title: Second-Line Treatment of Advanced Urothelial Cancer with Paclitaxel and Everolimus in a German Phase II Trial (AUO Trial AB 35/09).
abstract: OBJECTIVE
  The efficacy of second-line treatment after failure of platinum-based chemotherapy in patients with advanced urothelial cancer is limited. Based on encouraging preclinical and clinical phase I data, we evaluated the safety and efficacy of the combination of paclitaxel and everolimus in these patients.
  
  
  METHODS
  In this trial, patients having failed to respond to prior platinum-based combination treatment of urothelial cancer were treated with paclitaxel (175 mg/m(2) i.v., 3-weekly) and the mTOR-inhibitor everolimus (10 mg p.o., once daily). The patients were treated until tumor progression or until a maximum of 6 cycles was completed. A one-stage design was used to evaluate the objective response rate (ORR) as the primary endpoint.
  
  
  RESULTS
  A total of 27 patients (67% male; median age 63 years) were enrolled. The most frequent grade III/IV toxicities were anemia (28%), peripheral neuropathy (28%), and fatigue (24%). No treatment-related deaths were reported. Complete and partial remissions were observed in 0/24 and 3/24 patients eligible for efficacy analysis, respectively (ORR 13%). Progression-free survival was 2.9 months [95% confidence interval (95% CI) 1.9-4.2], and the median overall survival was 5.6 months (95% CI 4.8-10.2).
  
  
  CONCLUSIONS
  The combination of paclitaxel and everolimus has not achieved the expected efficacy in second-line treatment of urothelial cancer and should not be further explored.
authors.affiliation: Department of Urology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Niegisch
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
authors.forename: Mark
authors.initials: M
authors.lastname: Thalgott
authors.forename: Stefan
authors.initials: S
authors.lastname: Balabanov
authors.forename: Friedemann
authors.initials: F
authors.lastname: Honecker
authors.forename: Carsten Henning
authors.initials: CH
authors.lastname: Ohlmann
authors.forename: Michael
authors.initials: M
authors.lastname: Stöckle
authors.forename: Martin
authors.initials: M
authors.lastname: Bögemann
authors.forename: Frank
authors.initials: F
authors.lastname: Vom Dorp
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gschwend
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Christian
authors.initials: C
authors.lastname: Ohmann
authors.forename: Peter
authors.initials: P
authors.lastname: Albers
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000068338:Everolimus / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D017239:Paclitaxel