title: Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder.
abstract: BACKGROUND
  Meta-analysis data demonstrate a 5% absolute survival benefit for neoadjuvant chemotherapy (NAC) using cisplatin-based combination regimens in the radical treatment of muscle-invasive bladder cancer (MIBC). However, there are no randomized, controlled trial data on the optimum regimen. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a dose-intense regimen that has the potential to minimize delays to definitive, potentially curative therapy. A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway.
  
  
  METHODS
  Eighty consecutive patients with MIBC were treated with AMVAC as NAC by 2 UK multidisciplinary uro-oncology teams. Three or 4 cycles of AMVAC (methotrexate 30 mg/m(2) , vinblastine 3 mg/m(2) , doxorubicin 30 mg/m(2) , and cisplatin 70 mg/m(2) ) were given at 2-week intervals, with granulocyte colony-stimulating factor support, prior to either radical surgery or radical radiotherapy.
  
  
  RESULTS
  All planned cycles of chemotherapy were completed, without dose reduction or delay in 84% of patients. All 80 patients subsequently received their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the 42% of patients for whom toxicity data are available, including 12% grade 3/4 neutropenia. Pathological complete response to AMVAC was seen in 43% of 60 surgical patients. Objective radiological local response was seen in 83% of 57 evaluable patients. Two-year disease-free and overall survival were 65% and 77%, respectively.
  
  
  CONCLUSIONS
  AMVAC is safe and appears to be a well-tolerated and effective NAC regimen for MIBC. It minimizes delays to definitive treatment and produces excellent pathological and radiological response rates. It is an appropriate comparator for future randomized trials.
authors.affiliation: Department of Urology, Oxford Cancer Centre, The Churchill Hospital, Oxford, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Blick
authors.forename: Peter
authors.initials: P
authors.lastname: Hall
authors.forename: Thinn
authors.initials: T
authors.lastname: Pwint
authors.forename: Faisal
authors.initials: F
authors.lastname: Al-Terkait
authors.forename: Jeremy
authors.initials: J
authors.lastname: Crew
authors.forename: Thomas
authors.initials: T
authors.lastname: Powles
authors.forename: Valentine
authors.initials: V
authors.lastname: Macaulay
authors.forename: Nicholas
authors.initials: N
authors.lastname: Munro
authors.forename: David
authors.initials: D
authors.lastname: Douglas
authors.forename: Neviana
authors.initials: N
authors.lastname: Kilbey
authors.forename: Andrew
authors.initials: A
authors.lastname: Protheroe
authors.forename: John D
authors.initials: JD
authors.lastname: Chester
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D015653:Cystectomy; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000188:drug therapy; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D012008:Recurrence; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate