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Cochrane Database of Systematic Reviews

Kombinirana naspram sekvencijske kemoterapije jednim lijekom za metastatski rak dojke

Información

DOI:
https://doi.org/10.1002/14651858.CD008792.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 18 diciembre 2013see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Cáncer de mama

Copyright:
  1. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

  • Rachel F Dear

    Correspondencia a: Sydney Medical School, The University of Sydney, Sydney, Australia

    [email protected]

    [email protected]

  • Kevin McGeechan

    Wiser Healthcare, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

  • Marisa C Jenkins

    Sydney School of Public Health, The University of Sydney, Sydney, Australia

  • Alexandra Barratt

    Wiser Healthcare, Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

  • Martin HN Tattersall

    Sydney Medical School, The University of Sydney, Sydney, Australia

  • Nicholas Wilcken

    Sydney Medical School, The University of Sydney, Sydney, Australia

    Medical Oncology, Crown Princess Mary Cancer Centre, Westmead, Australia

Contributions of authors

Rachel Dear (RD), Martin Tattersall (MT) and Nicholas Wilcken (NW) conceived the study objective. RD wrote the review, which was reviewed and revised by MT, Alexandra Barratt (AB), NW, Kevin McGeechan (KMcG), and Marisa Jenkins (MJ).

Sources of support

Internal sources

  • Nil, Other

External sources

  • Nil, Other

Declarations of interest

None

Acknowledgements

We would like to thank Fergus Tai for his work identifying studies through the Cochrane Breast Cancer Group Specialised Register. We would also like to thank Melina Willson for her advice during the review process.

Version history

Published

Title

Stage

Authors

Version

2013 Dec 18

Combination versus sequential single agent chemotherapy for metastatic breast cancer

Review

Rachel F Dear, Kevin McGeechan, Marisa C Jenkins, Alexandra Barratt, Martin HN Tattersall, Nicholas Wilcken

https://doi.org/10.1002/14651858.CD008792.pub2

2010 Oct 06

Combination versus sequential single agent chemotherapy for metastatic breast cancer

Protocol

Rachel F Dear, Martin HN Tattersall, Kevin McGeechan, Alexandra Barratt, Nicholas Wilcken

https://doi.org/10.1002/14651858.CD008792

Differences between protocol and review

In the protocol we proposed only including first and second‐line chemotherapy trials. Our review includes a trial of third‐line chemotherapy (Park 2010, prior treatment with anthracyclines or taxanes) because the paper met all our other eligibility criteria.

A pre‐specified secondary outcome in the protocol was stable disease. We have not reported this outcome because overall tumour response rate (which includes complete response and partial response) is a more commonly reported outcome that can then be compared to other similar reviews on this topic.

Another pre‐specified outcome in the protocol was "QTWIST" (quality‐adjusted time without symptoms of disease and toxicity). We have not reported this in our review because this outcome was not reported in any of the trials included in this review, and toxicity data were not consistently reported so that time with side effects from chemotherapy could not accurately be extracted.

In the review, the 'Human' limit in the MEDLINE search strategy and the 'Randomised controlled trial' limit in the EMBASE search strategy were revised.

Notes

Two studies (Campone 2013; Zhang 2013) were categorised under the section 'Characteristics of studies awaiting classification' because the trials were completed but with insufficient data for inclusion at present. The results from these two small trials will be included in an updated version of this review.

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.

Results of search strategy applied 31 October 2013 for combination versus sequential single agent chemotherapy for metastatic breast cancer.

Figuras y tablas -
Figure 1

Results of search strategy applied 31 October 2013 for combination versus sequential single agent chemotherapy for metastatic breast cancer.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figuras y tablas -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Forest plot of comparison: 1 Overall survival, outcome: 1.1 Overall survival (all trials).

Figuras y tablas -
Figure 3

Forest plot of comparison: 1 Overall survival, outcome: 1.1 Overall survival (all trials).

Forest plot of comparison: 2 Progression‐free survival, outcome: 2.1 Progression‐free survival (amended analysis).

Figuras y tablas -
Figure 4

Forest plot of comparison: 2 Progression‐free survival, outcome: 2.1 Progression‐free survival (amended analysis).

Forest plot of comparison: 3 Overall response, outcome: 3.1 Overall response (all trials).

Figuras y tablas -
Figure 5

Forest plot of comparison: 3 Overall response, outcome: 3.1 Overall response (all trials).

Forest plot of comparison: 24 Overall response ‐ schema 1 versus schema 2, outcome: 24.1 Overall response ‐ schema 1 versus schema 2.

Figuras y tablas -
Figure 6

Forest plot of comparison: 24 Overall response ‐ schema 1 versus schema 2, outcome: 24.1 Overall response ‐ schema 1 versus schema 2.

Comparison 1: Overall survival, Outcome 1: Overall survival (all trials)

Figuras y tablas -
Analysis 1.1

Comparison 1: Overall survival, Outcome 1: Overall survival (all trials)

Comparison 2: Progression‐free survival, Outcome 1: Progression‐free survival (amended analysis)

Figuras y tablas -
Analysis 2.1

Comparison 2: Progression‐free survival, Outcome 1: Progression‐free survival (amended analysis)

Comparison 2: Progression‐free survival, Outcome 2: Progression‐free survival (all trials)

Figuras y tablas -
Analysis 2.2

Comparison 2: Progression‐free survival, Outcome 2: Progression‐free survival (all trials)

Comparison 3: Overall response, Outcome 1: Overall response (all trials)

Figuras y tablas -
Analysis 3.1

Comparison 3: Overall response, Outcome 1: Overall response (all trials)

Comparison 4: Treatment‐related deaths, Outcome 1: Treatment‐related deaths (all trials)

Figuras y tablas -
Analysis 4.1

Comparison 4: Treatment‐related deaths, Outcome 1: Treatment‐related deaths (all trials)

