臨床泌尿器科77巻2号

2023年02月発行

綜説

進行性前立腺癌に対する薬物療法の現状と展望

著者： 井上貴博¹

所属機関： ¹三重大学大学院医学系研究科腎泌尿器外科

ページ範囲：P.115 - P.121

要旨

　初診時に転移を認める進行性前立腺癌の治療は，LHRHアゴニスト/アンタゴニストまたは外科的去勢術が基本的な治療薬・方針であったが，その予後は必ずしも良好ではなく，多くは2年程度で難治性の去勢抵抗性前立腺癌に変異して，死に至る．この去勢抵抗性前立腺癌への変異メカニズムに基づいてさまざまな薬剤の開発が進み，その有用性が種々の臨床試験で証明されてきた．さらにはそうした薬剤を初期治療から投与することの有用性も示されている．大きく様変わりしてきている進行性前立腺癌の薬物療法を概説する．

参考文献

1） 国立がん研究センター : がん統計　https://ganjoho.jp （2022年12月1日閲覧）

2） Iguchi T, et al : Enzalutamide with Androgen Deprivation Therapy in Japanese men with Metastatic Hormone-Sensitive Prostate Cancer : A Subgroup Analysis of the Phase III ARCHES Study. Int J Urol 28 : 765-773, 2021

3） Nelson PS : Molecular States Underlying Androgen Receptor Activation : A Framework for Therapeutics Targeting Androgen Signaling in Prostate Cancer. J Clin Oncol 30 : 644-646, 2012

4） Gan L, et al : Inhibition of the Androgen Receptor as a Novel Mechanism of Taxol Chemotherapy in Prostate Cancer. Cancer Res 69 : 8386-8394, 2009

5） Zhu M-L, et al : Tubulin-Targeting Chemotherapy Impairs Androgen Receptor Activity in Prostate Cancer. Cancer Res 70 : 7992-8002, 2010

6） Tannock IF, et al : Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med 351 : 1502-1512, 2004

7） Petrylak DP, et al : Docetaxel and Estramustine Compared with Mitoxantrone and Prednisone for Advanced Refractory Prostate Cancer. N Engl J Med 351 : 1513-1520, 2004

8） de Bono JS, et al : Prednisone plus Cabazitaxel or Mitoxantrone for Metastatic Castration-Resistant Prostate Cancer Progressing After Docetaxel Treatment : A Randomised Open-Label Trial. Lancet 376 : 1147-1154, 2010

9） de Bono JS, et al : Abiraterone and Increased Survival in Metastatic Prostate Cancer. N Engl J Med 364 : 1995-2005, 2011

10） Ryan CJ, et al : Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy. N Engl J Med 368 : 138-148, 2013

11） Scher HI, et al : Increased Survival with Enzalutamide in Prostate Cancer After Chemotherapy. N Engl J Med 367 : 1187-1197, 2012

12） Beer TM, et al : Enzalutamide in Metastatic Prostate Cancer Before Chemotherapy. N Engl J Med 371 : 424-433, 2014

13） George DJ, et al : Treatment Patterns and Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer in a Real-world Clinical Practice Setting in the United States. Clin Genitourin Cancer 18 : 284-294, 2020

14） Gravis G, 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 14 : 149-158, 2013

15） Sweeney CJ, et al : Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med 373 : 737-746, 2015

16） Kyriakopoulos CE, et al : Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer : Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J Clin Oncol 36 : 1080-1087, 2018

17） Clegg NJ, et al : ARN-509 : A Novel Antiandrogen for Prostate Cancer Treatment. Cancer Res 72 : 1494-1503, 2012

18） Fizazi K, et al : Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 377 : 352-360, 2017

19） Fizazi K, et al : Abiraterone Acetate plus Prednisone in Patients with Newly Diagnosed High-Risk Metastatic Castration-Sensitive Prostate Cancer （LATITUDE） : Final Overall Survival Analysis of a Randomised, Double-Blind, Phase 3 Trial. Lancet Oncol 20 : 686-700, 2019

20） Davis ID, et al : Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med 381 : 121-131, 2019

21） Chi KN, et al : Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med 381 : 13-24, 2019

22） Chi KN, et al : Apalutamide in Patients with Metastatic Castration-Sensitive Prostate Cancer : Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol 39 : 2294-2303, 2021

23） Armstrong AJ, et al : ARCHES : A Randomized, Phase III Study of Androgen Deprivation Therapy with Enzalutamide or Placebo in Men with Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol 37 : 2974-2986, 2019

24） Uemura H, et al : Safety and Efficacy of Apalutamide in Japanese Patients with Metastatic Castration-Sensitive Prostate Cancer Receiving Androgen Deprivation Therapy : Final Report for the Japanese Subpopulation Analysis of the Randomized, Placebo-Controlled, Phase III TITAN Study. Int J Urol 29 : 533-540, 2022

25） Suzuki H, et al : Efficacy and Safety of Abiraterone Acetate plus Prednisone in Japanese Patients with Newly Diagnosed, Metastatic Hormone-Naive Prostate Cancer : Final Subgroup Analysis of LATITUDE, a Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study. Jpn J Clin Oncol 50 : 810-820, 2020

26） Fizazi K, et al : Abiraterone plus Prednisone Added to Androgen Deprivation Therapy and Docetaxel in de novo Metastatic Castration-Sensitive Prostate Cancer （PEACE-1） : A Multicentre, Open-Label, Randomised, Phase 3 Study with a 2 × 2 Factorial Design. Lancet 399 : 1695-1707, 2022

27） Parker CC, et al : Radiotherapy to the Primary Tumour for Newly Diagnosed, Metastatic Prostate Cancer （STAMPEDE） : A Randomised Controlled Phase 3 Trial. Lancet 392 : 2353-2366, 2018

28） Moilanen AM, et al : Discovery of ODM-201, a New-Generation Androgen Receptor Inhibitor Targeting Resistance Mechanisms to Androgen Signaling-Directed Prostate Cancer Therapies. Sci Rep 5 : 12007, 2015

29） Castro E, et al : PROREPAIR-B : A Prospective Cohort Study of the Impact of Germline DNA Repair Mutations on the Outcomes of Patients with Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol 37 : 490-503, 2019

30） Kimura H, et al : Prognostic Significance of Pathogenic Variants in BRCA1, BRCA2, ATM and PALB2 Genes in Men Undergoing Hormonal Therapy for Advanced Prostate Cancer. Br J Cancer 127 : 1680-1690, 2022

31） Abida W, et al : Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. JAMA Oncol 5 : 471-478, 2019

32） Wu YM, et al : Inactivation of CDK12 Delineates a Distinct Immunogenic Class of Advanced Prostate Cancer. Cell 173 : 1770-1782, 2018

33） Crabb SJ, et al : Overall Survival Update for Patients with Metastatic Castration-resistant Prostate Cancer Treated with Capivasertib and Docetaxel in the Phase 2 ProCAID Clinical Trial. Eur Urol 82 : 512-515, 2022

34） Mota JM, et al : Platinum-Based Chemotherapy in Metastatic Prostate Cancer with DNA Repair Gene Alterations. JCO Precis Oncol 4 : 355-366, 2020