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.
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.
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.
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.
International journal of clinical oncology. 2016 Sep 10 [Epub]
Tomomi Kamba, Toshiyuki Kamoto, Shinichiro Maruo, Takashi Kikuchi, Yosuke Shimizu, Shunichi Namiki, Kiyohide Fujimoto, Hiroaki Kawanishi, Fuminori Sato, Shintaro Narita, Takefumi Satoh, Hideo Saito, Mikio Sugimoto, Jun Teishima, Naoya Masumori, Shin Egawa, Hideki Sakai, Yusaku Okada, Toshiro Terachi, Osamu Ogawa, ZAPCA Study Group
Department of Urology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan., Department of Urology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake-cho, Miyazaki, 889-1692, Japan., Translational Research Informatics Center, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan., Department of Urology, Osaki Citizen Hospital, 3-8-1 Furukawa-Honami, Osaki, 989-6183, Japan., Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan., Department of Urology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka, 543-8555, Japan., Department of Urology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hazama-cho, Yufu, Oita, 879-5593, Japan., Department of Urology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita, 010-8543, Japan., Department of Urology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan., Department of Urology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan., Department of Urology, School of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan., Department of Urology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan., Department of Urology, School of Medicine, Sapporo Medical University, S1 W16, Chuo-ku, Sapporo, 060-8543, Japan., Department of Urology, School of Medicine, The Jikei University, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, 105-8461, Japan., Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan., Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, 520-2192, Japan., Department of Urology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara, 259-1193, Japan., Department of Urology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. .