title: Phase II study of sunitinib as first-line treatment of urothelial cancer patients ineligible to receive cisplatin-based chemotherapy: baseline interleukin-8 and tumor contrast enhancement as potential predictive factors of activity.
abstract: BACKGROUND
  A strong rationale supports the role of antiangiogenic drugs in urothelial cancer. This trial was designed to assess the activity of sunitinib as first-line treatment in patients with metastatic urothelial cancer ineligible for cisplatin and to explore molecular and imaging variables predictive of clinical benefit.
  
  
  METHODS
  This was a multicenter phase II trial with sunitinib 50 mg daily in 4/2-week schedule. Eligibility criteria were as follows: creatinine clearance 30-60 ml/min, Eastern Cooperative Oncology Group Pperformance Sstatus of one or less, and adequate hepatic and hematologic function. Twelve circulating cytokines were evaluated at baseline and sequentially using Luminex xMAP(®) (Austin, TX). Baseline and treatment-related changes in perfusion were evaluated in a patient subgroup using contrast-enhanced computed tomography.
  
  
  RESULTS
  On intention-to-treat analysis, 38 patients showed 3 (8%) partial responses (PRs) and 19 (50%) presented with stable disease (SD), 17 (45%) of them ≥3 months. Clinical benefit (PR + SD) was 58%. Median time to progression (TTP) was 4.8 months and median overall survival 8.1 months. Toxicity was consistent with previous reports for sunitinib. Low interleukin-8 (IL-8) baseline levels were significantly associated with increased TTP. Baseline tumor contrast enhancement with >40 Hounsfield units was associated with clinical benefit.
  
  
  CONCLUSIONS
  This study highlights the potential role of the angiogenic pathway as a therapy target in urothelial cancer. Baseline IL-8 serum levels and contrast enhancement of lesions warrant further study.
authors.affiliation: Medical Oncology Service, University Hospital del Mar, Barcelona. Electronic address: jbellmunt@parcdesalutmar.cat.
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Medical Oncology Service, Hospital Clínico San Carlos, Madrid.
authors.forename: J L
authors.initials: JL
authors.lastname: González-Larriba
authors.affiliation: Oncology Division, Centro de Investigación Médica Aplicada, Navarra University, Pamplona.
authors.forename: C
authors.initials: C
authors.lastname: Prior
authors.affiliation: Medical Oncology Service, Hospital de la Santa Creu i Sant Pau, Barcelona.
authors.forename: P
authors.initials: P
authors.lastname: Maroto
authors.affiliation: Medical Oncology Service, University Hospital del Mar, Barcelona.
authors.forename: J
authors.initials: J
authors.lastname: Carles
authors.affiliation: Medical Oncology Service, Hospital 12 de Octubre, Madrid.
authors.forename: D
authors.initials: D
authors.lastname: Castellano
authors.affiliation: Medical Oncology Service, Hospital Clinic de Barcelona, Barcelona.
authors.forename: B
authors.initials: B
authors.lastname: Mellado
authors.affiliation: Medical Oncology Service, Corporació Sanitaria Parc Tauli, Sabadell.
authors.forename: E
authors.initials: E
authors.lastname: Gallardo
authors.affiliation: Medical Oncology Service, Clínica Universitaria de Navarra, Pamplona.
authors.forename: J L
authors.initials: JL
authors.lastname: Perez-Gracia
authors.affiliation: Medical Oncology Service, University Hospital del Mar, Barcelona.
authors.forename: G
authors.initials: G
authors.lastname: Aguilar
authors.affiliation: Medical Oncology Service, University Hospital del Mar, Barcelona.
authors.forename: X
authors.initials: X
authors.lastname: Villanueva
authors.affiliation: Medical Oncology Service, University Hospital del Mar, Barcelona; Cancer Research Program, Institut Municipal d'Investigació Mèdica (Hospital del Mar Research Institute), Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Albanell
authors.affiliation: Oncology Division, Centro de Investigación Médica Aplicada, Navarra University, Pamplona.
authors.forename: A
authors.initials: A
authors.lastname: Calvo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000627:therapeutic use*; D003287:Contrast Media; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D016209:Interleukin-8 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C508606:CXCL8 protein, human; D003287:Contrast Media; D007211:Indoles; D016209:Interleukin-8; D011758:Pyrroles; D002945:Cisplatin; D000077210:Sunitinib