title: Standard or accelerated methotrexate, vinblastine, doxorubicin and cisplatin as neoadjuvant chemotherapy for locally advanced urothelial bladder cancer: Does dose intensity matter?
abstract: BACKGROUND
  There is continuing controversy regarding the optimal regimen for neoadjuvant chemotherapy (NAC) in bladder cancer.
  
  
  METHODS
  We performed a retrospective analysis of 241 consecutive bladder cancer patients who received a combination of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) using a standard (52 patients) or an accelerated schedule (189 patients) as NAC before radical cystectomy in 17 centres of the French GEnito-urinary TUmour Group from March 2004-May 2013.
  
  
  RESULTS
  The median age was 62 years. As expected, the median number of cycles, the median total dose of cisplatin and the median cisplatin dose intensity were higher in patients treated with the accelerated regimen. Conversely, the median duration of chemotherapy was shorter. Regarding toxicity, grade III/IV neutropenia, grade III thrombocytopenia and grade III anaemia as well were more frequently observed in patients treated with the standard regimen. Among 211 (88%) patients who proceeded to cystectomy, 75 (35%) patients achieved an ypT0 pN0 status (no pathologic residual tumour cells) with no significant difference according to the MVAC schedule. Three-year overall survival rates were 66.5% (95% confidence interval [CI], 56-79) and 72% (95% CI, 59.5-88) in the standard and accelerated cohorts, respectively. In the multivariate analysis, two independent prognostic parameters were retained: the ypT0 stage and the ypN0 stage. Heterogeneity test did not show any interaction with NAC regimens.
  
  
  CONCLUSIONS
  Similar pathological response and survival rates were observed whatever the chemotherapy regimen used. Haematological toxicity was greater in patients who received standard MVAC.
authors.affiliation: Department of Medical Oncology, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Pouessel
authors.affiliation: Department of Biostatistics and Medical Information, Hôpital Saint-Louis, AP-HP, Paris, France; Inserm, UMR 717, Hôpital Saint-Louis, AP-HP, Paris, France; Paris Diderot University, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.affiliation: Institut de Cancérologie de l'Ouest, Nantes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rolland
authors.affiliation: Institut Paoli Calmettes, Marseille, France.
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Gravis
authors.affiliation: Centre Alexis Vautrin, Nancy, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Geoffrois
authors.affiliation: Institut Bergonié, Bordeaux, France.
authors.forename: Guilhem
authors.initials: G
authors.lastname: Roubaud
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Safae
authors.initials: S
authors.lastname: Terrisse
authors.affiliation: Centre Léon Bérard, Lyon, France.
authors.forename: Helen
authors.initials: H
authors.lastname: Boyle
authors.affiliation: Institut Claudius Régaud, Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Chevreau
authors.affiliation: Centre Hospitalier, Mont-de-Marsan, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Dauba
authors.affiliation: Institut de Cancérologie de la Loire, Saint-Etienne, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Moriceau
authors.affiliation: Centre Médical de Bligny, Briis-sous-Forges, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Alexandre
authors.affiliation: Hôpital Saint-Joseph, Paris, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Deplanque
authors.affiliation: Centre OncoGard, Nîmes, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Chapelle
authors.affiliation: Centre Eugène Marquis, Rennes, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Vauleon
authors.affiliation: Hôpital des Diaconesses, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Colau
authors.affiliation: Hôpital Georges Pompidou, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Audenet
authors.affiliation: Centre Hospitalier Saint-André, Bordeaux, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grellety
authors.affiliation: Department of Medical Oncology, Hôpital Saint-Louis, AP-HP, Paris, France; Paris Diderot University, Paris, France. Electronic address: stephane.culine@aphp.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Culine
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D015653:Cystectomy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005602:France; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000401:mortality; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate
keywords: Dose intensity; Muscle-invasive disease; Neoadjuvant chemotherapy; Transitional cell carcinoma; Urothelial carcinoma