title: Prospective study on the relationship between clinical efficacy of secondary hormone therapy with flutamide and neuroendocrine differentiation in patients with relapsed prostate cancer after first line hormone therapy.
abstract: OBJECTIVE
  The aim of this study was to prospectively verify the relationship between the clinical efficacies of secondary hormone therapy for castration-resistant prostate cancer (CRPC) following first line hormone therapy and neuroendocrine differentiation (NED).
  
  
  METHODS
  Forty-six consecutive patients with CRPC following first line hormone therapy who were treated with flutamide as secondary hormone therapy were prospectively assessed with a median follow-up of 21 months. Serum chromogranin A (CgA), as a marker of NED, was measured using an immunoradiometric assay.
  
  
  RESULTS
  Of the 46 patients, 22 (48%) responded to the secondary hormone therapy as a 50% or more reduction from baseline prostate-specific antigen (PSA) with a median response duration of 9.2 months. The PSA response group was correlated with significantly favorable cancer-specific survival (CSS) (92% vs 59% at 5 years, p = 0.0146) compared with the non-response group. Above-normal CgA levels at study entry were detected in 15 patients (33%), but no association with CSS was identified. Data on CgA kinetics were available in 35 patients. The CgA levels before and at 3 months during the treatment were similar. However, eight patients (23%) with an increase in CgA level of a quarter or more from baseline had a tendency for worse CSS (63% vs 84% at 5 years, p = 0.0507) compared with the remaining patients.
  
  
  CONCLUSIONS
  Within limitations, in this study secondary hormone therapy with flutamide was effective for CRPC following first line hormone therapy. The above-normal CgA level in the first hormone resistance phase is mostly unrelated to prognosis. However, some patients with a remarkable increase in CgA in a short duration may have an unfavorable prognosis caused by NED as well.
authors.affiliation: Department of Urology, Higashi-matsuyama City Municipal Hospital , Higashi-matsuyama Saitama-ken , Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Hirano
authors.forename: Ryo
authors.initials: R
authors.lastname: Hasegawa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Satoh
authors.forename: Junichi
authors.initials: J
authors.lastname: Mochida
authors.forename: Yataroh
authors.initials: Y
authors.lastname: Yamanaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hirakata
authors.forename: Kenya
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Shuji
authors.initials: S
authors.lastname: Sugimoto
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kawata
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D053379:Chromogranin A / Q000097:blood; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D055099:Neuroendocrine Cells / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D053379:Chromogranin A; D005485:Flutamide
keywords: castration-resistant prostate cancer; chromogranin A; flutamide; neuroendocrine differentiation; second line hormone therapy