Comparison 5: Neutropenia, Outcome 1: Neutropaenia

Figuras y tablas -
Analysis 5.1

Comparison 5: Neutropenia, Outcome 1: Neutropaenia

Comparison 6: Febrile neutropenia, Outcome 1: Febrile neutropenia

Figuras y tablas -
Analysis 6.1

Comparison 6: Febrile neutropenia, Outcome 1: Febrile neutropenia

Comparison 7: Nausea and vomiting, Outcome 1: Nausea and vomiting

Figuras y tablas -
Analysis 7.1

Comparison 7: Nausea and vomiting, Outcome 1: Nausea and vomiting

Comparison 8: Overall survival ‐ risk of bias, Outcome 1: Overall survival ‐ risk of bias

Figuras y tablas -
Analysis 8.1

Comparison 8: Overall survival ‐ risk of bias, Outcome 1: Overall survival ‐ risk of bias

Comparison 9: Progression‐free survival ‐ risk of bias, Outcome 1: Progression‐free survival ‐ risk of bias (amended analysis)

Figuras y tablas -
Analysis 9.1

Comparison 9: Progression‐free survival ‐ risk of bias, Outcome 1: Progression‐free survival ‐ risk of bias (amended analysis)

Comparison 9: Progression‐free survival ‐ risk of bias, Outcome 2: Progression‐free survival ‐ risk of bias

Figuras y tablas -
Analysis 9.2

Comparison 9: Progression‐free survival ‐ risk of bias, Outcome 2: Progression‐free survival ‐ risk of bias

Comparison 10: Overall response ‐ risk of bias, Outcome 1: Overall response ‐ risk of bias

Figuras y tablas -
Analysis 10.1

Comparison 10: Overall response ‐ risk of bias, Outcome 1: Overall response ‐ risk of bias

Comparison 11: Treatment‐related deaths ‐ risk of bias, Outcome 1: Treatment‐related deaths ‐ risk of bias

Figuras y tablas -
Analysis 11.1

Comparison 11: Treatment‐related deaths ‐ risk of bias, Outcome 1: Treatment‐related deaths ‐ risk of bias

Comparison 12: Neutropenia ‐ risk of bias, Outcome 1: Neutropaenia ‐ risk of bias

Figuras y tablas -
Analysis 12.1

Comparison 12: Neutropenia ‐ risk of bias, Outcome 1: Neutropaenia ‐ risk of bias

Comparison 13: Febrile neutropenia ‐ risk of bias, Outcome 1: Febrile neutropenia ‐ risk of bias

Figuras y tablas -
Analysis 13.1

Comparison 13: Febrile neutropenia ‐ risk of bias, Outcome 1: Febrile neutropenia ‐ risk of bias

Comparison 14: Nausea and vomiting ‐ risk of bias, Outcome 1: Nausea and vomiting ‐ risk of bias

Figuras y tablas -
Analysis 14.1

Comparison 14: Nausea and vomiting ‐ risk of bias, Outcome 1: Nausea and vomiting ‐ risk of bias

Comparison 15: Overall survival ‐ line of chemotherapy, Outcome 1: Overall survival ‐ line of chemotherapy

Figuras y tablas -
Analysis 15.1

Comparison 15: Overall survival ‐ line of chemotherapy, Outcome 1: Overall survival ‐ line of chemotherapy

Comparison 16: Progression‐free survival ‐ line of chemotherapy, Outcome 1: Progression free survival ‐ line of chemotherapy (amended analysis)

Figuras y tablas -
Analysis 16.1

Comparison 16: Progression‐free survival ‐ line of chemotherapy, Outcome 1: Progression free survival ‐ line of chemotherapy (amended analysis)

Comparison 16: Progression‐free survival ‐ line of chemotherapy, Outcome 2: Progression free survival ‐ line of chemotherapy

Figuras y tablas -
Analysis 16.2

Comparison 16: Progression‐free survival ‐ line of chemotherapy, Outcome 2: Progression free survival ‐ line of chemotherapy

Comparison 17: Overall response ‐ line of chemotherapy, Outcome 1: Overall response ‐ subgroup analysis, line of chemotherapy

Figuras y tablas -
Analysis 17.1

Comparison 17: Overall response ‐ line of chemotherapy, Outcome 1: Overall response ‐ subgroup analysis, line of chemotherapy

Comparison 18: Treatment‐related deaths ‐ line of chemotherapy, Outcome 1: Treatment‐related deaths ‐ line of chemotherapy

Figuras y tablas -
Analysis 18.1

Comparison 18: Treatment‐related deaths ‐ line of chemotherapy, Outcome 1: Treatment‐related deaths ‐ line of chemotherapy

Comparison 19: Neutropenia ‐ line of chemotherapy, Outcome 1: Neutropaenia ‐ line of chemotherapy

Figuras y tablas -
Analysis 19.1

Comparison 19: Neutropenia ‐ line of chemotherapy, Outcome 1: Neutropaenia ‐ line of chemotherapy

Comparison 20: Febrile neutropenia ‐ line of chemotherapy, Outcome 1: Febrile neutropenia ‐ line of chemotherapy

Figuras y tablas -
Analysis 20.1

Comparison 20: Febrile neutropenia ‐ line of chemotherapy, Outcome 1: Febrile neutropenia ‐ line of chemotherapy

Comparison 21: Nausea and vomiting ‐ line of chemotherapy, Outcome 1: Nausea and vomiting ‐ line of chemotherapy

Figuras y tablas -
Analysis 21.1

Comparison 21: Nausea and vomiting ‐ line of chemotherapy, Outcome 1: Nausea and vomiting ‐ line of chemotherapy

Comparison 22: Overall survival ‐ schema 1 versus schema 2, Outcome 1: Overall survival ‐ Schema 1 versus Schema 2

Figuras y tablas -
Analysis 22.1

Comparison 22: Overall survival ‐ schema 1 versus schema 2, Outcome 1: Overall survival ‐ Schema 1 versus Schema 2

Comparison 23: Progression‐free survival ‐ schema 1 versus schema 2, Outcome 1: Progression‐free survival ‐ Schema 1 versus Schema 2 (amended analysis)

