title: Suramin in hormone-refractory metastatic prostate cancer: a drug with limited efficacy.
abstract: OBJECTIVE
  To confirm the previously reported high response rates and prolonged survival in hormone-refractory prostate cancer treated with suramin.
  
  
  METHODS
  Thirty-six eligible patients with hormone-refractory prostate cancer with either measurable disease or bone disease only and a prostate-specific antigen (PSA) level greater than 50 ng/mL were enrolled. Treatment consisted of two 8-week courses of outpatient-based therapy with an interposed rest period. A bayesian adaptive control strategy and a three-compartment pharmacokinetic model that accommodates clearance changes was used to guide individual dosing. A rapid infusion of 1,000 mg/m2 suramin was followed by five daily infusions that targeted 285 micrograms/mL peak plasma levels during the first week. All patients received concomitant hydrocortisone. For the next 7 weeks, patients received one to two doses per week that targeted levels in the 150 to 285 micrograms/mL range and integrated weekly averages of 200 ug/mL.
  
  
  RESULTS
  Nine patients (28%) had a partial response to suramin based on a > or = 50% decrease in PSA levels coupled with either relief of bone pain or by a 50% decrease in measurable disease. The median overall survival time for all patients is 31 weeks (95% confidence interval [CI], 23 to 51). Treatment was generally well tolerated, with fatigue being the most common significant toxicity, but fatal idiosyncratic myelosuppression (grade V) was observed in one patient.
  
  
  CONCLUSIONS
  Using this dosing schedule, suramin has limited activity against hormone-refractory metastatic prostate cancer. Recent data suggest that hydrocortisone administered with suramin may be partly responsible for the benefit attributed to the drug. Although a small cohort of patients appeared to benefit, we were unable to confirm the previously reported high rate of activity and durability of remission using this agent.
authors.affiliation: Department of Medicine, University of California Los Angeles School of Medicine 90095-7059, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Rosen
authors.forename: E F
authors.initials: EF
authors.lastname: Mendoza
authors.forename: E M
authors.initials: EM
authors.lastname: Landaw
authors.forename: B
authors.initials: B
authors.lastname: Mondino
authors.forename: M C
authors.initials: MC
authors.lastname: Graves
authors.forename: J H
authors.initials: JH
authors.lastname: McBride
authors.forename: P
authors.initials: P
authors.lastname: Turcillo
authors.forename: J
authors.initials: J
authors.lastname: deKernion
authors.forename: A
authors.initials: A
authors.lastname: Belldegrun
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D000553:Ambulatory Care; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013498:Suramin / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D016019:Survival Analysis
chemical_list: D013498:Suramin; D017430:Prostate-Specific Antigen