title: Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study.
abstract: OBJECTIVE
  Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium.
  
  
  METHODS
  Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m2 days 1, 8 and 15; cisplatin 70 mg/m2 day 2) or standard MVAC every 28 days for a maximum of six cycles.
  
  
  RESULTS
  Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio [HR], 1.04; 95% confidence interval [CI], 0.82 to 1.32; P = .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively), and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alopecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue.
  
  
  CONCLUSIONS
  GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.
authors.affiliation: Aarhus University Hospital, Denmark. hvdm@oncology.dk
authors.forename: H
authors.initials: H
authors.lastname: von der Maase
authors.forename: S W
authors.initials: SW
authors.lastname: Hansen
authors.forename: J T
authors.initials: JT
authors.lastname: Roberts
authors.forename: L
authors.initials: L
authors.lastname: Dogliotti
authors.forename: T
authors.initials: T
authors.lastname: Oliver
authors.forename: M J
authors.initials: MJ
authors.lastname: Moore
authors.forename: I
authors.initials: I
authors.lastname: Bodrogi
authors.forename: P
authors.initials: P
authors.lastname: Albers
authors.forename: A
authors.initials: A
authors.lastname: Knuth
authors.forename: C M
authors.initials: CM
authors.lastname: Lippert
authors.forename: P
authors.initials: P
authors.lastname: Kerbrat
authors.forename: P
authors.initials: P
authors.lastname: Sanchez Rovira
authors.forename: P
authors.initials: P
authors.lastname: Wersall
authors.forename: S P
authors.initials: SP
authors.lastname: Cleall
authors.forename: D F
authors.initials: DF
authors.lastname: Roychowdhury
authors.forename: I
authors.initials: I
authors.lastname: Tomlin
authors.forename: C M
authors.initials: CM
authors.lastname: Visseren-Grul
authors.forename: P F
authors.initials: PF
authors.lastname: Conte
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006760:Hospitalization; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011788:Quality of Life; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: D000890:Anti-Infective Agents; D003841:Deoxycytidine; D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin; D008727:Methotrexate; D000093542:Gemcitabine