Figuras y tablas -
Analysis 23.1

Comparison 23: Progression‐free survival ‐ schema 1 versus schema 2, Outcome 1: Progression‐free survival ‐ Schema 1 versus Schema 2 (amended analysis)

Comparison 23: Progression‐free survival ‐ schema 1 versus schema 2, Outcome 2: Progression‐free survival ‐ Schema 1 versus Schema 2

Figuras y tablas -
Analysis 23.2

Comparison 23: Progression‐free survival ‐ schema 1 versus schema 2, Outcome 2: Progression‐free survival ‐ Schema 1 versus Schema 2

Comparison 24: Overall response ‐ schema 1 versus schema 2, Outcome 1: Overall response ‐ Schema 1 versus Schema 2

Figuras y tablas -
Analysis 24.1

Comparison 24: Overall response ‐ schema 1 versus schema 2, Outcome 1: Overall response ‐ Schema 1 versus Schema 2

Comparison 25: Treatment‐related deaths ‐ schema 1 versus schema 2, Outcome 1: Treatment‐related deaths ‐ Schema 1 versus Schema 2

Figuras y tablas -
Analysis 25.1

Comparison 25: Treatment‐related deaths ‐ schema 1 versus schema 2, Outcome 1: Treatment‐related deaths ‐ Schema 1 versus Schema 2

Comparison 26: Neutropenia ‐ schema 1 versus schema 2, Outcome 1: Neutropaenia ‐ subgroup analysis, Schema 1 versus Schema 2

Figuras y tablas -
Analysis 26.1

Comparison 26: Neutropenia ‐ schema 1 versus schema 2, Outcome 1: Neutropaenia ‐ subgroup analysis, Schema 1 versus Schema 2

Comparison 27: Febrile neutropenia ‐ schema 1 versus schema 2, Outcome 1: Febrile neutropenia ‐ Schema 1 versus Schema 2

Figuras y tablas -
Analysis 27.1

Comparison 27: Febrile neutropenia ‐ schema 1 versus schema 2, Outcome 1: Febrile neutropenia ‐ Schema 1 versus Schema 2

Comparison 28: Nausea and vomiting ‐ schema 1 versus schema 2, Outcome 1: Nausea and vomiting ‐ Schema 1 versus Schema 2

Figuras y tablas -
Analysis 28.1

Comparison 28: Nausea and vomiting ‐ schema 1 versus schema 2, Outcome 1: Nausea and vomiting ‐ Schema 1 versus Schema 2

Comparison 29: Overall survival ‐ relative dose intensity, Outcome 1: Overall survival ‐ relative dose intensity

Figuras y tablas -
Analysis 29.1

Comparison 29: Overall survival ‐ relative dose intensity, Outcome 1: Overall survival ‐ relative dose intensity

Comparison 30: Progression‐free survival ‐ relative dose intensity, Outcome 1: Progression‐free survival ‐ relative dose intensity (amended analysis)

Figuras y tablas -
Analysis 30.1

Comparison 30: Progression‐free survival ‐ relative dose intensity, Outcome 1: Progression‐free survival ‐ relative dose intensity (amended analysis)

Comparison 30: Progression‐free survival ‐ relative dose intensity, Outcome 2: Progression‐free survival ‐ relative dose intensity

Figuras y tablas -
Analysis 30.2

Comparison 30: Progression‐free survival ‐ relative dose intensity, Outcome 2: Progression‐free survival ‐ relative dose intensity

Comparison 31: Overall response ‐ relative dose intensity, Outcome 1: Overall response ‐ relative dose intensity

Figuras y tablas -
Analysis 31.1

Comparison 31: Overall response ‐ relative dose intensity, Outcome 1: Overall response ‐ relative dose intensity

Comparison 32: Treatment‐related deaths ‐ relative dose intensity, Outcome 1: Treatment‐related deaths ‐ relative dose intensity

Figuras y tablas -
Analysis 32.1

Comparison 32: Treatment‐related deaths ‐ relative dose intensity, Outcome 1: Treatment‐related deaths ‐ relative dose intensity

Comparison 33: Neutropenia ‐ relative dose intensity, Outcome 1: Neutropaenia ‐ relative dose intensity

Figuras y tablas -
Analysis 33.1

Comparison 33: Neutropenia ‐ relative dose intensity, Outcome 1: Neutropaenia ‐ relative dose intensity

Comparison 34: Febrile neutropenia ‐ relative dose intensity, Outcome 1: Febrile neutropenia ‐ relative dose intensity

Figuras y tablas -
Analysis 34.1

Comparison 34: Febrile neutropenia ‐ relative dose intensity, Outcome 1: Febrile neutropenia ‐ relative dose intensity

Comparison 35: Nausea and vomiting ‐ relative dose intensity, Outcome 1: Nausea and vomiting ‐ relative dose intensity

Figuras y tablas -
Analysis 35.1

Comparison 35: Nausea and vomiting ‐ relative dose intensity, Outcome 1: Nausea and vomiting ‐ relative dose intensity

Table 1. Summary of treatment comparisons

Combination

Sequential

Number of trials

doxorubicin + docetaxel

doxorubicin → docetaxel

Alba 2004

Cresta 2004(included alternating regimen)

Koroleva 2001 (included 2 combination arms with different doses)

5‐fluorouracil + cyclophosphamide + vincristine

5‐fluorouracil → cyclophosphamide → vincristine

Baker 1974

capecitabine + docetaxel or paclitaxel

capecitabine → docetaxel or paclitaxel

Beslija 2006

Soto 2006

5‐fluorouracil + cyclophosphamide + prednisone + thyroxine or vincristine

5‐fluorouracil → cyclophosphamide → thyroxine or vincristine → prednisone

Chlebowski 1989

epirubicin + paclitaxel

epirubicin → paclitaxel

Conte 2004

epirubicin + paclitaxel

dose dense epirubicin→ paclitaxel

Fountzilas 2001

gemcitabine + vinorelbine

gemcitabine → vinorelbine

Park 2010

doxorubicin + paclitaxel

doxorubicin → paclitaxel or paclitaxel → doxorubicin

Sledge 2003

docetaxel + gemcitabine

docetaxel → gemcitabine

Tomova 2010

Figuras y tablas -
Table 1. Summary of treatment comparisons
Table 2. Chemotherapy details

Trial name

Arm I

Arm II

Alba 2004

Arm I: AT=

Doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 both on day 1.

