Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial

被引:73
作者
Gore, Martin E. [1 ]
Griffin, Clare L. [2 ]
Hancock, Barry [3 ]
Patel, Poulam M. [4 ]
Pyle, Lynda
Aitchison, Michael [5 ]
James, Nicholas [6 ]
Oliver, Roderick T. D. [7 ]
Mardiak, Jozef [8 ]
Hussain, Tahera [2 ]
Sylvester, Richard [9 ]
Parmar, Mahesh K. B. [2 ]
Royston, Patrick [2 ]
Mulders, Peter F. A. [10 ]
机构
[1] Royal Marsden Hosp NHS Trust, Dept Med, London SW3 6JJ, England
[2] MRC, Clin Trials Unit, London, England
[3] Weston Pk Hosp, Sheffield, S Yorkshire, England
[4] Univ Nottingham, Nottingham NG7 2RD, England
[5] Western Infirm & Associated Hosp, Beatson Oncol Ctr, Glasgow G11 6NT, Lanark, Scotland
[6] Univ Birmingham, Canc Res UK Inst Canc Studies, Birmingham, W Midlands, England
[7] QMUL, Barts & London Med Sch, Inst Canc, London, England
[8] Natl Canc Inst, Bratislava, Slovakia
[9] European Org Res & Treatment Canc Headquarters, Brussels, Belgium
[10] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands
关键词
DOSE RECOMBINANT INTERLEUKIN-2; CLINICAL-TRIALS; SURVIVAL; MEDROXYPROGESTERONE; VINBLASTINE; SUNITINIB; CANCER;
D O I
10.1016/S0140-6736(09)61921-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background In metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a. Methods RE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965. Findings 502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37.2 months (24.8-52.3). Median overall survival was 18.8 months (17.0-23.2) for patients receiving interferon alfa-2a versus 18.6 months (16.5-20.6) for those receiving combination therapy. overall survival did not differ between the two groups (hazard ratio 1.05 [95% Cl 0.90-1.21], p=0.55; absolute difference 0.3% (-5.1. to 5.6) at 1 year and 2.7% (-8.2 to 2.9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment. Interpretation Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce remissions that are of clinically relevant length in some patients. identification of patients who will benefit from immunotherapy is crucial.
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收藏
页码:641 / 648
页数:8
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