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
H. Von Der Maase et al., 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, J CL ONCOL, 18(17), 2000, pp. 3068-3077
Purpose: Gemcitabine plus cisplatin (OC) and methotrexate, vinblastine, dox
orubicin, and cisplatin (MVAC) were compared in patients with locally advan
ced or metastatic transitional-cell carcinoma (TCC) of the urothelium.
Patients and Methods: Patients with stage IV TCC and no prior systemic chem
otherapy were randomized to OC (gemcitabine 1,000 mg/m(2) days 1, 8, and 15
; cisplatin 70 mg/m(2) 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. Ov
erall survival was similar on both arms (hazards ratio [HR], 1.04; 95% conf
idence interval [CI], 0.82 to 1.32; P =.75), as were time to progressive di
sease (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 OC pa
tients completed six cycles of therapy, with fewer dose adjustments. The to
xic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MV
AC patients had grade 3/4 anemia (27% v 18%, respectively) and thrombocytop
enia (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 war 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 alapecia (55% v 11%,
respectively). Quality of life was maintained during treatment on both arm
s; however, more patients on GC fared better regarding weight, performance
status, and fatigue.
Conclusion: GC provides a similar survival advantage to MVAC with a better
safety profile and tolerability. This better-risk benefit ratio should chan
ge the standard of care for patients with locally advanced and metastatic T
CC from MVAC to OC. (C) 2000 by American Society of Clinical Oncology.