Cycles repeated every 21 days for 6 cycles.

If prior anthracyclines:

given 3 cycles of AT at above doses followed by 3 cycles of docetaxel 100 mg/m2

Arm II: A→T=

Doxorubicin 75 mg/m2 intravenously day 1 for 3 cycles followed by docetaxel 100 mg/m2 intravenously day 1 for 3 cycles.

If prior anthracyclines given 2 cycles of doxorubicin 75 mg/m2 followed by 4 cycles of docetaxel 100 mg/m2.

Cycles repeated every 21 days

Baker 1974

Arm I: FCV=

5‐fluorouracil 7.5 mg/kg intravenously days 1‐5 plus cyclophosphamide 4 mg/kg intravenously days 1 to 5 plus vincristine 0.015 mg/kg intravenously days 1 and 8.

Cycles repeated every 28 days until disease progression

Arm II: F→C→V=

5‐fluorouracil 15 mg/kg intravenously days 1 to 5 every 28 days until disease progression then

cyclophosphamide 8 mg/kg intravenously days 1 to 5 every 28 days until disease progression then

vincristine 0.02 mg/kg intravenously weekly until disease progression

Beslija

2006

Arm I: XT=

Capecitabine (Xeloda, X) 1250 mg/m2 twice daily orally from days 1 to 14 and docetaxel (Taxotere, T) 75 mg/m2 intravenously day 1.

Cycle repeated every 21 days until disease progression

Arm II: T→X=

Docetaxel 100 mg/m2 intravenously day 1 until disease progression then

capecitabine 1250 mg/m2 twice daily orally from days 1 to 14 until disease progression.

Cycles repeated every 21 days

Chlebowski 1989

WCSG Arm I: CMFTP=

Cyclophosphamide 2 mg/kg/day orally, plus 5‐fluorouracil 15 mg/kg every 2 weeks intravenously from day 1, plus methotrexate 30 mg/m2 every 2 weeks intravenously beginning on day 8, plus prednisone 0.5 mg/kg/day orally, plus triiodothyronine 0.005 mg daily. Cycle repeated until disease progression.

SECSG Arm I:

Cyclophosphamide 400 mg/m2 intravenously day 1 every 28 days, plus 5‐fluorouracil 400 mg/m2 intravenously day 1 and day 8 every 28 days, plus methotrexate 30 mg/m2 intravenously day 1 and day 8 every 28 days, plus vincristine 1 mg/m2 intravenously day 1 and day 8 every 28 days, plus prednisone 80mg orally daily from days 1 to 7 every 28 days. Cycle repeated until disease progression.

or

Cyclophosphamide 100 mg orally daily, plus 5‐fluorouracil 400 mg/m2 intravenously weekly, plus methotrexate 20 mg/m2 orally weekly, plus vincristine 1 mg/m2 intravenously weekly, plus prednisone 45 mg orally daily for 14 days, then 30 mg daily for 14 days then 15 mg daily for 28 days. Cycle repeated until disease progression

WCSG Arm II: F→C→TP→M=

5‐fluorouracil 15 mg/kg weekly intravenously from day 1 for a minimum of 4 weeks until disease progression then

cyclophosphamide 2 mg/kg/day orally for a minimum of 4 weeks until disease progression then

triiodothyronine 0.005 mg daily plus prednisone 0.5 mg/kg/day for a minimum of 6 weeks until disease progression then

methotrexate 30 mg/m2 intravenously weekly for a minimum of 4 weeks

SECSG Arm II: F→MC→V→P=

5‐fluorouracil 600 mg/m2 intravenously weekly until disease progression then

methotrexate 20 mg/m2 orally biweekly until disease progression then

cyclophosphamide 100 mg/m2 orally daily until disease progression then

vincristine 1 mg/m2 intravenously weekly until disease progression then

prednisone 45 mg orally daily for 14 days then 30 mg daily for 14 days then 15 mg daily for 30 days

Conte

2004

Arm I: EP=

Epirubicin 90 mg/m2 plus paclitaxel 200 mg/m2 intravenously day 1.

Cycles repeated every 21 days for 8 cycles

Arm II: E→P=

Epirubicin 120 mg/m2 intravenously day 1 for 4 cycles then

paclitaxel 250 mg/m2 intravenously day 1 for 4 cycles.

Cycles repeated every 21 days

Cresta

2003

Arm I: AT=

Doxorubicin 60 mg/m2 plus docetaxel 60 mg/m2 intravenously day.

Cycles repeated every 21 days for 8 cycles

Arm II: A→T (sequential regimen)=

Doxorubicin 75 mg/m2 intravenously on day 1 for 4 cycles followed by docetaxel 75 mg/m2 intravenously on day 1 for 4 cycles. Cycles repeated every 21 days. Maximum 8 cycles.

Arm III: T then A (alternating regimen)=

Docetaxel 100 mg/m2 intravenously on day 1 for 4 cycles alternating with doxorubicin 75 mg/m2 intravenously on day 1 for 4 cycles. Cycles repeated every 21 days. Maximum 8 cycles

Fountzilas

2001

Arm I: P=

Epirubicin 80 mg/m2 plus paclitaxel 175 mg/m2 intravenously day 1.

Cycles repeated every 21 days for 6 cycles

Arm II: E→P

Epirubicin 110 mg/m2 intravenously day 1 for 4 cycles followed by

paclitaxel 225 mg/m2 intravenously day 1 for 4 cycles.

Cycles repeated every 14 days with G‐CSF support (dose dense regimen)

Koroleva

2001

Arm I: AT=

Doxorubicin 50 mg/m2 plus docetaxel 75 mg/m2 intravenously day 1.

