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Cochrane Database of Systematic Reviews

Routine versus selective antifungal administration for control of fungal infections in patients with cancer

Información

DOI:
https://doi.org/10.1002/14651858.CD000026.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 04 septiembre 2014see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Cáncer ginecológico, neurooncología y otros cánceres

Copyright:
  1. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

  • Peter C Gøtzsche

    Correspondencia a: Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark

    [email protected]

  • Helle Krogh Johansen

    The Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark

Contributions of authors

PCG wrote the protocol and the draft manuscript, did the searches and performed the statistical analyses. Both authors read the papers and extracted the data independently. HKJ commented on the various versions of the draft.

Sources of support

Internal sources

  • Rigshospitalet, Copenhagen, Denmark.

External sources

  • No sources of support supplied

Declarations of interest

Peter C Gøtzsche ‐ nothing to declare
Helle Krogh Johansennothing ‐ nothing to declare

Acknowledgements

We are grateful to the following investigators for having provided additional information on their trials: Dr Ellen Benhamou, Dr Hans Brincker, Dr Masataka Fukuda, Dr Jesse L Goodman, Dr Richard M Hansen, Dr Wolfgang Kern, Dr Marcio Nucci, Dr Jan Palmblad, Dr Andrew T Pavia, Dr John R Perfect, Professor Philip A Pizzo, Dr Ben E de Pauw, Dr Andreas Schaffner, Professor Gérard Schaison, Dr Jan Tollemar, Professor John R Wingard, and Dr Drew J Winston. We are grateful for the translation of the Japanese articles provided by Dr Hiroto Takada. We thank Bristol‐Myers Squibb and Janssen‐Cilag for supplementary literature searches. Finally, we thank Dr Hans Brincker for a useful discussion and Professor Peter Skinhøj for comments on the first published version of this meta‐analysis.

The National Institute for Health Research (NIHR) is the largest single funder of the Cochrane Gynaecological, Neuro‐oncology, Orphan Cancer Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.

Version history

Published

Title

Stage

Authors

Version

2014 Sep 04

Routine versus selective antifungal administration for control of fungal infections in patients with cancer

Review

Peter C Gøtzsche, Helle Krogh Johansen

https://doi.org/10.1002/14651858.CD000026.pub2

2002 Apr 22

Routine versus selective antifungal administration for control of fungal infections in patients with cancer

Review

Peter C Gøtzsche, Helle Krogh Johansen

https://doi.org/10.1002/14651858.CD000026

Differences between protocol and review

We have not recorded dropouts due to toxicity as they were reported rarely and inconsistently. We have added harms and also death ascribed to fungal infection as our research has shown that this outcome is reliable (Due 2006), contrary to our expectations.

Keywords

MeSH

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Comparison 1 Antifungals versus placebo or no treatment, Outcome 1 Death.
Figuras y tablas -
Analysis 1.1

Comparison 1 Antifungals versus placebo or no treatment, Outcome 1 Death.

Comparison 1 Antifungals versus placebo or no treatment, Outcome 2 Death related to fungal infection.
Figuras y tablas -
Analysis 1.2

Comparison 1 Antifungals versus placebo or no treatment, Outcome 2 Death related to fungal infection.

Comparison 1 Antifungals versus placebo or no treatment, Outcome 3 Invasive infections.
Figuras y tablas -
Analysis 1.3

Comparison 1 Antifungals versus placebo or no treatment, Outcome 3 Invasive infections.

Comparison 1 Antifungals versus placebo or no treatment, Outcome 4 Colonisation.
Figuras y tablas -
Analysis 1.4

Comparison 1 Antifungals versus placebo or no treatment, Outcome 4 Colonisation.

Comparison 1 Antifungals versus placebo or no treatment, Outcome 5 Use of escape drug.
Figuras y tablas -
Analysis 1.5

Comparison 1 Antifungals versus placebo or no treatment, Outcome 5 Use of escape drug.

Table 1. Harms

Trial

Trial drug

Number of patients

Harms

EORTC 1989

amphotericin B

80 versus 77

Treatment discontinuations: 6 pts on trial drug (infusion‐related toxicity, allergic reactions); Nephrotoxicity: 8 versus 3, none required dialysis and renal function restored later; Hypokalaemia: 33 versus 16

Goldstone 1994

amphotericin B

64 versus 69

Treatment discontinuations: 4 on trial drug (chills, rigour, hypotension, rash and bronchospasm); Elevated liver function tests: 26 versus 32; Nephrotoxicity: 1 on trial drug that did not require withdrawal of therapy

Kelsey 1999

amphotericin B

74 versus 87

Treatment discontinuations: 5 on trial drug, 1 on placebo because of immediate reactions; Nephrotoxicity: 9 versus 6; Hypokalaemia: 1 versus 0; Clinical adverse events were very similar in the two groups

Penack 2006.

amphotericin B

75 versus 57

Treatment discontinuations: 2 (1 skin rash, 1 chills) versus 0; Other harms: "no differences in ... liver function tests, renal function parameters and hypokalaemia"

Perfect 1992

amphotericin B

91 versus 91

More infusion‐related harms on active drug, but no data provided; No significant differences in renal function, hepatic enzymes or electrolytes (no data provided)

Pizzo 1982

amphotericin B

18 versus 16

Treatment discontinuations: none; Rash: 2 versus 1; Azotaemia: 1 versus 0; liver enzyme elevations: 2 versus 3; Electrolyte abnormalities: 18 versus 16

Riley 1994

amphotericin B

17 versus 18

Treatment discontinuations: none; Renal function: no difference (P value 0.82 for blood urea, P value 0.63 for creatinine); Potassium supplements: no difference; Infusion reactions: none

Suda 1980

amphotericin B

39 versus 31

Article is in Japanese

Tollemar 1993

amphotericin B

42 versus 42

Treatment discontinuations: 4 versus 0 for infusion reactions; Potassium supplementation: no difference; Renal function: no useful data, but only small changes reported, compared to normal ranges

Fukuda 1994

fluconazole

37 versus 26

Article is in Japanese

Goodman 1992

fluconazole

179 versus 177

Treatment discontinuations: 1 on trial drug, 2 on placebo for clinical side effects, and 17 versus 11 for elevated liver function tests; in 7 versus 3, hepatic dysfunction contributed to death; Graft‐versus‐host disease or organ failure: 44 versus 24 deaths; Nausea: 13 versus 9; Skin rash: 9 versus 9; Eosinophilia in 6 versus 0

Kern 1998

fluconazole

36 versus 32

Bacteriaemia: 15 versus 7; Other harms similar: 5 versus 6 elevations in transaminases, 19 versus 17 nausea or vomiting, 3 versus 0 allergy

Rotstein 1999

fluconazole

141 versus 133

Treatment discontinuations: none reported; Elevated liver enzymes: 17 versus 19; Rash: 51 versus 59; Nausea: 106 versus 95; Vomiting: 68 versus 85

Schaffner 1995

fluconazole

76 versus 76 episodes

Treatment discontinuations: none reported; No data on harms ("no significant differences were found")

Slavin 1995

fluconazole

152 versus 148

Treatment discontinuations: 32 versus 31 for abnormal liver function; Graft‐versus‐host disease: 102 versus 85; Nausea: 33 versus 22; Seizures: 8 versus 9; Liver enzymes: no differences

Winston 1993

fluconazole

124 versus 133

Treatment discontinuations: none reported; Elevated liver enzymes: 25 versus 14; Nausea and vomiting: 9 versus 5; Rash: 13 versus 7; Other harms were similarly distributed

Yamac 1995

fluconazole

41 versus 29

Treatment discontinuations: none reported; Other harms: no data

Acuna 1981

ketoconazole

28 versus 24

No data

Benhamou 1991

ketoconazole

63 versus 62

Treatment discontinuations: 38 versus 14 (among them 2 patients with veno‐occlusive disease, 1 hepatitis, 3 skin rash in active group; none in placebo group); Severe gastrointestinal intolerance: 4 versus 7; Three‐fold greater values than normal for transaminases: 13 versus 8

Brincker 1983

ketoconazole

19 versus 19

One patient on trial drug stopped treatment because of universal exanthema

Estey 1984

ketoconazole

77 versus 73

Bacterial infections: 33 versus 24

Hansen 1987

ketoconazole

27 versus 29

Treatment discontinuations: 2 on trial drug (1 skin rash and 1 elevated liver function tests); Bacterial infections: 20% versus 15% of neutropenic episodes

Hughes 1983

ketoconazole

42 versus 22

Treatment discontinuations:1 on trial drug (nausea and anorexia); Other harms: 2 nausea and anorexia, 1 abdominal pain, 1 transient rash, all on trial drug

Palmblad 1992

ketoconazole

55 versus 61

Treatment discontinuations: 2 (elevated transaminases) versus 6 (1 elevated transaminases, 5 exanthema); Bacteriaemias: 37 versus 21

Siegel 1982a

ketoconazole

12 versus 13

No data

Brincker 1978

miconazole

15 versus 15

None ascribable to trial drug

Wingard 1987

miconazole

97 versus 111

Treatment discontinuations: 1 (pruritis and flushing) versus 2 (1 rash, 1 nausea); Severe hypotension: 2 on trial drug

Caselli 1990

itraconazole, amphotericin B, ketoconazole

30 versus 10

No data

Kaptan 2003

itraconazole

31 versus 24

Treatment discontinuations: 2 on trial drug (cardiac arrhytmia and gastric irritation); "there was a clinical impression that hypokalaemia occurred at a greater rate in patients with itraconazole"

Menichetti 1999

itraconazole

201 versus 204

Treatment discontinuations: 37 versus 27; Bacteriaemia: 47 versus 31; Elevated transaminases: 5 versus 3

Nucci 2000

itraconazole

104 versus 106

Treatment discontinuations: 3 versus 4; Skin rash: 3 versus 1; Elevated liver enzymes: 3 versus 4; Nausea: 2 on placebo

Vreugdenhil 1993

itraconazole

49 versus 49

Treatment discontinuations: 1 (nausea) versus 1 (liver function deterioration); Liver function deterioration: 28 versus 22 episodes; Renal function deterioration: 4 versus 2 episodes

Figuras y tablas -
Table 1. Harms
Comparison 1. Antifungals versus placebo or no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Death Show forest plot

26

3902

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.81, 1.09]

1.1 Amphotericin

9

988

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.50, 0.96]

1.2 Fluconazole

7

1470

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.84, 1.30]

1.3 Ketoconazole

4

429

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.63, 1.49]

1.4 Miconazole

2

238

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.71, 1.87]

1.5 Itraconazole

4

777

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.63, 1.40]

2 Death related to fungal infection Show forest plot

23

3490

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.38, 0.71]

2.1 Amphotericin

9

988

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.26, 0.76]

2.2 Fluconazole

6

1213

Risk Ratio (M‐H, Fixed, 95% CI)

0.42 [0.24, 0.73]

2.3 Ketoconazole

3

304

Risk Ratio (M‐H, Fixed, 95% CI)

1.49 [0.55, 4.04]

2.4 Miconazole

1

208

Risk Ratio (M‐H, Fixed, 95% CI)

0.13 [0.01, 2.33]

2.5 Itraconazole

4

777

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.31, 1.56]

3 Invasive infections Show forest plot

30

4044

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.39, 0.64]

3.1 Amphotericin

8

855

Risk Ratio (M‐H, Fixed, 95% CI)

0.41 [0.24, 0.73]

3.2 Fluconazole

8

1539

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.27, 0.57]

3.3 Ketoconazole

7

562

Risk Ratio (M‐H, Fixed, 95% CI)

1.32 [0.68, 2.54]

3.4 Miconazole

2

238

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.20, 1.31]

3.5 Itraconazole

4

810

Risk Ratio (M‐H, Fixed, 95% CI)

0.53 [0.29, 0.97]

3.6 Itraconazole/ketoconazole/amphotericin

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Colonisation Show forest plot

22

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 Amphotericin

3

378

Risk Ratio (M‐H, Random, 95% CI)

0.51 [0.33, 0.77]

4.2 Fluconazole

6

1393

Risk Ratio (M‐H, Random, 95% CI)

0.55 [0.33, 0.90]

4.3 Ketoconazole

8

626

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.51, 0.87]

4.4 Miconazole

2

238

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.37, 2.24]

4.5 Itraconazole

2

503

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.57, 1.45]

4.6 Itraconazole/ketoconazole/amphotericin

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.57 [0.31, 1.04]

5 Use of escape drug Show forest plot

24

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Amphotericin

6

636

Risk Ratio (M‐H, Random, 95% CI)

0.60 [0.35, 1.03]

5.2 Fluconazole

7

1469

Risk Ratio (M‐H, Random, 95% CI)

0.88 [0.76, 1.02]

5.3 Ketoconazole

6

412

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.58, 1.44]

5.4 Miconazole

2

238

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.94, 1.46]

5.5 Itraconazole

3

712

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.57, 0.95]

Figuras y tablas -
Comparison 1. Antifungals versus placebo or no treatment