title: Toremifene, a selective estrogen receptor modulator, significantly improved biochemical recurrence in bone metastatic prostate cancer: a randomized controlled phase II a trial.
abstract: BACKGROUND
  Durability of androgen-deprivation therapy (ADT) for prostate cancer (PC) is limited. Additional selective estrogen receptor modulators (SERMs) may prolong the durability of ADT, because androgen and estrogen signaling drive PC progression.
  
  
  METHODS
  Men with treatment-naïve bone metastatic PC were randomly assigned in 1:1:1 fashion to receive ADT, toremifene 60 mg plus ADT (TOPADT), or raloxifene 60 mg plus ADT (RAPADT). The primary endpoint was the biochemical recurrence (BCR) rate, and secondary endpoints were changes of scores of the visual analogue scale (VAS) and the functional assessment of cancer therapy (FACT).
  
  
  RESULTS
  A total of 15 men, 5 each, were allocated to one of the three treatment arms. The basal serum prostate-specific antigen (PSA) level was 198 ng/mL (median, range; 30-8428). Bone metastases were graded as 1 (n = 11), 2 (n = 3), and 3 (n = 1) by the extent of disease. During the median follow-up period of 1370 days (range; 431-1983), BCR occurred in 3, 0 and 2 men in ADT, TOPADT and RAPADT group, respectively. The 5-year BCR-free rate was 30, 100 and 53 %, in ADT, TOPADT and RAPADT group, respectively (p = 0.04, ADT v.s. TOPADT, p = 0.48, ADT v.s. RAPADT and p = 0.12, TOPADT v.s. RAPADT). Scores of VAS improved in all groups and remained stable throughout the study. This analysis is limited as a preliminary result in a single center.
  
  
  CONCLUSIONS
  Toremifene with conventional ADT significantly improved the BCR rate in treatment-naïve bone metastatic PC. Further clinical trials are warranted to confirm the promising clinical efficacy of this combination therapy.
  
  
  BACKGROUND
  The protocol was registered at the University Hospital Medical Information Network ( UMIN ID;0,000,064,000 ) in Sep 25, 2011.
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. tfujimura-jua@umin.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Urology, Graduate School of Medicine, The Nihon University, Tokyo, Japan. takahashi.satoru@nihon-u.ac.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. kume@kuc.biglobe.ne.jp.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. turanotky@gmail.com.|Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. turanotky@gmail.com.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. knt56ta@hotmail.com.|Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. knt56ta@hotmail.com.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. yyamada2029@gmail.com.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. uromotofumi@gmail.com.
authors.forename: Motofumi
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. hifukuha@bk9.so-net.ne.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. tohru-tky@umin.ac.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. sinoue07@gmail.com.|Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. sinoue07@gmail.com.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. homma-uro@umin.ac.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017312:Toremifene / Q000008:administration & dosage*
chemical_list: D000726:Androgen Antagonists; D047628:Estrogen Receptor alpha; D017312:Toremifene; D017430:Prostate-Specific Antigen