title: Irofulven demonstrates clinical activity against metastatic hormone-refractory prostate cancer in a phase 2 single-agent trial.
abstract: BACKGROUND
  The primary objective of this study was to assess the antitumor activity of irofulven in patients with hormone-refractory prostate cancer by measuring a sustained decrease of 50% or greater in serum prostate-specific antigen (PSA) levels.
  
  
  METHODS
  Forty-two patients (median age, 73 years) received at least 1 dose of 10.6 mg/m2 irofulven per day on days 1-5 of a 28-day course. Eligible patients had pathologically confirmed metastatic hormone-refractory adenocarcinoma of the prostate and had not received prior cytotoxic chemotherapy.
  
  
  RESULTS
  Forty-two patients received a median of 3 courses of irofulven. Thirty-two patients received at least 2 courses of therapy and were evaluable for efficacy. Four patients (13%) achieved partial response, with a median duration of 2.9 months (range, 2.6-5.8 months). Twenty-seven patients (84%) had disease stabilization and 1 patient (3%) progressed on study. Median progression-free survival was 3.2 months (95% confidence interval, 2.3-4.2 months), with a median progression-free survival of 4.2 months (range, 3.5-6.9 months) for responders. Grade 4 toxicities consisted of thrombocytopenia, anemia, and neutropenia, occurring in 1 patient each. The most common treatment-related grade 3 nonhematologic toxicities included asthenia (19% of patients), vomiting (14%), nausea (12%), and infection without grade 3/4 neutropenia (10%).
  
  
  CONCLUSIONS
  Irofulven shows activity in hormone-refractory prostate cancer and has an acceptable safety profile, warranting further investigation of this drug, particularly in combination therapies.
authors.affiliation: Texas Oncology, PA, US Oncology, Dallas, Texas 75246, USA. Neil.senzer@usoncology.com
authors.forename: Neil
authors.initials: N
authors.lastname: Senzer
authors.forename: James
authors.initials: J
authors.lastname: Arsenau
authors.forename: Donald
authors.initials: D
authors.lastname: Richards
authors.forename: Barry
authors.initials: B
authors.lastname: Berman
authors.forename: John R
authors.initials: JR
authors.lastname: MacDonald
authors.forename: Sheri
authors.initials: S
authors.lastname: Smith
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D012717:Sesquiterpenes / Q000627:therapeutic use*; D016019:Survival Analysis
chemical_list: D018906:Antineoplastic Agents, Alkylating; D012717:Sesquiterpenes; C102714:irofulven; D017430:Prostate-Specific Antigen