title: Prospective study of estramustine phosphate for hormone refractory prostate cancer patients following androgen deprivation therapy.
abstract: BACKGROUND
  Estramustine phosphate (EMP) in combination with other cytotoxic agents has been widely used in clinical trials as an anti-tumor agent for the treatment of hormone-refractory prostate cancer (HRPC). However, few prospective studies have considered the efficacy of EMP monotherapy for HRPC patients following androgen-deprivation therapy (ADT), given the availability of methods to measure prostate-specific antigen (PSA) levels in the serum. We therefore initiated a prospective study to determine whether EMP is efficient for HRPC following ADT using changes in PSA levels as the major endpoint.
  
  
  METHODS
  After a diagnosis of anti-androgen withdrawal syndrome had been excluded, 34 patients with HRPC who showed an elevated serum PSA level in 3 or more sequential tests following ADT were treated orally with 560 mg/day of EMP. The clinical stage and the median PSA value for inclusion in the study were D2 and 25.9 (range 6.5-540.8) ng/ml, respectively. Treatment was continued until evidence of disease progression reappeared or until severe adverse effects appeared.
  
  
  RESULTS
  Of the 34 patients enrolled, 29 were evaluated, while the other 5 (15%) patients were discontinued due to severe gastrointestinal side effects. Seven of the 29 patients (24%) showed a decrease of 50% or greater in serum PSA levels from the initially elevated values, with the median duration of PSA response being 8.0 (range 2.2-18.8) months. Baseline PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase, performance status, and length of time of initial hormonal treatment did not correlate with the PSA response. With a median follow-up time of 20.0 (range 3.2-45.6) months, the cancer-specific survival rate at 2 years was 83% in the PSA responders and 44% in the non-responders. The PSA response was correlated with cancer-specific survival (p = 0.029).
  
  
  CONCLUSIONS
  Following ADT one quarter of HRPC patients responded to EMP, with more than 50% of patients showing a decrease in PSA levels and an enhanced survival rate.
authors.affiliation: Department of Urology, Nihon University School of Medicine, Tokyo, Japan. byd04561@nifty.com
authors.forename: Daisaku
authors.initials: D
authors.lastname: Hirano
authors.forename: Sadatsugu
authors.initials: S
authors.lastname: Minei
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kishimoto
authors.forename: Kenya
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hachiya
authors.forename: Toshio
authors.initials: T
authors.lastname: Yoshida
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Endoh
authors.forename: Yataroh
authors.initials: Y
authors.lastname: Yamanaka
authors.forename: Tadao
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Satoh
authors.forename: Hajime
authors.initials: H
authors.lastname: Ishida
authors.forename: Kiyoki
authors.initials: K
authors.lastname: Okada
authors.forename: Yukie
authors.initials: Y
authors.lastname: Takimoto
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D018450:Disease Progression; D004961:Estramustine / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D004961:Estramustine; D017430:Prostate-Specific Antigen