title: Randomized study of three different doses of suramin administered with a fixed dosing schedule in patients with advanced prostate cancer: results of intergroup 0159, cancer and leukemia group B 9480.
abstract: OBJECTIVE
  To test the hypothesis that the efficacy and toxicity of suramin in the treatment of patients with hormone-refractory prostate cancer was dose dependent.
  
  
  METHODS
  Patients were randomized with equal probability to receive low-, intermediate-, or high-dose suramin (total doses 3.192, 5.320, and 7.661 g/m(2), respectively). Overall survival, time to progression, and response rate (prostate-specific antigen [PSA] and objective) for each treatment arm were compared. Relationships between plasma suramin concentrations and response, toxicity, and survival were also evaluated.
  
  
  RESULTS
  Three hundred ninety patients were randomized. For the low-, intermediate-, and high-dose arms, the median survival time was 16, 14, and 13 months, respectively (P =.49). The objective response rate was 9%, 7%, and 15%, respectively (P =.10). PSA response rates were 24%, 28%, and 34%, respectively (P =.082). Landmark analyses of a 50% decline in PSA at 20 weeks showed a significant correlation with survival. There was a dose-response relationship between dose and toxicity. After adjusting for treatment arm, the measured suramin concentration was not associated with clinical response, PSA response, survival, or toxicity.
  
  
  CONCLUSIONS
  Although high-dose suramin was associated with higher objective and PSA response rates, these were not statistically significant. Overall, no dose-response relationship was observed for survival or progression-free survival, but toxicity was increased with the higher dose. Patients treated with the low-dose level experienced modest toxicity, making it the preferred arm on this study. The lack of a dose-response relationship and the toxicity profile observed raise questions regarding the utility of suramin, particularly high-dose suramin, as administered on this schedule.
authors.affiliation: Comprehensive Cancer Center, University of California-San Francisco, 1600 Devisadero Street, Third Floor, San Francisco, CA 94115, USA. smalle@medicine.ucsf.edu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ratain
authors.forename: Gary
authors.initials: G
authors.lastname: Rosner
authors.forename: Walter
authors.initials: W
authors.lastname: Stadler
authors.forename: David
authors.initials: D
authors.lastname: Palchak
authors.forename: Ernest
authors.initials: E
authors.lastname: Marshall
authors.forename: Randall
authors.initials: R
authors.lastname: Rago
authors.forename: Vera
authors.initials: V
authors.lastname: Hars
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Daniel
authors.initials: D
authors.lastname: Petrylak
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D013498:Suramin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D013498:Suramin; D017430:Prostate-Specific Antigen