title: Optimal delivery of perioperative chemotherapy: preliminary results of a randomized, prospective, comparative trial of preoperative and postoperative chemotherapy for invasive bladder carcinoma.
abstract: OBJECTIVE
  We performed a planned interim analysis of a randomized trial comparing initial to postoperative chemotherapy for bladder cancer. The purpose of our analysis was to detect early evidence of survival differences, tolerance to therapy influenced by the sequence of treatment, predictive value of clinical state and influence of methotrexate, vinblastine, doxorubucin and cisplatin (M-VAC) on bladder resectability.
  
  
  METHODS
  A total of 100 consecutive patients were randomized to receive 2 M-VAC courses before and 3 courses after surgery (group 1) or 5 adjuvant M-VAC courses following cystectomy (group 2). Survival, clinical response, clinical and pathological stage, and toxicity were evaluated in this second timed interim analysis.
  
  
  RESULTS
  Of all patients 70% received at least 4 M-VAC courses. Overall survival at 31.7 months (range 1.8 to 87.7) was similar in groups 1 (60%) and 2 (63%), and independent of clinical stage. Preoperative clinical staging accurately identified patients at high risk for recurrence, while 37 of the 48 group 2 patients (77%) were considered at high risk by pathological staging (P3b, P4a, node-positive and unresectable disease). Comparison of pathological stage revealed that 14 of the 51 group 1 patients (28%) achieved stage P0 while only 1 of the 48 group 2 patients (2%) had P0 disease at surgery (p= 0.00043). Disease was unresectable in 3 group 1 (6%) and 8 group 2 patients (17%, p= 0.09). Tolerance to treatment was not significantly different in the 2 study arms.
  
  
  CONCLUSIONS
  No survival advantage was noted between neoadjuvant and adjuvant M-VAC in our interim analysis. However, results suggest that M-VAC chemotherapy may be effective in increasing the resectability of localized bladder cancer and may contribute to organ preservation. Clinical stage was a reliable predictor of pathological findings at surgery. Future studies can use clinical staging to determine therapy before surgery for the select stages that we treated. Identification of the subset likely to achieve complete pathological remission will permit the selection of patients for organ preservation strategies.
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: C
authors.initials: C
authors.lastname: Logothetis
authors.forename: D
authors.initials: D
authors.lastname: Swanson
authors.forename: R
authors.initials: R
authors.lastname: Amato
authors.forename: M
authors.initials: M
authors.lastname: Banks
authors.forename: L
authors.initials: L
authors.lastname: Finn
authors.forename: A
authors.initials: A
authors.lastname: Ayala
authors.forename: J
authors.initials: J
authors.lastname: Ro
authors.forename: R
authors.initials: R
authors.lastname: Babaian
authors.forename: C
authors.initials: C
authors.lastname: Dinney
authors.forename: J
authors.initials: J
authors.lastname: Ellerhorst
authors.forename: C
authors.initials: C
authors.lastname: Hall
authors.forename: A
authors.initials: A
authors.lastname: von Eschenbach
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D015653:Cystectomy; D004317:Doxorubicin / Q000627:therapeutic use; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011182:Postoperative Care; D011300:Preoperative Care; D011446:Prospective Studies; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D014747:Vinblastine / Q000627:therapeutic use
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate