title: The combination of gemcitabine and carboplatin as first-line treatment in patients with advanced urothelial carcinoma. A Phase II study of the Hellenic Cooperative Oncology Group.
abstract: BACKGROUND
  The toxicity of platinum-based combinations represents a common problem for patients with advanced urothelial carcinoma. The authors previously reported encouraging efficacy for the combination of carboplatin and gemcitabine in patients considered to be unfit for cisplatin-based treatment. The objective of the current multicenter Phase II study was to evaluate the safety and efficacy of the combination of gemcitabine and carboplatin as first-line treatment in unselected patients with advanced urothelial carcinoma.
  
  
  METHODS
  Patients with previously untreated, bidimensionally measurable, inoperable or metastatic urothelial carcinoma were treated with carboplatin, area under the concentration curve of 5 (Day 1) and gemcitabine at a dose of 1000 mg/m(2) (Days 1 and 8), every 21 days for a total of 6 cycles.
  
  
  RESULTS
  Sixty patients (49 men and 11 women, with a median age of 69 yrs) were enrolled in the current study. Intent-to-treat analysis demonstrated an objective response rate (ORR) of 38.4% (95% confidence interval [95% CI], 26-51.8%) (11.7% complete responses and 26.7% partial responses). The median time to disease progression was 7.6 months (95% CI, 4.5-10.7 mos) and the median overall survival was 16.3 months (95% CI, 12-20.6 mos). The median survival was comparable to that reported for the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) according to the Memorial Sloan-Kettering Cancer Center prognostic model for patients with similar baseline prognostic features. Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) included anemia (18%), thrombocytopenia (23%), and neutropenia (52%), with 7 episodes of febrile neutropenia (11%) reported. Nonhematologic toxicity was rare. One toxic death occurred during the study.
  
  
  CONCLUSIONS
  The combination of gemcitabine and carboplatin appears to have considerable activity as the first-line treatment of unselected patients with advanced urothelial carcinoma with manageable toxicity, and deserves further evaluation in this setting.
authors.affiliation: Department of Clinical Therapeutics, Athens University, School of Medicine, Athens, Greece. abamias@med.uoa.gr
authors.forename: Aristotle
authors.initials: A
authors.lastname: Bamias
authors.forename: Lia A
authors.initials: LA
authors.lastname: Moulopoulos
authors.forename: Aggelos
authors.initials: A
authors.lastname: Koutras
authors.forename: Gerassimos
authors.initials: G
authors.lastname: Aravantinos
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Dimitris
authors.initials: D
authors.lastname: Pectasides
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.forename: Dimitros
authors.initials: D
authors.lastname: Gika
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Skarlos
authors.forename: Helena
authors.initials: H
authors.lastname: Linardou
authors.forename: Haralambos P
authors.initials: HP
authors.lastname: Kalofonos
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D019459:Urothelium / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine