title: A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience.
abstract: BACKGROUND
  Neoadjuvant cisplatin-based chemotherapy improves survival in muscle-invasive urothelial cancer, with MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) considered the standard regimen. Gemcitabine plus cisplatin (GC) has similar efficacy and less toxicity than MVAC in metastatic disease, but is untested as neoadjuvant treatment.
  
  
  METHODS
  The authors retrospectively evaluated patients with muscle-invasive urothelial carcinoma who received neoadjuvant GC before radical cystectomy between November 2000 and December 2006 at Memorial Sloan-Kettering Cancer Center. Post-therapy pathological downstaging to either residual disease at cystectomy (pT0) or no residual muscle-invasion (<pT2, ie, pT0, pTIS, pT1), chemotherapy delivery, and disease-free survival were the endpoints of interest. For comparison, similar endpoints were assessed in a historical cohort treated with neoadjuvant MVAC.
  
  
  RESULTS
  Four cycles of neoadjuvant GC were given over 12 weeks (n=42). Thirty-nine (93%) of 42 patients received 4 cycles, with a median 91% drug delivery for cisplatin and 90% for gemcitabine. The pT0 proportion was 26% (95% confidence interval [CI], 14-42), and no residual muscle-invasive disease proportion (<pT2) was 36% (95% CI, 21-52); pT0 was achieved in 28% (95% CI, 16-42) and <pT2 in 35% (95% CI, 23-49) of 54 MVAC-treated patients. All 15 GC patients achieving <pT2 pathologic stage remained disease-free at a median follow-up of 30 months.
  
  
  CONCLUSIONS
  Neoadjuvant GC is feasible and allows for timely drug delivery. The proportion of GC-treated patients whose primary tumors were downstaged, with prolonged disease-free survival and minimal or no residual disease, was similar to MVAC-treated patients.
authors.affiliation: Division of Urology, Department of Surgery, Memorial-Sloan Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Atreya
authors.initials: A
authors.lastname: Dash
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Pettus
authors.forename: Harry W
authors.initials: HW
authors.lastname: Herr
authors.forename: Bernard H
authors.initials: BH
authors.lastname: Bochner
authors.forename: Guido
authors.initials: G
authors.lastname: Dalbagni
authors.forename: S Machele
authors.initials: SM
authors.lastname: Donat
authors.forename: Paul
authors.initials: P
authors.lastname: Russo
authors.forename: Mary G
authors.initials: MG
authors.lastname: Boyle
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Milowsky
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bajorin
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D015653:Cystectomy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine