title: Neoadjuvant induction dose-dense MVAC for muscle invasive bladder cancer: efficacy and safety compared with classic MVAC and gemcitabine/cisplatin.
abstract: OBJECTIVE
  To investigate the efficacy and safety of neoadjuvant induction dose-dense MVAC (dd-MVAC) for muscle invasive bladder cancer (MIBC). Results of the 2-week-per-cycle regimen were compared with classic MVAC (4 weeks per cycle) and gemcitabine/cisplatin (GC, 3 weeks per cycle).
  
  
  METHODS
  We included 166 patients with non-organ-confined MIBC, who received neoadjuvant induction dd-MVAC (80), classic MVAC (35), or GC (51) between 1990 and 2014. Complete pathological response (pCR) was defined as no evidence of residual tumor in cystectomy and lymphadenectomy specimens (ypT0N0). pCR and toxicity rates were compared among regimens.
  
  
  RESULTS
  pCR was found in 29% of dd-MVAC-treated patients, which was not significantly different from classic MVAC (20%, p = 0.366) and GC (32%, p = 0.845). Grade 3-4 toxicity rates related to dd-MVAC and GC (44%) were similar (p = 0.202), whereas the toxicity rate for classic MVAC (55%) was significantly higher than for dd-MVAC (32%) uncorrected (p = 0.026) and corrected for patient and tumor characteristics (OR 2.84, p = 0.037).
  
  
  CONCLUSIONS
  Neoadjuvant induction dd-MVAC resulted in pathological response rates similar to classic MVAC and GC treatment in patients with non-organ-confined MIBC. The shorter cycle duration compared with classic MVAC and GC and the significantly lower toxicity rate compared with classic MVAC indicate that dd-MVAC should be the preferred option for neoadjuvant induction treatment.
authors.affiliation: Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. e.fransen@nki.nl.
authors.forename: Elisabeth E Fransen
authors.initials: EE
authors.lastname: van de Putte
authors.affiliation: Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Mertens
authors.affiliation: Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.|Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Meijer
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Michiel S
authors.initials: MS
authors.lastname: van der Heijden
authors.affiliation: Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Axel
authors.initials: A
authors.lastname: Bex
authors.affiliation: Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Henk G
authors.initials: HG
authors.lastname: van der Poel
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: J Martijn
authors.initials: JM
authors.lastname: Kerst
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Andries M
authors.initials: AM
authors.lastname: Bergman
authors.affiliation: Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Simon
authors.initials: S
authors.lastname: Horenblas
authors.affiliation: Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Bas W G
authors.initials: BW
authors.lastname: van Rhijn
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / 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; Dose dense; MVAC; Neoadjuvant chemotherapy