Cycles repeated every 21 days for 8 cycles

Arm II: T→A=

Docetaxel 100 mg/m2 intravenously day 1 for 4 cycles followed by

doxorubicin 75 mg/m2 intravenously day 1 for 4 cycles.

Cycles repeated every 21 days.

Arm III: AT=

Doxorubicin 60 mg/m2 plus docetaxel 60 mg/m2 intravenously day 1.

Cycles repeated every 21 days for 8 cycles

Park

2010

Arm I: GV=

Gemcitabine 1,000 mg/m2 plus vinorelbine 25 mg/m2 intravenously days 1 and 8.

Cycles repeated every 21 days until disease progression

Arm II: G→V=

Gemcitabine 1,200 mg/m2 intravenously on days 1 and 8 until disease progression then

vinorelbine 30 mg/m2 intravenously days 1 and 8 until disease progression.

Cycles repeated every 21 days

Sledge

2003

Arm I: AT=

Doxorubicin 50 mg/m2 plus paclitaxel 150 mg/m2 over 24 hours intravenously day 1.

Cycles repeated every 21 days until disease progression

Arm II: A (→P)=

Doxorubicin 60 mg/m2 intravenously day 1 for a maximum of 8 cycles. If disease progressed crossed over to paclitaxel 175 mg/m2 intravenously over 24 hours on day 1.

Cycles repeated every 21 days.

Arm III: P (→A)=

Paclitaxel 175 mg/m2 intravenously over 24 hours on day 1. If disease progressed crossed over to doxorubicin 60 mg/m2 intravenously day 1.

Cycles repeated every 21 days

Soto

2006

Arm I: XT=

Capecitabine 825 mg/m2 twice daily orally from days 1 to 14 plus docetaxel 75 mg/m2 intravenously on day 1 until disease progression.

Cycles repeated every 21 days

Arm II: X→T (docetaxel or paclitaxel)=

Capecitabine 1250 mg/m2 twice daily orally days 1 to 14 until disease progression then

docetaxel 100 mg/m2 or paclitaxel 175 mg/m2 intravenously on day 1 until disease progression.

Cycles repeated every 21 days.

Arm III: XP=

Capecitabine 825 mg/m2 twice daily orally from days 1 to 14 plus paclitaxel 175 mg/m2 intravenously on day 1 until disease progression.

Cycles repeated every 21 days

Tomova

2010

Arm I: TG=

Docetaxel 75 mg/m2 intravenously on day 1 plus gemcitabine 1,000 mg/m2 intravenously on days 1 and 8.

Cycles repeated every 21 days for 8 cycles

Arm II: T→G=

Docetaxel 100 mg/m2 intravenously on day 1 for 4 cycles followed by

gemcitabine 1,250 mg/m2 intravenously on days 1 and 1 for 4 cycles.

Cycles repeated every 21 days

Figuras y tablas -
Table 2. Chemotherapy details
Comparison 1. Overall survival

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Overall survival (all trials) Show forest plot

9

1786

Hazard Ratio (IV, Fixed, 95% CI)

1.04 [0.93, 1.16]

Figuras y tablas -
Comparison 1. Overall survival
Comparison 2. Progression‐free survival

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Progression‐free survival (amended analysis) Show forest plot

7

1483

Hazard Ratio (IV, Fixed, 95% CI)

1.11 [0.99, 1.25]

2.2 Progression‐free survival (all trials) Show forest plot

8

Hazard Ratio (IV, Fixed, 95% CI)

1.16 [1.03, 1.31]

Figuras y tablas -
Comparison 2. Progression‐free survival
Comparison 3. Overall response

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Overall response (all trials) Show forest plot

12

2140

Risk Ratio (IV, Fixed, 95% CI)

1.16 [1.06, 1.28]

Figuras y tablas -
Comparison 3. Overall response
Comparison 4. Treatment‐related deaths

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 Treatment‐related deaths (all trials) Show forest plot

7

902

Risk Ratio (M‐H, Fixed, 95% CI)

1.53 [0.71, 3.29]

Figuras y tablas -
Comparison 4. Treatment‐related deaths
Comparison 5. Neutropenia

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

5.1 Neutropaenia Show forest plot

12

Risk Ratio (IV, Fixed, 95% CI)

0.94 [0.87, 1.02]

Figuras y tablas -
Comparison 5. Neutropenia
Comparison 6. Febrile neutropenia

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

6.1 Febrile neutropenia Show forest plot

9

Risk Ratio (IV, Fixed, 95% CI)

1.32 [1.06, 1.65]

Figuras y tablas -
Comparison 6. Febrile neutropenia
Comparison 7. Nausea and vomiting

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

7.1 Nausea and vomiting Show forest plot

8

Risk Ratio (IV, Fixed, 95% CI)

0.88 [0.57, 1.34]

Figuras y tablas -
Comparison 7. Nausea and vomiting
Comparison 8. Overall survival ‐ risk of bias

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

8.1 Overall survival ‐ risk of bias Show forest plot

9

Hazard Ratio (IV, Fixed, 95% CI)

1.04 [0.93, 1.16]

8.1.1 Low risk of bias

2

Hazard Ratio (IV, Fixed, 95% CI)

1.21 [0.93, 1.58]

8.1.2 High/unclear risk of bias

7

Hazard Ratio (IV, Fixed, 95% CI)

1.01 [0.90, 1.14]

Figuras y tablas -
Comparison 8. Overall survival ‐ risk of bias
Comparison 9. Progression‐free survival ‐ risk of bias

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

9.1 Progression‐free survival ‐ risk of bias (amended analysis) Show forest plot

7

Hazard Ratio (IV, Fixed, 95% CI)

1.11 [0.99, 1.25]

9.1.1 Low risk of bias

2

Hazard Ratio (IV, Fixed, 95% CI)

1.15 [0.94, 1.41]

9.1.2 High/unclear risk of bias

5

Hazard Ratio (IV, Fixed, 95% CI)

1.09 [0.94, 1.26]

9.2 Progression‐free survival ‐ risk of bias Show forest plot

8

Hazard Ratio (IV, Fixed, 95% CI)

