title: Treatment of patients with metastatic urothelial cancer "unfit" for Cisplatin-based chemotherapy.
abstract: OBJECTIVE
  Cisplatin-based combination chemotherapy is considered standard first-line treatment for patients with metastatic urothelial carcinoma. However, a large proportion of patients with metastatic urothelial carcinoma are considered "unfit" for cisplatin. The purpose of this review is to define unfit patients and to identify treatment options for this subgroup of patients.
  
  
  METHODS
  In this review, the criteria used to define unfit patients are explored and the results of prospective clinical trials evaluating chemotherapeutic regimens in unfit patients are summarized.
  
  
  RESULTS
  Several phase II trials and a single, large phase III trial have explored chemotherapeutic regimens for the treatment of unfit patients with metastatic urothelial carcinoma. Heterogeneous eligibility criteria have been used to define unfit patients in these studies. A uniform definition of unfit is proposed on the basis of the results of a survey of genitourinary medical oncologists. According to this definition, unfit patients would meet at least one of the following criteria: Eastern Cooperative Oncology Group performance status of 2, creatinine clearance less than 60 mL/min, grade ≥ 2 hearing loss, grade ≥ 2 neuropathy, and/or New York Heart Association Class III heart failure.
  
  
  CONCLUSIONS
  Additional studies to optimize treatment for this important subset of patients are needed. A uniform definition of unfit patients will lead to more uniform clinical trials, enhanced ability to interpret the results of these trials, and a greater likelihood of developing a viable strategy for regulatory approval.
authors.affiliation: Mount Sinai School of Medicine, Tisch Cancer Institute, 1 Gustave L. Levy Place, New York, NY 10029, USA. matthew.galsky@mssm.edu
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.forename: Noah M
authors.initials: NM
authors.lastname: Hahn
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosenberg
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Thomas
authors.initials: T
authors.lastname: Hutson
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.forename: Nicholas
authors.initials: N
authors.lastname: Vogelzang
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bajorin
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015897:Comorbidity; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D009362:Neoplasm Metastasis; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D019459:Urothelium / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin