title: A phase II study of YM155, a novel small-molecule suppressor of survivin, in castration-resistant taxane-pretreated prostate cancer.
abstract: BACKGROUND
  YM155, a small-molecule survivin suppressor, showed modest single-agent activity in a phase I study of heavily pretreated patients. This study was conducted to determine the activity of YM155 in patients with castration-resistant prostate cancer (CRPC) who received prior taxane therapy.
  
  
  METHODS
  Patients received 4.8 mg/m(2)/day of YM155 over 168-h continuous i.v. infusion every 3 weeks. Study end points included prostate-specific antigen (PSA) response, objective tumor response, safety, progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  Thirty-five patients were enrolled. Two of 32 (6.2%) assessable patients had a PSA response and 2 additional patients had PSA decrements >50% but not confirmed. One of 16 (6.2%) patients also had a partial response per RECIST V1. Median PFS and OS were 3.1 and 11.2 months, respectively. The most common adverse events were fatigue (63%), nausea (40%), anorexia (31%), constipation (31%), fever (26%) and vomiting (26%).
  
  
  CONCLUSIONS
  YM155 has modest activity in taxane-pretreated CRPC with 25% of patients having prolonged stable disease (≥18 weeks). The regimen appears to be well tolerated. Based on the mechanism of action and preclinical evidence of synergy with docetaxel (Taxotere), YM155 combined with docetaxel is being evaluated in patients with CRPC.
authors.affiliation: Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, USA. atolcher@start.stoh.com
authors.forename: A W
authors.initials: AW
authors.lastname: Tolcher
authors.forename: D I
authors.initials: DI
authors.lastname: Quinn
authors.forename: A
authors.initials: A
authors.lastname: Ferrari
authors.forename: F
authors.initials: F
authors.lastname: Ahmann
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
authors.forename: T
authors.initials: T
authors.lastname: Drake
authors.forename: A
authors.initials: A
authors.lastname: Keating
authors.forename: J S
authors.initials: JS
authors.lastname: de Bono
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009285:Naphthoquinones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D000077022:Survivin; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D001952:Bridged-Ring Compounds; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D000077022:Survivin; D043823:Taxoids; C080625:taxane; D017430:Prostate-Specific Antigen; C523798:sepantronium