title: Phase II study of everolimus in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract: clinical activity, molecular response, and biomarkers.
abstract: BACKGROUND
  This phase II study assessed the safety and efficacy of everolimus, an oral mammalian target of rapamycin inhibitor in advanced transitional carcinoma cell (TCC) after failure of platinum-based therapy.
  
  
  METHODS
  Thirty-seven patients with advanced TCC received everolimus 10 mg/day until progressive disease (PD) or unacceptable toxicity. The primary end point was the disease control rate (DCR), defined as either stable disease (SD), partial response (PR), or complete response at 8 weeks. Angiogenesis-related proteins were detected in plasma and changes during everolimus treatment were analyzed. PTEN expression and PIK3CA mutations were correlated to disease control.
  
  
  RESULTS
  Two confirmed PR and eight SD were observed, resulting in a DCR of 27% at 8 weeks. Everolimus was well tolerated. Compared with patients with noncontrolled disease, we observed in patients with controlled disease a significant higher baseline level of angiopoietin-1 and a significant early plasma decrease in angiopoietin-1, endoglin, and platelet-derived growth factor-AB. PTEN loss was observed only in patients with PD.
  
  
  CONCLUSIONS
  Everolimus showed clinical activity in advanced TCC. The profile of the plasma angiogenesis-related proteins suggested a role of the everolimus antiangiogenic properties in disease control. PTEN loss might be associated with everolimus resistance.
authors.affiliation: Department of Medical Oncology, Centre du Cancer, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels; Angiogenesis and Cancer Research Laboratory, Pole of Pharmacology and Therapeutics, Université catholique de Louvain, Brussels.
authors.forename: E
authors.initials: E
authors.lastname: Seront
authors.affiliation: Department of Medical Oncology, University Hospital Gent, Gent.
authors.forename: S
authors.initials: S
authors.lastname: Rottey
authors.affiliation: Department of Medical Oncology, Centre Hospitalier Universitaire Sart-Tilman, Liège.
authors.forename: B
authors.initials: B
authors.lastname: Sautois
authors.affiliation: Department of Medical Oncology, Centre Hospitalier Universitaire Mont-Godinne, Namur.
authors.forename: J
authors.initials: J
authors.lastname: Kerger
authors.affiliation: Department of Medical Oncology, Centre Hospitalier Universitaire Mont-Godinne, Namur.
authors.forename: L A
authors.initials: LA
authors.lastname: D'Hondt
authors.affiliation: Department of Medical Oncology, Grand Hôpital de Charleroi, Charleroi.
authors.forename: V
authors.initials: V
authors.lastname: Verschaeve
authors.affiliation: Department of Medical Oncology, Grand Hôpital de Charleroi, Charleroi.
authors.forename: J-L
authors.initials: JL
authors.lastname: Canon
authors.affiliation: Department of Medical Oncology, Réseau Hospitalier de Médecine Sociale, Tournai.
authors.forename: C
authors.initials: C
authors.lastname: Dopchie
authors.affiliation: Department of Medical Oncology, Réseau Hospitalier de Médecine Sociale, Tournai.
authors.forename: J M
authors.initials: JM
authors.lastname: Vandenbulcke
authors.affiliation: Department of Medical Oncology, Clinique Saint-Pierre Ottignies, Ottignies.
authors.forename: N
authors.initials: N
authors.lastname: Whenham
authors.affiliation: Department of Medical Oncology, Centre de Maternité Saint Elisabeth, Namur.
authors.forename: J C
authors.initials: JC
authors.lastname: Goeminne
authors.affiliation: Department of Medical Oncology, Clinique Saint-Luc, Bouge.
authors.forename: M
authors.initials: M
authors.lastname: Clausse
authors.affiliation: Department of Medical Oncology, AZ Klina, Braschaat.
authors.forename: D
authors.initials: D
authors.lastname: Verhoeven
authors.affiliation: Department of Medical Oncology, Clinique Saint Joseph, Arlon.
authors.forename: P
authors.initials: P
authors.lastname: Glorieux
authors.affiliation: Machine Learning Group, Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve.
authors.forename: S
authors.initials: S
authors.lastname: Branders
authors.affiliation: Machine Learning Group, Institute of Information and Communication Technologies, Electronics and Applied Mathematics, Université catholique de Louvain, Louvain-la-Neuve.
authors.forename: P
authors.initials: P
authors.lastname: Dupont
authors.affiliation: Department of radiology, Centre Hospitalier de Jolimont, Haine Saint Paul, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Schoonjans
authors.affiliation: Angiogenesis and Cancer Research Laboratory, Pole of Pharmacology and Therapeutics, Université catholique de Louvain, Brussels.
authors.forename: O
authors.initials: O
authors.lastname: Feron
authors.affiliation: Department of Medical Oncology, Centre du Cancer, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels. Electronic address: jean-pascal.machiels@uclouvain.be.
authors.forename: J-P
authors.initials: JP
authors.lastname: Machiels
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068338:Everolimus; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000068338:Everolimus; D020123:Sirolimus