title: Suramin in combination with weekly epirubicin for patients with advanced hormone-refractory prostate carcinoma.
abstract: BACKGROUND
  Suramin and epirubicin are both active agents in the treatment of patients with hormone-refractory advanced prostate carcinoma, with demonstrated antitumor synergism in vitro on human prostate carcinoma cells and different dose-limiting toxicities. The authors conducted this Phase II study to determine the feasibility, toxicity, and antitumor activity of suramin in combination with epirubicin.
  
  
  METHODS
  Only patients with hormone-independent advanced prostate carcinoma who had progressive disease after the last therapeutic maneuver they had undergone, including antiandrogen withdrawal, entered the study. Suramin was administered initially as a 6-day continuous infusion for 10 consecutive weeks and then for 6 days every 28 days for a maximum of 6 months. Doses were determined by a computer-assisted dosing system that used Bayesian pharmacokinetics to maintain suramin plasma concentrations of 200-250 microg/mL. Cortisone acetate 25 mg, administered at 8 a.m. and 8 p.m. daily, was begun 4 weeks after the initiation of suramin therapy. Epirubicin 25 mg/m2 was given as a weekly intravenous bolus beginning on Day 1 and was continued for a maximum of 6 months.
  
  
  RESULTS
  Twenty-six patients entered the study. Toxicities mainly included World Health Organization Grade 1-2 nausea, fatigue, anorexia, neutropenia, peripheral neuropathy, creatinine elevation, proteinuria, and prolonged prothrombin time, whereas Grade 3 toxicities were uncommon. Among 11 patients with measurable disease, 3 (27%) demonstrated an objective response. Among 24 patients evaluated for prostate specific antigen (PSA) response, 8 (33%; 95% confidence interval 16-55%) had a > or =50% decrease in PSA levels, which lasted a median of 32 (range, 8-52) weeks. Median progression free and overall survival were both 8 months.
  
  
  CONCLUSIONS
  The combination of suramin and epirubicin used in the current study is feasible, is associated with moderate toxicities, and has antitumor activity in advanced hormone-refractory prostate carcinoma. However, the results obtained with this combination do not represent major improvements in the treatment of patients with this disease, compared with suramin or epirubicin alone or other available treatments.
authors.affiliation: U.O. Oncologia Medica, Ospedale S. Chiara, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: A
authors.initials: A
authors.lastname: Antonuzzo
authors.forename: R
authors.initials: R
authors.lastname: Danesi
authors.forename: G
authors.initials: G
authors.lastname: Allegrini
authors.forename: L
authors.initials: L
authors.lastname: Monica
authors.forename: E
authors.initials: E
authors.lastname: Pfanner
authors.forename: G
authors.initials: G
authors.lastname: Masi
authors.forename: S
authors.initials: S
authors.lastname: Ricci
authors.forename: M
authors.initials: M
authors.lastname: Del Tacca
authors.forename: P
authors.initials: P
authors.lastname: Conte
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001499:Bayes Theorem; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013498:Suramin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D015251:Epirubicin; D013498:Suramin; D017430:Prostate-Specific Antigen