1.16 [1.03, 1.31]

9.2.1 Low risk of bias

2

Hazard Ratio (IV, Fixed, 95% CI)

1.15 [0.94, 1.41]

9.2.2 High/unclear risk of bias

6

Hazard Ratio (IV, Fixed, 95% CI)

1.17 [1.01, 1.35]

Figuras y tablas -
Comparison 9. Progression‐free survival ‐ risk of bias
Comparison 10. Overall response ‐ risk of bias

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

10.1 Overall response ‐ risk of bias Show forest plot

12

2140

Risk Ratio (IV, Fixed, 95% CI)

1.16 [1.06, 1.28]

10.1.1 Low risk of bias

2

381

Risk Ratio (IV, Fixed, 95% CI)

0.91 [0.76, 1.10]

10.1.2 High/unclear risk of bias

10

1759

Risk Ratio (IV, Fixed, 95% CI)

1.26 [1.13, 1.39]

Figuras y tablas -
Comparison 10. Overall response ‐ risk of bias
Comparison 11. Treatment‐related deaths ‐ risk of bias

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

11.1 Treatment‐related deaths ‐ risk of bias Show forest plot

7

902

Risk Ratio (M‐H, Fixed, 95% CI)

1.53 [0.71, 3.29]

11.1.1 Low risk of bias

1

198

Risk Ratio (M‐H, Fixed, 95% CI)

2.60 [0.28, 24.60]

11.1.2 High/unclear risk of bias

6

704

Risk Ratio (M‐H, Fixed, 95% CI)

1.41 [0.62, 3.20]

Figuras y tablas -
Comparison 11. Treatment‐related deaths ‐ risk of bias
Comparison 12. Neutropenia ‐ risk of bias

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

12.1 Neutropaenia ‐ risk of bias Show forest plot

12

Risk Ratio (IV, Fixed, 95% CI)

0.94 [0.87, 1.02]

12.1.1 Low risk of bias

2

Risk Ratio (IV, Fixed, 95% CI)

0.62 [0.50, 0.76]

12.1.2 High/unclear risk of bias

10

Risk Ratio (IV, Fixed, 95% CI)

1.00 [0.92, 1.09]

Figuras y tablas -
Comparison 12. Neutropenia ‐ risk of bias
Comparison 13. Febrile neutropenia ‐ risk of bias

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

13.1 Febrile neutropenia ‐ risk of bias Show forest plot

9

Risk Ratio (IV, Fixed, 95% CI)

1.32 [1.06, 1.65]

13.1.1 Low risk of bias

2

Risk Ratio (IV, Fixed, 95% CI)

1.60 [0.72, 3.57]

13.1.2 High/unclear risk of bias

7

Risk Ratio (IV, Fixed, 95% CI)

1.30 [1.03, 1.64]

Figuras y tablas -
Comparison 13. Febrile neutropenia ‐ risk of bias
Comparison 14. Nausea and vomiting ‐ risk of bias

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

14.1 Nausea and vomiting ‐ risk of bias Show forest plot

8

Risk Ratio (IV, Fixed, 95% CI)

0.88 [0.57, 1.34]

14.1.1 Low risk of bias

1

Risk Ratio (IV, Fixed, 95% CI)

1.03 [0.21, 4.99]

14.1.2 High/unclear risk of bias

7

Risk Ratio (IV, Fixed, 95% CI)

0.87 [0.56, 1.35]

Figuras y tablas -
Comparison 14. Nausea and vomiting ‐ risk of bias
Comparison 15. Overall survival ‐ line of chemotherapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

15.1 Overall survival ‐ line of chemotherapy Show forest plot

9

Hazard Ratio (IV, Fixed, 95% CI)

1.04 [0.93, 1.16]

15.1.1 First line chemotherapy

7

Hazard Ratio (IV, Fixed, 95% CI)

1.04 [0.93, 1.18]

15.1.2 Second/third line chemotherapy

2

Hazard Ratio (IV, Fixed, 95% CI)

1.03 [0.76, 1.40]

Figuras y tablas -
Comparison 15. Overall survival ‐ line of chemotherapy
Comparison 16. Progression‐free survival ‐ line of chemotherapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

16.1 Progression free survival ‐ line of chemotherapy (amended analysis) Show forest plot

7

Hazard Ratio (IV, Fixed, 95% CI)

1.11 [0.99, 1.25]

16.1.1 First line chemotherapy

6

Hazard Ratio (IV, Fixed, 95% CI)

1.11 [0.99, 1.26]

16.1.2 Second/third line chemotherapy

1

Hazard Ratio (IV, Fixed, 95% CI)

0.85 [0.24, 2.99]

16.2 Progression free survival ‐ line of chemotherapy Show forest plot

8

Hazard Ratio (IV, Fixed, 95% CI)

1.16 [1.03, 1.31]

16.2.1 First line chemotherapy

6

Hazard Ratio (IV, Fixed, 95% CI)

1.16 [1.02, 1.31]

16.2.2 Second/third line chemotherapy

2

Hazard Ratio (IV, Fixed, 95% CI)

1.25 [0.80, 1.95]

Figuras y tablas -
Comparison 16. Progression‐free survival ‐ line of chemotherapy
Comparison 17. Overall response ‐ line of chemotherapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

17.1 Overall response ‐ subgroup analysis, line of chemotherapy Show forest plot

12

2140

Risk Ratio (IV, Fixed, 95% CI)

1.16 [1.06, 1.28]

17.1.1 First line chemotherapy

9

1778

Risk Ratio (IV, Fixed, 95% CI)

1.10 [1.00, 1.22]

17.1.2 Second/third line chemotherapy

3

362

Risk Ratio (IV, Fixed, 95% CI)

1.54 [1.22, 1.93]

Figuras y tablas -
Comparison 17. Overall response ‐ line of chemotherapy
Comparison 18. Treatment‐related deaths ‐ line of chemotherapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

