cochrane epo vs darb in cancer

8/2/2019 Cochrane EPO vs DARB in Cancer

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Erythropoietin or Darbepoetin for patients with cancer -

meta-analysis based on individual patient data (Review)

Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke

MJ, Weingart O, Kluge S, Piper M, Napoli M, Rades D, Steensma D, Djulbegovic B, Fey MF,

Ray-Coquard I, Moebus V, Thomas G, Untch M, Schumacher M, Egger M, Engert A

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library

2010, Issue 11

http://www.thecochranelibrary.com

Erythropoietin or Darbepoetin for patients with cancer - meta-analysis based on individual patient data (Review)

Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
http://www.thecochranelibrary.com/http://www.thecochranelibrary.com/


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[Intervention Review]

Erythropoietin or Darbepoetin for patients with cancer -meta-analysis based on individual patient data

Julia Bohlius1, Kurt Schmidlin1, Corinne Brillant2, Guido Schwarzer3, Sven Trelle1, Jerome Seidenfeld4, Marcel Zwahlen1, Mike J

Clarke5, Olaf Weingart2, Sabine Kluge2, Margaret Piper6, Maryann Napoli7, Dirk Rades8, David Steensma9, Benjamin Djulbegovic10, Martin F Fey11, Isabelle Ray-Coquard12, Volker Moebus13 , Gillian Thomas14, Michael Untch15, Martin Schumacher16, Matthias

Egger17, Andreas Engert2

1Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. 2Cochrane Haematological Malignancies Group,

Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany. 3German Cochrane Centre, Insitute of

Medical Biometry and Medical Informatics, Freiburg, Germany. 4Department of Cancer Policy and Clinical Affairs, American Society

of Clinical Oncology, Alexandria, VA, USA. 5UK Cochrane Centre, Oxford, UK. 6Technology Evaluation Center, Blue Cross and

Blue Shield Association, Chicago, IL, USA. 7Center for Medical Consumers, New York, USA. 8Department of Radiation Oncology,

University Hospital, Lbeck, Germany. 9Mayo Clinic, Rochester, MN, USA. 10Professor of Medicine and Oncology, H. Lee Moffitt

Cancer Center, Center for Evidence Based Medicine and Health Outcomes Research, University of South Florida, Tampa, Florida,

USA. 11Department of Medical Oncology, University and Inselspital Bern, Bern, Switzerland. 12Centre Lon Brard, Lyon, France.13Department of Gynecology, Academic Hospital Frankfurt am Main Hchst, Frankfurt a.M., Germany. 14Odette Sunnybrook Cancer

Centre, University of Toronto, Toronto, Canada. 15Clinic for Gynaecology, Helios Hospital Berlin-Buch, Berlin, Germany. 16German

Cochrane Center, Institute of Medical Biometry and Medical Informatics, University Medical Center Freiburg, Freiburg, Germany.17Institute of Social Medicine, Institute of Social and Preventive Medicine, Bern, Switzerland

Contact address: Julia Bohlius, Institute of Social and Preventive Medicine, University of Bern, Bern, 3012, Switzerland.

[email protected]. [email protected].

Editorial group: Cochrane Haematological Malignancies Group.Publication status and date: Edited (no change to conclusions), published in Issue 11, 2010.

Review content assessed as up-to-date: 11 May 2009.

Citation: Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke MJ, Weingart O, Kluge S,

Piper M, Napoli M, Rades D, Steensma D, Djulbegovic B, Fey MF, Ray-Coquard I, Moebus V, Thomas G, Untch M, Schumacher M,

Egger M, Engert A. Erythropoietin or Darbepoetin for patients with cancer - meta-analysis based on individual patient data. Cochrane

Database of Systematic Reviews2009, Issue 3. Art. No.: CD007303. DOI: 10.1002/14651858.CD007303.pub2.


A B S T R A C T

Background

Erythropoiesis-stimulating agents (ESAs) reduce anemia in cancer patients and may improve quality of life, but there are concerns that

ESAs might increase mortality.

Objectives

Ourobjectives were to examine theeffect of ESAs andidentifyfactors that modify the effects of ESAs on overall survival, progression free

survival, thromboembolic and cardiovascular events as well as need for transfusions and other important safety and efficacy outcomes

in cancer patients.

Search strategy

We searched the Cochrane Library, Medline, Embase and conference proceedings for eligible trials. Manufacturers of ESAs were

contacted to identify additional trials.


mailto:[email protected]:[email protected]:[email protected]:[email protected]


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Selection criteria

We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusions (as necessary) versus red

blood cell transfusions (as necessary) alone, to prevent or treat anemia in adult or pediatric cancer patients with or without concurrent

antineoplastic therapy.

Data collection and analysis

We performed a meta-analysis of randomized controlled trials comparing epoetin alpha, epoetin beta or darbepoetin alpha plus red

blood cell transfusions versus transfusion alone, for prophylaxis or therapy of anemia while or after receiving anti-cancer treatment.

Patient-leveldata were obtained and analyzed by independent statisticians at two academic departments, using fixed-effects and random-

effects meta-analysis. Analyseswere according to the intention-to-treat principle. Primary endpoints were on study mortality and overall

survival during the longest available follow-up, regardless of anticancer treatment, and in patients receiving chemotherapy. Tests for

interactions were used to identify differences in effects of ESAs on mortality across pre-specified subgroups. The present review reports

only the results for the primary endpoint.

Main results

A total of 13933 cancer patients from 53 trials were analyzed, 1530 patients died on-study and 4993 overall. ESAs increased on study

mortality (combined hazard ratio [cHR] 1.17; 95% CI 1.06-1.30) and worsened overall survival (cHR 1.06; 95% CI 1.00-1.12),

with little heterogeneity between trials (I2 0%, p=0.87 and I2 7.1%, p=0.33, respectively). Thirty-eight trials enrolled 10441 patients

receiving chemotherapy. The cHR for on study mortality was 1.10 (95% CI 0.98-1.24) and 1.04; 95% CI 0.97-1.11) for overall

survival. There was little evidence for a difference between trials of patients receiving different cancer treatments (P for interaction=

0.42).

Authors conclusions

ESA treatment in cancer patients increased on study mortality and worsened overall survival. For patients undergoing chemotherapy

the increase was less pronounced, but an adverse effect could not be excluded.

P L A I N L A N G U A G E S U M M A R Y

Anti-anemia drugs shorten survival for some cancer patients

People with cancer may develop a blood problem called anemia, due to the treatment or from the disease itself. They will have very

low levels of healthy red blood cells, causing additional health problems. For years, doctors have tried to prevent or treat anemia with

injections of erythropoiesis stimulating agents (ESAs) in order to spare cancer patients the many serious harms associated with a red-

blood cell transfusion (such as hepatitis, transfusion-related acute lung injury, infection). Earlier reviews of the research showed that

ESA treatment reduces the need for transfusion but, in recent years, several studies have shown that ESAs themselves cause harm.

The drug may, for example, stimulate tumor growth and cause potentially fatal blood clots. In 2007, new studies reported that ESAs

shortens survival in people with breast, non-small cell lung, head and neck, lymphoid and cervical cancers.

A new systematic review was needed to evaluate the old and the new evidence together and determine the impact of ESAs on survival

in cancer patients to see if there are groups of patients who are at increased or decreased risk compared to the average. To accomplishthis the authors of this meta-analysis conducted an in-depth assessment of the individual patient data generated by the care of nearly

14,000 patients from 53 trials conducted worldwide. Data on each of these patients were provided by three companies that make

ESAs: Amgen, Johnson & Johnson, and Roche, and by several independent researchers. (The drug companies, however, had no role in

conducting the meta-analysis.) The trials investigated one of two types of ESAs, epoetin or darbepoetin, and compared the use of one

of these drugs plus red blood cell transfusion (as needed), with red blood cell transfusion alone (as needed). Most patients were given

their treatment while undergoing anti-cancer therapy (chemotherapy and/or radiotherapy); but others received the treatment after they

had completed their anti-cancer therapy. Some patients already had anemia; others were treated in order to prevent it. The patients had

many different forms of cancer and many different anti-cancer treatments.

The authors of this new meta-analysis concluded that ESA treatment shortens survival. They could not identify with certainty any

subgroup of patients at either increased or decreased risk of dying when taking ESAs. With their doctors help, cancer patients should

consider the risks of taking ESA against the risks of a blood transfusion. Be aware, however, that uncertainties remain about the

magnitude of each.




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cochrane epo vs darb in cancer

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