title: Pazopanib in advanced and platinum-resistant urothelial cancer: an open-label, single group, phase 2 trial.
abstract: BACKGROUND
  The development of new drugs for patients with refractory urothelial cancer is still an unmet medical need. Preclinical evidence lends support to a rationale for targeting of the VEGF or platelet-derived growth-factor axis. We therefore investigated the activity and safety of pazopanib, a multitarget drug with antiangiogenic activity, in patients with urothelial cancer.
  
  
  METHODS
  In an open-label, single-group, phase 2 study, patients (aged ≥18 years) with relapsed or refractory urothelial cancer were given pazopanib 800 mg per day, orally. They were treated until disease progression or prohibitive toxicity occurred. The primary endpoint was the proportion of patients who achieved a confirmed objective response, defined as complete or partial response, after independent review, and was analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01031875.
  
  
  RESULTS
  The trial has been completed. 21 (51%) of 41 patients enrolled were given pazopanib as third-line or further-line treatment. 26 (63%) patients had an Eastern Cooperative Oncology Group performance status of 1 or 2. Seven patients had a confirmed objective response (17·1%, 95% CI 7·2-32·1), all of which were partial responses. The most frequent treatment-related grade 3 adverse events were hypertension (three [7%]), fatigue (two [5%]), and gastrointestinal and vaginal fistulisations (two each [5%]). One patient died as a result of duodenal fistulisation that was related to tissue response of bulky tumour masses.
  
  
  CONCLUSIONS
  Pazopanib has single-agent activity in patients with heavily pretreated metastatic urothelial cancer, and warrants further study in this setting. Particular attention should be paid to patients with bulky tumour masses adjacent to viscera because fistulisation is probably related to the response to pazopanib and is the most frequent serious adverse event.
  
  
  BACKGROUND
  Fondazione IRCCS Istituto Nazionale dei Tumori provided the grant. GlaxoSmithKline provided the study drug and provided funding for the independent radiological review.
authors: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. andrea.necchi@istitutotumori.mi.it
authors: Andrea
authors: A
authors: Necchi
authors: Luigi
authors: L
authors: Mariani
authors: Nadia
authors: N
authors: Zaffaroni
authors: Lawrence H
authors: LH
authors: Schwartz
authors: Patrizia
authors: P
authors: Giannatempo
authors: Flavio
authors: F
authors: Crippa
authors: Carlo
authors: C
authors: Morosi
authors: Rodolfo
authors: R
authors: Lanocita
authors: Teodoro
authors: T
authors: Sava
authors: Cinzia
authors: C
authors: Ortega
authors: Caterina
authors: C
authors: Messina
authors: Cosimo
authors: C
authors: Sacco
authors: Marzia
authors: M
authors: Pennati
authors: Maria G
authors: MG
authors: Daidone
authors: Nicola
authors: N
authors: Nicolai
authors: Filippo
authors: F
authors: De Braud
authors: Alessandro M
authors: AM
authors: Gianni
authors: Roberto
authors: R
authors: Salvioni
mesh_terms: D000284:Administration, Oral; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007191:Indazoles; D007558:Italy; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D002945:Cisplatin