18.1 Treatment‐related deaths ‐ line of chemotherapy Show forest plot

7

902

Risk Ratio (M‐H, Fixed, 95% CI)

1.53 [0.71, 3.29]

18.1.1 First line chemotherapy

5

722

Risk Ratio (M‐H, Fixed, 95% CI)

1.72 [0.70, 4.18]

18.1.2 Second/third line chemotherapy

2

180

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.23, 4.94]

Figuras y tablas -
Comparison 18. Treatment‐related deaths ‐ line of chemotherapy
Comparison 19. Neutropenia ‐ line of chemotherapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

19.1 Neutropaenia ‐ line of chemotherapy Show forest plot

12

Risk Ratio (IV, Fixed, 95% CI)

0.92 [0.84, 1.01]

19.1.1 First‐line chemotherapy

9

Risk Ratio (IV, Fixed, 95% CI)

0.96 [0.87, 1.05]

19.1.2 Second/third‐line chemotherapy

3

Risk Ratio (IV, Fixed, 95% CI)

0.64 [0.48, 0.85]

Figuras y tablas -
Comparison 19. Neutropenia ‐ line of chemotherapy
Comparison 20. Febrile neutropenia ‐ line of chemotherapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

20.1 Febrile neutropenia ‐ line of chemotherapy Show forest plot

9

Risk Ratio (IV, Fixed, 95% CI)

1.32 [1.06, 1.65]

20.1.1 First‐line chemotherapy

7

Risk Ratio (IV, Fixed, 95% CI)

1.34 [1.07, 1.68]

20.1.2 Second/third‐line chemotherapy

2

Risk Ratio (IV, Fixed, 95% CI)

0.86 [0.24, 3.15]

Figuras y tablas -
Comparison 20. Febrile neutropenia ‐ line of chemotherapy
Comparison 21. Nausea and vomiting ‐ line of chemotherapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

21.1 Nausea and vomiting ‐ line of chemotherapy Show forest plot

8

Risk Ratio (IV, Fixed, 95% CI)

0.88 [0.57, 1.34]

21.1.1 First‐line chemotherapy

5

Risk Ratio (IV, Fixed, 95% CI)

0.85 [0.55, 1.33]

21.1.2 Second/third‐line chemotherapy

3

Risk Ratio (IV, Fixed, 95% CI)

1.25 [0.27, 5.74]

Figuras y tablas -
Comparison 21. Nausea and vomiting ‐ line of chemotherapy
Comparison 22. Overall survival ‐ schema 1 versus schema 2

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

22.1 Overall survival ‐ Schema 1 versus Schema 2 Show forest plot

9

Hazard Ratio (IV, Fixed, 95% CI)

1.04 [0.93, 1.16]

22.1.1 Schema 1

5

Hazard Ratio (IV, Fixed, 95% CI)

0.98 [0.86, 1.12]

22.1.2 Schema 2

4

Hazard Ratio (IV, Fixed, 95% CI)

1.22 [0.99, 1.49]

Figuras y tablas -
Comparison 22. Overall survival ‐ schema 1 versus schema 2
Comparison 23. Progression‐free survival ‐ schema 1 versus schema 2

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

23.1 Progression‐free survival ‐ Schema 1 versus Schema 2 (amended analysis) Show forest plot

7

Hazard Ratio (IV, Fixed, 95% CI)

1.11 [0.99, 1.25]

23.1.1 Schema 1

3

Hazard Ratio (IV, Fixed, 95% CI)

1.11 [0.94, 1.31]

23.1.2 Schema 2

4

Hazard Ratio (IV, Fixed, 95% CI)

1.12 [0.94, 1.33]

23.2 Progression‐free survival ‐ Schema 1 versus Schema 2 Show forest plot

8

Hazard Ratio (IV, Fixed, 95% CI)

1.16 [1.03, 1.31]

23.2.1 Schema 1

4

Hazard Ratio (IV, Fixed, 95% CI)

1.20 [1.03, 1.40]

23.2.2 Schema 2

4

Hazard Ratio (IV, Fixed, 95% CI)

1.12 [0.94, 1.33]

Figuras y tablas -
Comparison 23. Progression‐free survival ‐ schema 1 versus schema 2
Comparison 24. Overall response ‐ schema 1 versus schema 2

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

24.1 Overall response ‐ Schema 1 versus Schema 2 Show forest plot

12

2140

Risk Ratio (IV, Fixed, 95% CI)

1.16 [1.06, 1.28]

24.1.1 Schema 1

6

1344

Risk Ratio (IV, Fixed, 95% CI)

1.46 [1.28, 1.65]

24.1.2 Schema 2

6

796

Risk Ratio (IV, Fixed, 95% CI)

0.92 [0.80, 1.04]

Figuras y tablas -
Comparison 24. Overall response ‐ schema 1 versus schema 2
Comparison 25. Treatment‐related deaths ‐ schema 1 versus schema 2

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

25.1 Treatment‐related deaths ‐ Schema 1 versus Schema 2 Show forest plot

7

902

Risk Ratio (M‐H, Fixed, 95% CI)

1.53 [0.71, 3.29]

25.1.1 Schema 1

3

379

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.36, 2.44]

25.1.2 Schema 2

4

523

Risk Ratio (M‐H, Fixed, 95% CI)

4.00 [0.87, 18.35]

Figuras y tablas -
Comparison 25. Treatment‐related deaths ‐ schema 1 versus schema 2
Comparison 26. Neutropenia ‐ schema 1 versus schema 2

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

26.1 Neutropaenia ‐ subgroup analysis, Schema 1 versus Schema 2 Show forest plot

12

Risk Ratio (IV, Fixed, 95% CI)

0.94 [0.87, 1.02]

26.1.1 Schema 1

6

Risk Ratio (IV, Fixed, 95% CI)

0.99 [0.87, 1.14]

26.1.2 Schema 2

6

Risk Ratio (IV, Fixed, 95% CI)

0.92 [0.84, 1.01]

Figuras y tablas -
Comparison 26. Neutropenia ‐ schema 1 versus schema 2
Comparison 27. Febrile neutropenia ‐ schema 1 versus schema 2

