title: Effective and Safe Administration of Low-Dose Estramustine Phosphate for Castration-Resistant Prostate Cancer.
abstract: Despite the favorable toxicity profile at the standard dose of 560 mg daily, the tolerability and toxicology of estramustine phosphate (EMP) have been a cause for concern at administration. Moreover, we do not know whether a lower dose of 280 mg of EMP daily can be administered with some efficacy and fewer side effects. The results of our phase II study suggest that low-dose EMP is a safe treatment option with the same efficacy in patients with castration-resistant prostate cancer.
  
  
  BACKGROUND
  We evaluated the efficacy and safety of low-dose estramustine phosphate (EMP) in Japanese patients with castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  The present study was a single-arm, nonrandomized prospective study in which all patients received EMP orally twice daily for a total dose of 280 mg/day. A total of 31 patients with CRPC were enrolled from December 2009 to December 2012 at 5 institutions in Japan. The primary endpoint was the prostate-specific antigen (PSA) response, defined as a 50% decline in the serum PSA level, confirmed ≥ 3 weeks later. The secondary endpoints included the objective response rate, interval to PSA progression, PSA response duration, progression-free survival, disease-specific survival, overall survival, safety, and quality-of-life assessment using the Functional Assessment of Cancer Therapy-Prostate scores.
  
  
  RESULTS
  Ten patients (32%) had a PSA response, and no patient had an objective response. The treatment was well tolerated, and the most frequent toxicities were grade 1 to 2 nausea/vomiting, anorexia, and gynecomastia. The median interval to PSA progression was 140 days (95% confidence interval [CI], 117-260 days). The PSA response duration was 119 days (95% CI, 49-219 days). The median progression-free survival was 213 days (95% CI, 167-422 days). The 3-year disease-specific survival and overall survival rates were 68.6% (median not reached; 95% CI, 33 months to not available) and 59.9% (median 42 months, 95% CI, 28 months to not available), respectively.
  
  
  CONCLUSIONS
  Low-dose EMP seems to be a safe treatment option with some efficacy in patients with CRPC.
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Urology, Japanese Red Cross Otsu Hospital, Otsu, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Ogura
authors.affiliation: Department of Urology, Kobe City Medical Center General Hospital, Kobe, Japan.
authors.forename: Mutushi
authors.initials: M
authors.lastname: Kawakita
authors.affiliation: Department of Urology, Miyazaki University Faculty of Medicine, Miyazaki, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tsukino
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Akamatsu
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Toshinari
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Department of Urology, Kyoto City Hospital, Kyoto, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Segawa
authors.affiliation: Department of Urology, Kobe City Medical Center General Hospital, Kobe, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Sugino
authors.affiliation: Department of Urology, Miyazaki University Faculty of Medicine, Miyazaki, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kamoto
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kamba
authors.affiliation: Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: ogawao@kuhp.kyoto-u.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D018450:Disease Progression; D004961:Estramustine / Q000008:administration & dosage*; D006801:Humans; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004961:Estramustine; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Androgen-deprivation therapy; Docetaxel; Estrogen; PSA; Phase II