Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials

被引：427

作者：

Bohlius, Julia ^{[2
]}

Schmidlin, Kurt ^{[2
]}

Brillant, Corinne ^{[1
]}

Schwarzer, Guido ^{[3
]}

Trelle, Sven ^{[2
,4
]}

Seidenfeld, Jerome ^{[5
]}

Zwahlen, Marcel ^{[2
,4
]}

Clarke, Michael ^{[6
,7
]}

Weingart, Olaf ^{[1
]}

Kluge, Sabine ^{[1
]}

Piper, Margaret ^{[8
]}

Rades, Dirk ^{[9
]}

Steensma, David P. ^{[10
]}

Djulbegovic, Benjamin ^{[11
,12
,13
]}

Fey, Martin F. ^{[14
,15
]}

Ray-Coquard, Isabelle ^{[16
]}

Machtay, Mitchell ^{[17
]}

Moebus, Volker ^{[18
]}

Thomas, Gillian ^{[19
]}

Untch, Michael ^{[20
]}

Schumacher, Martin ^{[3
]}

Egger, Matthias ^{[2
]}

Engert, Andreas ^{[1
]}

机构：

[1] Univ Hosp Cologne, Dept Internal Med 1, Cochrane Haematol Malignancies Grp, Cologne, Germany

[2] Univ Bern, ISPM, Bern, Switzerland

[3] Univ Med Ctr Freiburg, Inst Med Biometry & Med Informat, Freiburg, Germany

[4] Univ Hosp Bern, Inselspital, CTU Bern, CH-3010 Bern, Switzerland

[5] Amer Soc Clin Oncol, Dept Canc Policy & Clin Affairs, Alexandria, VA USA

[6] Natl Inst Hlth Res, UK Cochrane Ctr, Oxford, England

[7] Trinity Coll Dublin, Sch Nursing & Midwifery, Dublin, Ireland

[8] Technol Evaluat Ctr, Blue Cross & Blue Shield Assoc, Chicago, IL USA

[9] Univ Hosp Lubeck, Dept Radiat Oncol, Lubeck, Germany

[10] Mayo Clin, Div Hematol, Rochester, MN USA

[11] Univ S Florida, Clin Translat Sci Inst, Ctr Evidence Based Med & Hlth Outcome Res, Tampa, FL USA

[12] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hematol, Tampa, FL 33612 USA

[13] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hlth Outcomes Behav, Tampa, FL 33612 USA

[14] Univ Bern, Inst Med Oncol, Bern, Switzerland

[15] Univ Bern, Inselspital, CH-3010 Bern, Switzerland

[16] Ctr Leon Berard, F-69373 Lyon, France

[17] Thomas Jefferson Univ Hosp, Radiat Therapy Oncol Grp, Philadelphia, PA 19107 USA

[18] Acad Hosp Frankfurt Main Hochst, Frankfurt, Germany

[19] Odette Sunnybrook Canc Ctr, Gynecol Oncol Grp US, Toronto, ON, Canada

[20] Helios Hosp Berlin Buch, Clin Gynaecol, Berlin, Germany

来源：

LANCET | 2009年 / 373卷 / 9674期

关键词：

QUALITY-OF-LIFE; PLATINUM-BASED CHEMOTHERAPY; CELL LUNG-CANCER; PLACEBO-CONTROLLED TRIAL; NON-HODGKINS-LYMPHOMA; WEEKLY EPOETIN-ALPHA; PHASE-III TRIAL; DOUBLE-BLIND; DARBEPOETIN-ALPHA; ANEMIC PATIENTS;

D O I：

10.1016/S0140-6736(09)60502-X

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Erythropoiesis-stimulating agents reduce anaemia in patients with cancer and could improve their quality of life, but these drugs might increase mortality. We therefore did a meta-analysis of randomised controlled trials in which these drugs plus red blood cell transfusions were compared with transfusion alone for prophylaxis or treatment of anaemia in patients with cancer. Methods Data for patients treated with epoetin alfa, epoetin beta, or darbepoetin alfa were obtained and analysed by independent statisticians using fixed-effects and random-effects meta-analysis. Analyses were by intention to treat. Primary endpoints were mortality during the active study period and overall survival during the longest available follow-up, irrespective of anticancer treatment, and in patients given chemotherapy. Tests for interactions were used to identify differences in effects of erythropoiesis-stimulating agents on mortality across prespecified subgroups. Findings Data from a total of 13 933 patients with cancer in 53 trials were analysed. 1530 patients died during the active study period and 4993 overall. Erythropoiesis-stimulating agents increased mortality during the active study period (combined hazard ratio [cHR] 1.17, 95% CI 1.06-1.30) and worsened overall survival (1.06, 1.00-1.12), with little heterogeneity between trials (I-2 0%, p=0.87 for mortality during the active study period, and I-2 7.1%, p=0.33 for overall survival). 10 441 patients on chemotherapy were enrolled in 38 trials. The cHR for mortality during the active study period was 1.10 (0.98-1.24), and 1.04 (0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients given different anticancer treatments (p for interaction=0.42). Interpretation Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival. The increased risk of death associated with treatment with these drugs should be balanced against their benefits.

引用

页码：1532 / 1542

页数：11

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