title: Phase II clinical trial of PM00104 (Zalypsis(®)) in urothelial carcinoma patients progressing after first-line platinum-based regimen.
abstract: OBJECTIVE
  This exploratory phase II clinical trial evaluated the antitumor activity, safety profile and pharmacokinetics of PM00104 (Zalypsis(®)) 3 mg/m(2) 1 h every 3-week intravenous infusion in patients with advanced and/or metastatic urothelial carcinoma progressing after first-line platinum-based chemotherapy.
  
  
  METHODS
  The primary efficacy end point was the disease control rate (DCR), defined as the percentage of patients with confirmed objective response or progression-free at 3 months, according to the response evaluation criteria in solid tumors.
  
  
  RESULTS
  In a first stage (n = 19 patients evaluable for efficacy), only one patient achieved DCR (stable disease as best response and progression-free survival of 3.1 months). According to the 2-stage design used, the primary efficacy objective was unmet, and therefore, the trial was finalized without opening the second stage. The most common adverse events related to PM00104 were fatigue, anorexia, nausea, troponin I increase and neutropenia, which were transient and manageable with dose modifications or administration delays. Mean PK results (Cmax = 48.57 μg/l and area under the curve (AUC) = 154.97 h μg/l) were similar to those observed in a previous phase I trial evaluating the same dose and schedule. Few troponin I concentrations were higher than 0.10 ng/ml, and none of them were related to parameters of PM00104 exposure such as AUC or Cmax.
  
  
  CONCLUSIONS
  No recommendation is given for further evaluation of PM00104 as single-agent treatment of patients with pretreated advanced and/or metastatic urothelial carcinoma. No new safety signals were observed.
authors.affiliation: Hospital Universitario Doce de Octubre, Avda. Córdoba s/n, 28041, Madrid, Spain, cdanicas@hotmail.com.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Castellano
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: José Pablo
authors.initials: JP
authors.lastname: Maroto
authors.forename: Albert
authors.initials: A
authors.lastname: Font-Pous
authors.forename: Rafael
authors.initials: R
authors.lastname: Morales-Barrera
authors.forename: Ismael
authors.initials: I
authors.lastname: Ghanem
authors.forename: Cristina
authors.initials: C
authors.lastname: Suarez
authors.forename: Cristina
authors.initials: C
authors.lastname: Martín Lorente
authors.forename: Olatz
authors.initials: O
authors.lastname: Etxaniz
authors.forename: Laia
authors.initials: L
authors.lastname: Capdevila
authors.forename: Cinthya
authors.initials: C
authors.lastname: Coronado
authors.forename: Vicente
authors.initials: V
authors.lastname: Alfaro
authors.forename: Mariano
authors.initials: M
authors.lastname: Siguero
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Teruel
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D009944:Organoplatinum Compounds; C500383:PM 00104; D044005:Tetrahydroisoquinolines