title: Single agent 2',2'-difluorodeoxycytidine in the treatment of metastatic urothelial carcinoma: a phase II study.
abstract: OBJECTIVE
  To evaluate the therapeutic activity and toxicity of gemcitabine in the treatment of metastatic urothelial carcinoma.
  
  
  METHODS
  Twenty-four consecutive patients with recurrent- and/or metastatic urothelial carcinoma pretreated with first line cisplatin-based chemotherapy were treated with gemcitabine 1000 mg/m2/week intravenously diluted in 250 cc of normal saline as 20 minutes infusion for 3 consecutive weeks followed by a 1 week rest period. Chemotherapy was repeated every 28 days.
  
  
  RESULTS
  All enrolled patients were evaluable for objective response accordingly to an intent-to-treat analysis. A complete response was achieved in 1 patient (4%) and a partial response in 6 cases (25%) for an overall response rate of 29% (confidence limits 18%-39%). The median duration of objective responses was 7.4+ months (range 3.0+/12.8). Six patients showed no changes (25%) with a median duration of 4.0 months. A subjective improvement in tumor-related symptoms was reported by all responding patients, and in 3 patients with no change. Six out of 9 patients with symptomatic bone lesions had a subjective improvement with reduction in analgesic drugs consumption. Objective responses were observed at all sites of disease. The median overall survival was 13.0+ months (range 4.0/16.2+). Over a total of 76 cycles (a mean of 3.1 cycles/patient), grade 1-2 leukopenia was seen in 9 patients (37%), grade 1-2 thrombocytopenia in 4 patients (17%), and grade 1 anemia in only 2 cases (8%). Grade 3 leukopenia was seen in 3 cases (12.5%). Grade 4 leukopenia or grade 3-4 thrombocytopenia were not seen. Gastrointestinal toxicity was very mild.
  
  
  CONCLUSIONS
  Single agent gemcitabine at the dose of 1000 mg/m2 on a weekly schedule is active, at least in terms of objective response rate and tumor-related symptoms palliation, against pretreated urothelial carcinoma with good tolerability. These results compare favorably with those achieved with the most active drugs such as cisplatin and methotrexate.
authors.affiliation: Division Medical Oncology, Centro Catanese di Oncologia, Catania, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Gebbia
authors.forename: A
authors.initials: A
authors.lastname: Testa
authors.forename: N
authors.initials: N
authors.lastname: Borsellino
authors.forename: G
authors.initials: G
authors.lastname: Mauceri
authors.forename: F
authors.initials: F
authors.lastname: Varvara
authors.forename: M L
authors.initials: ML
authors.lastname: Tirrito
authors.forename: D
authors.initials: D
authors.lastname: Sambataro
authors.forename: G
authors.initials: G
authors.lastname: Fallica
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D009362:Neoplasm Metastasis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine