title: Phase II trial of suramin, leuprolide, and flutamide in previously untreated metastatic prostate cancer.
abstract: OBJECTIVE
  To assess the efficacy and toxicity of suramin, hydrocortisone, leuprolide, and flutamide in previously untreated metastatic prostate cancer.
  
  
  METHODS
  Patients with stage D2 and poor-prognosis stage D1 prostate cancer were given suramin on a pharmacokinetically derived dosing schedule to maintain suramin concentrations between 175 and 300 micrograms/mL. Additionally, all patients received flutamide 250 mg orally three times daily, initiated on day 1 and continued until disease progression; depot leuprolide 7.5 mg intramuscularly begun on day 5 and repeated every 4 weeks indefinitely; and replacement doses of hydrocortisone.
  
  
  RESULTS
  Fifty patients were entered onto the study: 48 with stage D2 and two with stage D1 disease. The median age was 59 years (range, 42 to 79) and 31 patients had a Karnofsky performance status (KPS) of 100%. Forty-five patients had bone metastases and 25 had measurable soft tissue disease. Forty-one (82%) had severe disease. The overall response rate in 49 assessable patients was three complete responses (CRs) and 30 partial responses (PRs) for an overall response rate of 67%. Eighteen patients have died. The median survival time has not been reached, with a median potential follow-up duration of 44 months. Grade 3 to 4 toxicity was seen in 38% of patients and was predominantly hematologic and reversible.
  
  
  CONCLUSIONS
  The high response rate and prolonged survival in a poor-prognosis group of patients with metastatic prostate cancer warrant a phase III randomized comparison of this regimen versus hormonal therapy alone. Toxicity was moderate and reversible.
authors.affiliation: Division of Clinical Sciences, National Cancer Institute, Bethesda, MD, USA. nancy_a.dawson@wramaa.chcs.amedd.army.mil
authors.forename: N A
authors.initials: NA
authors.lastname: Dawson
authors.forename: W D
authors.initials: WD
authors.lastname: Figg
authors.forename: M R
authors.initials: MR
authors.lastname: Cooper
authors.forename: O
authors.initials: O
authors.lastname: Sartor
authors.forename: R C
authors.initials: RC
authors.lastname: Bergan
authors.forename: A M
authors.initials: AM
authors.lastname: Senderowicz
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: A
authors.initials: A
authors.lastname: Tompkins
authors.forename: B
authors.initials: B
authors.lastname: Weinberger
authors.forename: E A
authors.initials: EA
authors.lastname: Sausville
authors.forename: E
authors.initials: E
authors.lastname: Reed
authors.forename: C E
authors.initials: CE
authors.lastname: Myers
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005485:Flutamide / Q000008:administration & dosage; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D013498:Suramin / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013498:Suramin; D005485:Flutamide; D017430:Prostate-Specific Antigen; D016729:Leuprolide