Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: EORTC Study 30986

被引:547
作者
De Santis, Maria [1 ,2 ,3 ]
Bellmunt, Joaquim [4 ,5 ,6 ]
Mead, Graham [7 ]
Kerst, J. Martijn [9 ]
Leahy, Michael [8 ]
Maroto, Pablo
Gil, Thierry
Marreaud, Sandrine
Daugaard, Gedske [13 ]
Skoneczna, Iwona [12 ]
Collette, Sandra [11 ]
Lorent, Julie [11 ]
de Wit, Ronald [10 ]
Sylvester, Richard [11 ]
机构
[1] Kaiser Franz Josef Hosp, A-1100 Vienna, Austria
[2] Appl Canc Research Inst Translat Res Vienna, Cent European Anticanc Drug Dev Platform, Vienna, Austria
[3] Ludwig Boltzmann Inst Appl Canc Res Vienna Cluste, Vienna, Austria
[4] Hosp Gen Valle Hebron, Barcelona, Spain
[5] Mar LInstitMunicipal Invest Med, Barcelona, Spain
[6] Univ Hosp San Pablo, Barcelona, Spain
[7] Southampton Gen Hosp, Southampton, England
[8] St James Univ Hosp, Leeds, W Yorkshire, England
[9] Netherlands Canc Inst, Amsterdam, Netherlands
[10] Erasmus Univ, Med Ctr, Rotterdam, Netherlands
[11] European Org Res & Treatment Canc Headquarters, Brussels, Belgium
[12] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland
[13] Rigshosp, DK-2100 Copenhagen, Denmark
关键词
TRANSITIONAL-CELL CARCINOMA; COMPREHENSIVE GERIATRIC ASSESSMENT; GEMCITABINE PLUS CISPLATIN; ADVANCED BLADDER-CARCINOMA; SINGLE-AGENT GEMCITABINE; LONG-TERM-SURVIVAL; CREATININE CLEARANCE; PROGNOSTIC-FACTORS; ONCOLOGY SIOG; III TRIAL;
D O I
10.1200/JCO.2011.37.3571
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy. Patients and Methods The primary objective of the phase III part of this study was to compare the overall survival (OS) of chemotherapy-naive patients with measurable disease and an impaired renal function (glomerular filtration rate < 60 but > 30 mL/min) and/or performance score of 2 who were randomly assigned to receive either gemcitabine/carboplatin (GC) or methotrexate/carboplatin/vinblastine (M-CAVI). To detect an increase of 50% in median survival with GC compared with M-CAVI (13.5 v 9 months) based on a two-sided log-rank test at error rates alpha = .05 and beta = .20, 225 patients were required. Secondary end points were overall response rate (ORR), progression-free survival (PFS), toxicity, and quality of life. Results In all, 238 patients were randomly assigned by 29 institutions over a period of 7 years. The median follow-up was 4.5 years. Best ORRs were 41.2% (36.1% confirmed response) for patients receiving GC versus 30.3% (21.0% confirmed response) for patients receiving M-CAVI (P = .08). Median OS was 9.3 months in the GC arm and 8.1 months in the M-CAVI arm (P = .64). There was no difference in PFS (P = .78) between the two arms. Severe acute toxicity (death, grade 4 thrombocytopenia with bleeding, grade 3 or 4 renal toxicity, neutropenic fever, or mucositis) was observed in 9.3% of patients receiving GC and 21.2% of patients receiving M-CAVI. Conclusion There were no significant differences in efficacy between the two treatment groups. The incidence of severe acute toxicities was higher for those receiving M-CAVI. J Clin Oncol 30:191-199. (C) 2011 by American Society of Clinical Oncology
引用
收藏
页码:191 / 199
页数:9
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