title: A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer.
abstract: OBJECTIVE
  17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with antiproliferative activity in several mouse xenograft models, including prostate cancer models. A two-stage phase II study was conducted to assess the activity and toxicity profile of 17-AAG administered to patients with metastatic, hormone-refractory prostate cancer.
  
  
  METHODS
  Patients with at least one prior systemic therapy and a rising prostate-specific antigen (PSA) were eligible. Patients received 17-AAG at a dose of 300 mg/m2 i.v. weekly for 3 of 4 weeks. The primary objective was to assess the PSA response. Secondary objectives were to determine overall survival, to assess toxicity, and to measure interleukin-6, interleukin-8, and maspin levels and quality of life.
  
  
  RESULTS
  Fifteen eligible patients were enrolled. The median age was 68 years and the median PSA was 261 ng/mL. Patients received 17-AAG for a median number of two cycles. Severe adverse events included grade 3 fatigue (four patients), grade 3 lymphopenia (two patients), and grade 3 back pain (two patients). The median PSA progression-free survival was 1.8 months (95% confidence interval, 1.3-3.4 months). The 6-month overall survival was 71% (95% confidence interval, 52-100%).
  
  
  CONCLUSIONS
  17-AAG did not show any activity with regard to PSA response. Due to insufficient PSA response, enrollment was stopped at the end of first stage per study design. The most significant severe toxicity was grade 3 fatigue. Further evaluation of 17-AAG at a dose of 300 mg/m2 i.v. weekly as a single agent in patients with metastatic, hormone-refractory prostate cancer who received at least one prior systemic therapy is not warranted.
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA. heathe@karmanos.org
authors.forename: Elisabeth I
authors.initials: EI
authors.lastname: Heath
authors.forename: David W
authors.initials: DW
authors.lastname: Hillman
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
authors.forename: Shijie
authors.initials: S
authors.lastname: Sheng
authors.forename: Fazlul
authors.initials: F
authors.lastname: Sarkar
authors.forename: Felicity
authors.initials: F
authors.lastname: Harper
authors.forename: Melvin
authors.initials: M
authors.lastname: Gaskins
authors.forename: Henry C
authors.initials: HC
authors.lastname: Pitot
authors.forename: Winston
authors.initials: W
authors.lastname: Tan
authors.forename: S Percy
authors.initials: SP
authors.lastname: Ivy
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
authors.forename: Glenn
authors.initials: G
authors.lastname: Liu
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016227:Benzoquinones / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007118:Immunoassay; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood / Q000187:drug effects; D053208:Kaplan-Meier Estimate; D047029:Lactams, Macrocyclic / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011788:Quality of Life; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D015850:Interleukin-6; D016209:Interleukin-8; D047029:Lactams, Macrocyclic; C085344:SERPIN-B5; D015843:Serpins; C112765:tanespimycin; D017430:Prostate-Specific Antigen