719-33.
[3]
Yoo S, Choi SY, You D, Kim CS. New drugs in prostate cancer. Prostate Int 2016; 4(2): 37-42.
[http://dx.doi.org/10.1016/j.prnil.2016.05.001] [PMID: 27358841]
[4]
Ricci F, Buzzatti G, Rubagotti A, Boccardo F. Safety of antiandrogen therapy for treating prostate cancer. Expert Opin Drug Saf 2014; 13(11): 1483-99.
[http://dx.doi.org/10.1517/14740338.2014.966686] [PMID: 25270521]
[5]
Kassouf W, Tanguay S, Aprikian AG. Nilutamide as second line hormone therapy for prostate cancer after androgen ablation fails. J Urol 2003; 169(5): 1742-4.
[http://dx.doi.org/10.1097/01.ju.0000057795.97626.66] [PMID: 12686822]
[6]
Velázquez-Macías RF, Aguilar-Patiño S, Cortez-Betancourt R, Rojas-Esquivel I, Fonseca-Reyes G, Contreras-González N. Evaluation of efficacy of buserelin plus Nilutamide in Mexi-can Male patients with advanced prostate cancer. Rev Mex Urol 2016; 76: 346-51.
[7]
Dijkman GA, Janknegt RA, De Reijke TM, Debruyne FM. Long-term efficacy and safety of nilutamide plus castration in advanced prostate cancer, and the significance of early prostate specific antigen normalization. J Urol 1997; 158(1): 160-3.
[http://dx.doi.org/10.1097/00005392-199707000-00051] [PMID: 9186345]
[8]
Group PC. Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Prostate Cancer Trialists’ Collaborative Group. Lancet 2000; 355(9214): 1491-8.
[http://dx.doi.org/10.1016/S0140-6736(00)02163-2] [PMID: 10801170]
[9]
Béland G, Elhilali M, Fradet Y, et al. A controlled trial of castration with and without nilutamide in metastatic prostatic carcinoma. Cancer 1990; 66(5)(Suppl.): 1074-9.
[http://dx.doi.org/10.1002/cncr.1990.66.s5.1074] [PMID: 2203517]
[10]
Beland G. Combination of Anandron with orchiectomy in treatment of metastatic prostate cancer. Results of a double-blind study. Urology 1991; 37(2)(Suppl.): 25-9.
[http://dx.doi.org/10.1016/0090-4295(91)80098-R] [PMID: 1992600]
[11]
Janknegt RA. Total androgen blockade with the use of orchiectomy and nilutamide (Anandron) or placebo as treatment of metastatic prostate cancer. Cancer 1993; 72(12)(Suppl.): 3874-7.
[http://dx.doi.org/10.1002/1097-0142(19931215)72:12+<3874:AID-CNCR2820721722>3.0.CO;2-#] [PMID: 8252507]
[12]
Janknegt RA, Abbou CC, Bartoletti R, et al. Orchiectomy and nilutamide or placebo as treatment of metastatic prostatic cancer in a multinational double-blind randomized trial. J Urol 1993; 149(1): 77-82.
[http://dx.doi.org/10.1016/S0022-5347(17)36003-2] [PMID: 7678043]
[13]
Namer M, Toubol J, Caty A, et al. A randomized double-blind study evaluating Anandron associated with orchiectomy in stage D prostate cancer. J Steroid Biochem Mol Biol 1990; 37(6): 909-15.
[http://dx.doi.org/10.1016/0960-0760(90)90442-N] [PMID: 2285605]
[14]
Wallis CJD, Klaassen Z, Bhindi B, et al. Comparison of abiraterone acetate and docet-axel with androgen deprivation therapy in high-risk and meta-static hormone-naïve prostate cancer: a systematic review and network meta-analysis. Eur Urol 2018; 73(6): 834-44.
[http://dx.doi.org/10.1016/j.eururo.2017.10.002] [PMID: 29037513]
[15]
Botrel TE, Clark O, dos Reis RB, et al. Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis. BMC Urol 2014; 14: 9.
[http://dx.doi.org/10.1186/1471-2490-14-9] [PMID: 24460605]
[16]
Samson DJ, Seidenfeld J, Schmitt B, et al. Systematic review and meta-analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma. Cancer 2002; 95(2): 361-76.
[http://dx.doi.org/10.1002/cncr.10647] [PMID: 12124837]
[17]
Bertagna C, De Géry A, Hucher M, François JP, Zanirato J. Efficacy of the combination of nilutamide plus orchidectomy in patients with metastatic prostatic cancer. A meta-analysis of seven randomized double-blind trials (1056 patients). Br J Urol 1994; 73(4): 396-402.
[http://dx.doi.org/10.1111/j.1464-410X.1994.tb07603.x] [PMID: 8199827]
[18]
Kunath F, Grobe HR, Ruecker G, et al. Non‐steroidal anti-androgen monotherapy compared with luteinising hormone–releasing hormone agonists or surgical castration monotherapy for ad-vanced prostate cancer. Cochrane Libr 2014.
[19]
Akaza H, Yamaguchi A, Matsuda T, et al. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol 2004; 34(1): 20-8.
[http://dx.doi.org/10.1093/jjco/hyh001] [PMID: 15020659]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 14
ISSUE: 2
Year: 2019
Page: [108 - 115]
Pages: 8
DOI: 10.2174/1574884714666190112151202

Article Metrics

PDF: 17
HTML: 2