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, S. W. Hansen, J. T. Roberts, L. Dogliotti, T. Oliver, M. J. Moore, I. Bodrogi, P. Albers, A. Knuth, C. M. Lippert, P. Kerbrat, P. Sanchez Rovira, P. Wersall, S. P. Cleall, D. F. Roychowdhury, I. Tomlin, C. M. Visseren-Grul, P. F. Conte

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Abstract

Purpose: 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. Patients and 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. Conclusion: 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. (C) 2000 by American Society of Clinical Oncology.

Original languageEnglish
Pages (from-to)3068-3077
Number of pages10
JournalJournal of Clinical Oncology
Volume18
Issue number17
Publication statusPublished - 2000

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gemcitabine
Vinblastine
Urinary Bladder Neoplasms
Methotrexate
Doxorubicin
Cisplatin
Transitional Cell Carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Von der Maase, H.; Hansen, S. W.; Roberts, J. T.; Dogliotti, L.; Oliver, T.; Moore, M. J.; Bodrogi, I.; Albers, P.; Knuth, A.; Lippert, C. M.; Kerbrat, P.; Sanchez Rovira, P.; Wersall, P.; Cleall, S. P.; Roychowdhury, D. F.; Tomlin, I.; Visseren-Grul, C. M.; Conte, P. F.

In: Journal of Clinical Oncology, Vol. 18, No. 17, 2000, p. 3068-3077.

Research output: Contribution to journalArticle

Von der Maase, H, Hansen, SW, Roberts, JT, Dogliotti, L, Oliver, T, Moore, MJ, Bodrogi, I, Albers, P, Knuth, A, Lippert, CM, Kerbrat, P, Sanchez Rovira, P, Wersall, P, Cleall, SP, Roychowdhury, DF, Tomlin, I, Visseren-Grul, CM & Conte, PF 2000, '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', Journal of Clinical Oncology, vol. 18, no. 17, pp. 3068-3077.
Von der Maase, H. ; Hansen, S. W. ; Roberts, J. T. ; Dogliotti, L. ; Oliver, T. ; Moore, M. J. ; Bodrogi, I. ; Albers, P. ; Knuth, A. ; Lippert, C. M. ; Kerbrat, P. ; Sanchez Rovira, P. ; Wersall, P. ; Cleall, S. P. ; Roychowdhury, D. F. ; Tomlin, I. ; Visseren-Grul, C. M. ; Conte, P. F. / 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. In: Journal of Clinical Oncology. 2000 ; Vol. 18, No. 17. pp. 3068-3077.
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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 = "Purpose: 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. Patients and 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. Conclusion: 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. (C) 2000 by American Society of Clinical Oncology.",
author = "{Von der Maase}, H. and Hansen, {S. W.} and Roberts, {J. T.} and L. Dogliotti and T. Oliver and Moore, {M. J.} and I. Bodrogi and P. Albers and A. Knuth and Lippert, {C. M.} and P. Kerbrat and {Sanchez Rovira}, P. and P. Wersall and Cleall, {S. P.} and Roychowdhury, {D. F.} and I. Tomlin and Visseren-Grul, {C. M.} and Conte, {P. F.}",
year = "2000",
language = "English",
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pages = "3068--3077",
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TY - JOUR

T1 - Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer

T2 - Results of a large, randomized, multinational, multicenter, phase III study

AU - Von der Maase, H.

AU - Hansen, S. W.

AU - Roberts, J. T.

AU - Dogliotti, L.

AU - Oliver, T.

AU - Moore, M. J.

AU - Bodrogi, I.

AU - Albers, P.

AU - Knuth, A.

AU - Lippert, C. M.

AU - Kerbrat, P.

AU - Sanchez Rovira, P.

AU - Wersall, P.

AU - Cleall, S. P.

AU - Roychowdhury, D. F.

AU - Tomlin, I.

AU - Visseren-Grul, C. M.

AU - Conte, P. F.

PY - 2000

Y1 - 2000

N2 - Purpose: 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. Patients and 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. Conclusion: 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. (C) 2000 by American Society of Clinical Oncology.

AB - Purpose: 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. Patients and 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. Conclusion: 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. (C) 2000 by American Society of Clinical Oncology.

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