title: Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group.
abstract: OBJECTIVE
  The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) represents the standard regimen for inoperable or metastatic urothelial cancer, but its toxicity is significant. We previously reported a 52% response rate (RR) using a docetaxel and cisplatin (DC) combination. The toxicity of this regimen compared favorably with that reported for MVAC. We thus designed a randomized phase III trial to compare DC with MVAC.
  
  
  METHODS
  Patients with inoperable or metastatic urothelial carcinoma; adequate bone marrow, renal, liver, and cardiac function; and Eastern Cooperative Oncology Group performance status < or = 2 were randomly assigned to receive MVAC at standard doses or docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) support.
  
  
  RESULTS
  Two hundred twenty patients were randomly assigned (MVAC, 109 patients; DC, 111 patients). Treatment with MVAC resulted in superior RR (54.2% v 37.4%; P =.017), median time to progression (TTP; 9.4 v 6.1 months; P =.003) and median survival (14.2 v 9.3 months; P =.026). After adjusting for prognostic factors, difference in TTP remained significant (hazard ratio [HR], 1.61; P =.005), whereas survival difference was nonsignificant at the 5% level (HR, 1.31; P =.089). MVAC caused more frequent grade 3 or 4 neutropenia (35.4% v 19.2%; P =.006), thrombocytopenia (5.7% v 0.9%; P =.046), and neutropenic sepsis (11.6% v 3.8%; P =.001). Toxicity of MVAC was considerably lower than that previously reported for MVAC administered without G-CSF.
  
  
  CONCLUSIONS
  MVAC is more effective than DC in advanced urothelial cancer. G-CSF-supported MVAC is well tolerated and could be used instead of classic MVAC as first-line treatment in advanced urothelial carcinoma.
authors.affiliation: Department of Clinical Therapeutics Urology, Hygiene and Epidemiology, University of Athens School of Medicine, Athens, Greece. abamias@med.uoa.gr
authors.forename: A
authors.initials: A
authors.lastname: Bamias
authors.forename: G
authors.initials: G
authors.lastname: Aravantinos
authors.forename: C
authors.initials: C
authors.lastname: Deliveliotis
authors.forename: D
authors.initials: D
authors.lastname: Bafaloukos
authors.forename: C
authors.initials: C
authors.lastname: Kalofonos
authors.forename: N
authors.initials: N
authors.lastname: Xiros
authors.forename: A
authors.initials: A
authors.lastname: Zervas
authors.forename: D
authors.initials: D
authors.lastname: Mitropoulos
authors.forename: E
authors.initials: E
authors.lastname: Samantas
authors.forename: D
authors.initials: D
authors.lastname: Pectasides
authors.forename: P
authors.initials: P
authors.lastname: Papakostas
authors.forename: D
authors.initials: D
authors.lastname: Gika
authors.forename: C
authors.initials: C
authors.lastname: Kourousis
authors.forename: A
authors.initials: A
authors.lastname: Koutras
authors.forename: C
authors.initials: C
authors.lastname: Papadimitriou
authors.forename: C
authors.initials: C
authors.lastname: Bamias
authors.forename: P
authors.initials: P
authors.lastname: Kosmidis
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011379:Prognosis; D043823:Taxoids / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate