title: Prospective, open-label, randomized, phase III study of two dose-dense regimens MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or relapsed urothelial cancer: a Hellenic Cooperative Oncology Group study (HE 16/03).
abstract: BACKGROUND
  The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC.
  
  
  METHODS
  One hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events).
  
  
  RESULTS
  The median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%).
  
  
  CONCLUSIONS
  Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population. Clinical Trial Number ACTRN12610000845033, www.anzctr.org.au.
authors.affiliation: Department of Clinical Therapeutics, Alexandra Hospital, Athens University Medical School, Athens, Greece. abamias@med.uoa.gr
authors.forename: A
authors.initials: A
authors.lastname: Bamias
authors.forename: U
authors.initials: U
authors.lastname: Dafni
authors.forename: A
authors.initials: A
authors.lastname: Karadimou
authors.forename: E
authors.initials: E
authors.lastname: Timotheadou
authors.forename: G
authors.initials: G
authors.lastname: Aravantinos
authors.forename: A
authors.initials: A
authors.lastname: Psyrri
authors.forename: I
authors.initials: I
authors.lastname: Xanthakis
authors.forename: M
authors.initials: M
authors.lastname: Tsiatas
authors.forename: V
authors.initials: V
authors.lastname: Koutoulidis
authors.forename: C
authors.initials: C
authors.lastname: Constantinidis
authors.forename: C
authors.initials: C
authors.lastname: Hatzimouratidis
authors.forename: E
authors.initials: E
authors.lastname: Samantas
authors.forename: A
authors.initials: A
authors.lastname: Visvikis
authors.forename: M
authors.initials: M
authors.lastname: Chrisophos
authors.forename: K
authors.initials: K
authors.lastname: Stravodimos
authors.forename: C
authors.initials: C
authors.lastname: Deliveliotis
authors.forename: A
authors.initials: A
authors.lastname: Eleftheraki
authors.forename: D
authors.initials: D
authors.lastname: Pectasides
authors.forename: G
authors.initials: G
authors.lastname: Fountzilas
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D019459:Urothelium / Q000473:pathology* / Q000601:surgery; D014747:Vinblastine / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate; D000093542:Gemcitabine