title: Suramin and hydrocortisone: determining drug efficacy in androgen-independent prostate cancer.
abstract: OBJECTIVE
  The combination of suramin and hydrocortisone has shown clinical benefit in patients with androgen-independent prostate cancer. Widespread use was limited by the complex dose schedules and the need for pharmacologic monitoring. This study reports three sequential pharmacokinetically derived treatment regimens that simplified the administration of suramin and hydrocortisone with reduced toxicity.
  
  
  METHODS
  Three cohorts of patients with advanced prostate cancer that progressed despite castrate levels of testosterone received oral hydrocortisone plus suramin administered in the following manners: (1) a loading dose of suramin followed by a continuous infusion using an adaptive control program (cohort A); (2) an intermittent schedule using a simplified adaptive control schedule (cohort B); and (3) an empiric dosing regimen (cohort C). Drug concentrations were monitored along with the toxicities associated with each regimen. Efficacy was assessed using measurable-disease criteria, radionuclide scans, and posttherapy changes in prostate-specific antigen (PSA) levels.
  
  
  RESULTS
  Fifty-six patients were treated and plasma suramin concentrations were similar for each regimen. A partial response was observed in 4% (one of 28; 95% confidence interval, 0% to 18.4%) of patients with measurable disease, while 12% (six of 50; 95% confidence interval, 4.5% to 24.3%) had a greater than 80% decline in the baseline PSA level. The median duration of response was 12 months. No responses on radionuclide scans were seen. Anemia and lymphocytopenia were the most common toxicities, while 7% of patients developed a sensory or motor neurotoxicity. In the sequential regimens, the frequency of renal insufficiency (P = .04) and coagulopathy (P < .0001) decreased, while transaminase elevations (P = .05) were more common using intermittent infusions (cohorts B and C) versus continuous infusion schedules (cohort A).
  
  
  CONCLUSIONS
  The administration of suramin was simplified and the drug concentrations were maintained. In this cohort of patients with advanced prostate cancer, the clinical activity of suramin using these dosing schedules was limited. Pharmacodynamic issues, patients selection, and criteria to assess efficacy could have effected the clinical outcome.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Kelly
authors.forename: H I
authors.initials: HI
authors.lastname: Scher
authors.forename: M
authors.initials: M
authors.lastname: Mazumdar
authors.forename: D
authors.initials: D
authors.lastname: Pfister
authors.forename: T
authors.initials: T
authors.lastname: Curley
authors.forename: C
authors.initials: C
authors.lastname: Leibertz
authors.forename: L
authors.initials: L
authors.lastname: Cohen
authors.forename: V
authors.initials: V
authors.lastname: Vlamis
authors.forename: A
authors.initials: A
authors.lastname: Dnistrian
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D000222:Adaptation, Physiological; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D015331:Cohort Studies; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D012074:Remission Induction; D013498:Suramin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013739:Testosterone / Q000378:metabolism*
chemical_list: D013739:Testosterone; D013498:Suramin; D006854:Hydrocortisone