Tomomi Kamba1, Toshiyuki Kamoto2, Shinichiro Maruo3, Takashi Kikuchi3, Yosuke Shimizu1, Shunichi Namiki4, Kiyohide Fujimoto5, Hiroaki Kawanishi6, Fuminori Sato7, Shintaro Narita8, Takefumi Satoh9, Hideo Saito10, Mikio Sugimoto11, Jun Teishima12, Naoya Masumori13, Shin Egawa14, Hideki Sakai15, Yusaku Okada16, Toshiro Terachi17, Osamu Ogawa18. 1. Department of Urology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. 2. Department of Urology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake-cho, Miyazaki, 889-1692, Japan. 3. Translational Research Informatics Center, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan. 4. Department of Urology, Osaki Citizen Hospital, 3-8-1 Furukawa-Honami, Osaki, 989-6183, Japan. 5. Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan. 6. Department of Urology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka, 543-8555, Japan. 7. Department of Urology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hazama-cho, Yufu, Oita, 879-5593, Japan. 8. Department of Urology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita, 010-8543, Japan. 9. Department of Urology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan. 10. Department of Urology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. 11. Department of Urology, School of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. 12. Department of Urology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. 13. Department of Urology, School of Medicine, Sapporo Medical University, S1 W16, Chuo-ku, Sapporo, 060-8543, Japan. 14. Department of Urology, School of Medicine, The Jikei University, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, 105-8461, Japan. 15. Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. 16. Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, 520-2192, Japan. 17. Department of Urology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara, 259-1193, Japan. 18. Department of Urology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. ogawao@kuhp.kyoto-u.ac.jp.
Abstract
OBJECTIVE: To examine the antitumor activity of zoledronic acid (ZA) combined with androgen deprivation therapy (ADT) for men with treatment-naive prostate cancer and bone metastasis. METHODS: We enrolled 227 men with treatment-naive prostate cancer and bone metastasis. Participants were randomly assigned (1:1 ratio) to receive combined androgen blockade alone (CAB group) or ZA with combined androgen blockade (CZ group). Time to treatment failure (TTTF), time to the first skeletal-related event (TTfSRE), and overall survival (OS) rates were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazards model. Median follow-up duration was 41.5 months. RESULTS:Median TTTFs were 12.4 and 9.7 months for the CZ and CAB groups, respectively (HR 0.75; 95 % CI 0.57-1.00; p = 0.051). For men with baseline prostate-specific antigen levels <200 ng/mL, median TTTFs were 23.7 and 9.8 months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.35-0.93; p = 0.023). Median TTfSREs were 64.7 and 45.9 months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.38-0.88; p = 0.009). OS was similar between the groups. CONCLUSIONS: This study failed to demonstrate that combined use of ZA and ADT significantly prolonged TTTF in men with treatment-naive prostate cancer and bone metastasis. However, it generates a new hypothesis that the combined therapy could delay the development of castration resistance in a subgroup of patients with low baseline prostate-specific antigen values <200 ng/mL. The treatment also significantly prolonged TTfSRE but did not affect OS.
RCT Entities:
OBJECTIVE: To examine the antitumor activity of zoledronic acid (ZA) combined with androgen deprivation therapy (ADT) for men with treatment-naive prostate cancer and bone metastasis. METHODS: We enrolled 227 men with treatment-naive prostate cancer and bone metastasis. Participants were randomly assigned (1:1 ratio) to receive combined androgen blockade alone (CAB group) or ZA with combined androgen blockade (CZ group). Time to treatment failure (TTTF), time to the first skeletal-related event (TTfSRE), and overall survival (OS) rates were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazards model. Median follow-up duration was 41.5 months. RESULTS: Median TTTFs were 12.4 and 9.7 months for the CZ and CAB groups, respectively (HR 0.75; 95 % CI 0.57-1.00; p = 0.051). For men with baseline prostate-specific antigen levels <200 ng/mL, median TTTFs were 23.7 and 9.8 months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.35-0.93; p = 0.023). Median TTfSREs were 64.7 and 45.9 months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.38-0.88; p = 0.009). OS was similar between the groups. CONCLUSIONS: This study failed to demonstrate that combined use of ZA and ADT significantly prolonged TTTF in men with treatment-naive prostate cancer and bone metastasis. However, it generates a new hypothesis that the combined therapy could delay the development of castration resistance in a subgroup of patients with low baseline prostate-specific antigen values <200 ng/mL. The treatment also significantly prolonged TTfSRE but did not affect OS.
Authors: T Kotake; M Usami; H Akaza; K Koiso; Y Homma; K Kawabe; Y Aso; S Orikasa; J Shimazaki; S Isaka; O Yoshida; Y Hirao; E Okajima; S Naito; J Kumazawa; H Kanetake; Y Saito; Y Ohi; Y Ohashi Journal: Jpn J Clin Oncol Date: 1999-11 Impact factor: 3.019
Authors: R Coleman; R de Boer; H Eidtmann; A Llombart; N Davidson; P Neven; G von Minckwitz; H P Sleeboom; J Forbes; C Barrios; A Frassoldati; I Campbell; O Paija; N Martin; A Modi; N Bundred Journal: Ann Oncol Date: 2012-10-09 Impact factor: 32.976
Authors: Robert Coleman; David Cameron; David Dodwell; Richard Bell; Caroline Wilson; Emma Rathbone; Maccon Keane; Miguel Gil; Roger Burkinshaw; Robert Grieve; Peter Barrett-Lee; Diana Ritchie; Victoria Liversedge; Samantha Hinsley; Helen Marshall Journal: Lancet Oncol Date: 2014-07-15 Impact factor: 41.316
Authors: M Dror Michaelson; Donald S Kaufman; Hang Lee; Francis J McGovern; Philip W Kantoff; Mary Anne Fallon; Joel S Finkelstein; Matthew R Smith Journal: J Clin Oncol Date: 2007-03-20 Impact factor: 44.544
Authors: M A Eisenberger; B A Blumenstein; E D Crawford; G Miller; D G McLeod; P J Loehrer; G Wilding; K Sears; D J Culkin; I M Thompson; A J Bueschen; B A Lowe Journal: N Engl J Med Date: 1998-10-08 Impact factor: 91.245
Authors: David P Dearnaley; Matthew R Sydes; Malcolm D Mason; Mark Stott; Christopher S Powell; Anne C R Robinson; Peter M Thompson; Leslie E Moffat; Sharon L Naylor; Mahesh K B Parmar Journal: J Natl Cancer Inst Date: 2003-09-03 Impact factor: 13.506
Authors: Claire L Vale; Sarah Burdett; Larysa H M Rydzewska; Laurence Albiges; Noel W Clarke; David Fisher; Karim Fizazi; Gwenaelle Gravis; Nicholas D James; Malcolm D Mason; Mahesh K B Parmar; Christopher J Sweeney; Matthew R Sydes; Bertrand Tombal; Jayne F Tierney Journal: Lancet Oncol Date: 2015-12-21 Impact factor: 41.316
Authors: Luke T Lavallée; Ryan McLarty; Christopher Tran; Rodney H Breau; Patrick Richard; Bobby Shayegan; Brita Danielson; Marie-Paul Jammal; Fred Saad Journal: Can Urol Assoc J Date: 2021-12 Impact factor: 1.862