title: Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924.
abstract: OBJECTIVE
  This randomized trial evaluated antitumor activity of and survival asociated with high-dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC).
  
  
  METHODS
  A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles).
  
  
  RESULTS
  Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete responses (CRs) (21%) and 55 partial responses (PRs) (41%), for an overall response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was.009; and for the overall response, it was.06. There was no statistically significant difference in survival (P =.122) or time to progression (P =.114). Progression-free survival was significantly better with HD-MVAC (P=.037; hazard ratio.75; 95% CI.58 to.98). The median progression-free survival time was 9.1 months on the HD-MVAC arm versus 8.2 months on the MVAC arm. The 2-year progression-free survival rate was 24.7% for HD-MVAC (95% CI, 17.1% to 32.3%) versus 11.6% for MVAC (95% CI, 5.9% to 17.4%).
  
  
  CONCLUSIONS
  With HD-MVAC, it was possible to deliver twice the doses of cisplatin and doxorubicin in half the time, with fewer dose delays and less toxicity. Although a 50% difference in median overall survival was not detected, a benefit was observed in progression-free survival, CR rates, and overall response rates with HD-MVAC.
authors.affiliation: Vincenzo Pansadoro Foundation, Rome, Italy. cstern@mclink.it
authors.forename: C N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: P H
authors.initials: PH
authors.lastname: de Mulder
authors.forename: J H
authors.initials: JH
authors.lastname: Schornagel
authors.forename: C
authors.initials: C
authors.lastname: Théodore
authors.forename: S D
authors.initials: SD
authors.lastname: Fossa
authors.forename: A T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: F
authors.initials: F
authors.lastname: Witjes
authors.forename: M
authors.initials: M
authors.lastname: Spina
authors.forename: C J
authors.initials: CJ
authors.lastname: van Groeningen
authors.forename: C
authors.initials: C
authors.lastname: de Balincourt
authors.forename: L
authors.initials: L
authors.lastname: Collette
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D004317:Doxorubicin; D000069585:Filgrastim; D002945:Cisplatin; D008727:Methotrexate