title: Phase II trial of adjuvant gemcitabine plus cisplatin-based chemotherapy in patients with locally advanced bladder cancer.
abstract: BACKGROUND
  Despite the general acceptance of gemcitabine/cisplatin in metastatic bladder cancer, its role and tolerability in the adjuvant setting, in which renal insufficiency is common, is unclear.
  
  
  METHODS
  A total of 39 patients with locally advanced transitional cell carcinoma of the bladder (T2-T4, N0-N2) were treated with 4 cycles of gemcitabine/cisplatin/amifostine after radical cystectomy. All toxicities were evaluated by the National Cancer Institute Common Toxicity Criteria. Tumor samples were immunohistochemically stained for pRB, p53, and p16.
  
  
  RESULTS
  Thirty-five patients (90%) completed 4 cycles of chemotherapy. Eleven patients (28%) experienced grade 4 hematologic toxicity, and 14 patients (36%) experienced grade 3 nonhematologic toxicity. The median increase in creatinine was 0.3 mg/dL. With a median follow-up of 22.8 months (range, 7-70 months), 13 patients (33%) had recurrent disease, 1 patient at 6 years after completion of therapy. Twelve patients (31%) died, including 11 (28%) with recurrent disease. Thirty-three tumor blocks were evaluated for pRB, p53, and p16 alterations. In an exploratory analysis, altered expression of p53, p16, and pRB was found in 15 (45%), 22 (67%), and 30 patients (91%), respectively. No association between altered p53 and disease-free or overall survival was detected, but altered p16 and pRB expression was associated with better outcome (P < or = 0.001).
  
  
  CONCLUSIONS
  Gemcitabine/cisplatin with amifostine is tolerated in the adjuvant setting for patients with locally advanced bladder cancer. The favorable prognostic value of altered p16 and pRB raises the hypothesis of a relative beneficial effect of chemotherapy in this population but needs verification in other studies.
authors.affiliation: Section of Hematology/Oncology, University of Chicago, IL 60637, USA.
authors.forename: James O
authors.initials: JO
authors.lastname: Jin
authors.forename: Jan
authors.initials: J
authors.lastname: Lehmann
authors.forename: Jerome
authors.initials: J
authors.lastname: Taxy
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
authors.forename: Michael
authors.initials: M
authors.lastname: Stöckle
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.forename: Gary
authors.initials: G
authors.lastname: Steinberg
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016160:Retinoblastoma Protein / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine