title: Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer.
abstract: BACKGROUND
  Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting.
  
  
  METHODS
  Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC.
  
  
  RESULTS
  In total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P = .77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P = .48).
  
  
  CONCLUSIONS
  Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice.
authors: Department of Hematology and Medical Oncology, Mount Sinai Medical Center, New York, New York.
authors: Matthew D
authors: MD
authors: Galsky
authors: Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California.
authors: Sumanta K
authors: SK
authors: Pal
authors: Department of Urology, Guy's and St. Thomas' Hospital, London, United Kingdom.
authors: Simon
authors: S
authors: Chowdhury
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Lauren C
authors: LC
authors: Harshman
authors: Department of Medical Oncology, Southampton General Hospital, Southampton, United Kingdom.
authors: Simon J
authors: SJ
authors: Crabb
authors: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors: Yu-Ning
authors: YN
authors: Wong
authors: Division of Oncology, Department of Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Evan Y
authors: EY
authors: Yu
authors: Department of Medical Oncology, Barts Cancer Institute, London, United Kingdom.
authors: Thomas
authors: T
authors: Powles
authors: Division of Biostatistics, Department of Preventative Medicine, Mount Sinai Medical Center, New York, New York.
authors: Erin L
authors: EL
authors: Moshier
authors: Department of Medical Oncology, Georges François Leclerc Center, Dijon, France.
authors: Sylvain
authors: S
authors: Ladoire
authors: Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors: Syed A
authors: SA
authors: Hussain
authors: Department of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors: Neeraj
authors: N
authors: Agarwal
authors: Department of Hematology and Oncology, Barbara Ann Karmanos Cancer Center, Detroit, Michigan.
authors: Ulka N
authors: UN
authors: Vaishampayan
authors: Department of Medical Oncology, Samuel and Barbara Sternberg Cancer Research Foundation, Rome, Italy.
authors: Federica
authors: F
authors: Recine
authors: Department of Medical Oncology, University Hospital of Lausanne, Lausanne, Switzerland.
authors: Dominik
authors: D
authors: Berthold
authors: Department of Medical Oncology, Foundation IRCCS National Cancer Institute, Milan, Italy.
authors: Andrea
authors: A
authors: Necchi
authors: Department of Oncology, Hospital Foch, Suresnes, France.
authors: Christine
authors: C
authors: Theodore
authors: Division of Hematology and Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.
authors: Matthew I
authors: MI
authors: Milowsky
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Joaquim
authors: J
authors: Bellmunt
authors: Division of Genitourinary Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Jonathan E
authors: JE
authors: Rosenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D019042:Muscle Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D014747:Vinblastine / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate; D000093542:Gemcitabine
keywords: bladder cancer; cisplatin; doxorubicin; gemcitabine plus cisplatin; methotrexate; muscle invasion; neoadjuvant; plus cisplatin; vinblastine