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

27.1 Febrile neutropenia ‐ Schema 1 versus Schema 2 Show forest plot

9

Risk Ratio (IV, Fixed, 95% CI)

1.32 [1.06, 1.65]

27.1.1 Schema 1

3

Risk Ratio (IV, Fixed, 95% CI)

1.76 [1.14, 2.73]

27.1.2 Schema 2

6

Risk Ratio (IV, Fixed, 95% CI)

1.19 [0.92, 1.55]

Figuras y tablas -
Comparison 27. Febrile neutropenia ‐ schema 1 versus schema 2
Comparison 28. Nausea and vomiting ‐ schema 1 versus schema 2

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

28.1 Nausea and vomiting ‐ Schema 1 versus Schema 2 Show forest plot

8

Risk Ratio (IV, Fixed, 95% CI)

0.88 [0.57, 1.34]

28.1.1 Schema 1

3

Risk Ratio (IV, Fixed, 95% CI)

0.75 [0.39, 1.46]

28.1.2 Schema 2

5

Risk Ratio (IV, Fixed, 95% CI)

0.98 [0.56, 1.71]

Figuras y tablas -
Comparison 28. Nausea and vomiting ‐ schema 1 versus schema 2
Comparison 29. Overall survival ‐ relative dose intensity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

29.1 Overall survival ‐ relative dose intensity Show forest plot

4

Hazard Ratio (IV, Fixed, 95% CI)

1.14 [0.92, 1.39]

29.1.1 Similar dose intensity

2

Hazard Ratio (IV, Fixed, 95% CI)

1.23 [0.93, 1.62]

29.1.2 Different dose intensity

2

Hazard Ratio (IV, Fixed, 95% CI)

1.03 [0.76, 1.40]

Figuras y tablas -
Comparison 29. Overall survival ‐ relative dose intensity
Comparison 30. Progression‐free survival ‐ relative dose intensity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

30.1 Progression‐free survival ‐ relative dose intensity (amended analysis) Show forest plot

3

Hazard Ratio (IV, Fixed, 95% CI)

1.13 [0.90, 1.43]

30.1.1 Similar dose intensity

2

Hazard Ratio (IV, Fixed, 95% CI)

1.15 [0.91, 1.45]

30.1.2 Different dose intensity

1

Hazard Ratio (IV, Fixed, 95% CI)

0.85 [0.24, 2.99]

30.2 Progression‐free survival ‐ relative dose intensity Show forest plot

4

Hazard Ratio (IV, Fixed, 95% CI)

1.17 [0.95, 1.44]

30.2.1 Similar dose intensity

2

Hazard Ratio (IV, Fixed, 95% CI)

1.15 [0.91, 1.45]

30.2.2 Different dose intensity

2

Hazard Ratio (IV, Fixed, 95% CI)

1.25 [0.80, 1.95]

Figuras y tablas -
Comparison 30. Progression‐free survival ‐ relative dose intensity
Comparison 31. Overall response ‐ relative dose intensity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

31.1 Overall response ‐ relative dose intensity Show forest plot

6

679

Risk Ratio (IV, Fixed, 95% CI)

0.90 [0.77, 1.05]

31.1.1 Similar dose intensity

3

355

Risk Ratio (IV, Fixed, 95% CI)

0.88 [0.72, 1.07]

31.1.2 Different dose intensity

3

324

Risk Ratio (IV, Fixed, 95% CI)

0.93 [0.72, 1.20]

Figuras y tablas -
Comparison 31. Overall response ‐ relative dose intensity
Comparison 32. Treatment‐related deaths ‐ relative dose intensity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

32.1 Treatment‐related deaths ‐ relative dose intensity Show forest plot

4

406

Risk Ratio (M‐H, Fixed, 95% CI)

1.66 [0.45, 6.10]

32.1.1 Similar dose intensity

1

82

Risk Ratio (M‐H, Fixed, 95% CI)

Not estimable

32.1.2 Different dose intensity

3

324

Risk Ratio (M‐H, Fixed, 95% CI)

1.66 [0.45, 6.10]

Figuras y tablas -
Comparison 32. Treatment‐related deaths ‐ relative dose intensity
Comparison 33. Neutropenia ‐ relative dose intensity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

33.1 Neutropaenia ‐ relative dose intensity Show forest plot

6

Risk Ratio (IV, Fixed, 95% CI)

1.01 [0.92, 1.12]

33.1.1 Similar dose intensity

3

Risk Ratio (IV, Fixed, 95% CI)

1.08 [0.97, 1.20]

33.1.2 Different dose intensity

3

Risk Ratio (IV, Fixed, 95% CI)

0.67 [0.51, 0.87]

Figuras y tablas -
Comparison 33. Neutropenia ‐ relative dose intensity
Comparison 34. Febrile neutropenia ‐ relative dose intensity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

34.1 Febrile neutropenia ‐ relative dose intensity Show forest plot

6

Risk Ratio (IV, Fixed, 95% CI)

1.21 [0.93, 1.57]

34.1.1 Similar dose intensity

3

Risk Ratio (IV, Fixed, 95% CI)

2.36 [1.21, 4.62]

34.1.2 Different dose intensity

3

Risk Ratio (IV, Fixed, 95% CI)

1.07 [0.80, 1.42]

Figuras y tablas -
Comparison 34. Febrile neutropenia ‐ relative dose intensity
Comparison 35. Nausea and vomiting ‐ relative dose intensity

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

35.1 Nausea and vomiting ‐ relative dose intensity Show forest plot

6

Risk Ratio (IV, Fixed, 95% CI)

0.98 [0.56, 1.71]

35.1.1 Similar dose intensity

3

Risk Ratio (IV, Fixed, 95% CI)

1.14 [0.50, 2.60]

35.1.2 Different dose intensity

3

Risk Ratio (IV, Fixed, 95% CI)

0.86 [0.40, 1.83]

Figuras y tablas -
Comparison 35. Nausea and vomiting ‐ relative dose intensity