نقش گرلین در مدیریت کاشکسی مرتبط با سرطان
Información
- DOI:
- https://doi.org/10.1002/14651858.CD012229.pub2Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 28 febrero 2018see what's new
- Tipo:
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- Intervention
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Dolor y cuidados paliativos
- Copyright:
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- Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cifras del artículo
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Autores
Contributions of authors
MNK: led the design of the review as primary author, implemented search strategy with the help of Cochrane Pain, Palliative and Supportive Care's Information Specialist, screened the articles on the basis of title and abstract, extracted and analysed data, and led the write‐up.
AS: closely helped in design, resolved discrepancy in screening, aided in analysis and write‐up
RK: closely helped in design, provided statistical inputs for analysis, and assisted with the write‐up
AG: closely helped in design, screened full texts, provided statistical inputs for analysis, and assisted with the write‐up
SG: closely helped in design, screened the articles on the basis of title and abstract, extracted data, and assisted with the write‐up
PS: closely helped in design, assessed the risk of bias for each study, and assisted with the write‐up
ZQS: closely helped in design, screened full texts, provided statistical inputs for analysis, and assisted the write‐up
All authors are responsible for the full review, and updating the review in future.
Sources of support
Internal sources
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Datta Meghe Institute of Medical Sciences, India
External sources
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No sources of support supplied
Declarations of interest
MNK: none known
AS: none known
RK: none known
AG: none known
SG: none known. SG is a specialist physician and manages patients with cancer cachexia.
PS: none known
ZQS: none known
Acknowledgements
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We acknowledge the support of Dr Prathap Tharyan, Director, South Asian Cochrane Network & Center, Prof. BV Moses Center for Evidence‐Informed Health Care and Health Policy, Christian Medical College, Vellore, India.
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Cochrane Review Group funding acknowledgement: this project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to Cochrane Pain, Palliative and Supportive Care (PaPaS). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service, or the Department of Health
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We acknowledge the external peer referees Dr Ollie Minton, consultant and senior lecturer in palliative medicine, Roger Goucke, anaesthesia/palliative Care, Maria J Silveira, palliative care specialist and researcher, and Marília Seelaender, head of the Cancer Metabolism Group, University of São Paulo, for providing valuable input to the protocol. We also thank Joanne Abbott for developing the search strategy.
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We acknowledge the external peer referees Marilia Seelaender, Dr Adrian Tookman, Bridget Candy and consumer referee Corrie Billedeau for providing valuable input to this review.
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We acknowledge the support of Dr Vedprakash Mishra, Dr Tripti Shrivastava, Dr Mahjabeen Ahmed, Dr Deepak Saxena, Dr B Unnikrishnan and Mahafroz Khatib during the preparation of the review.
Version history
| Published | Title | Stage | Authors | Version |
| 2018 Feb 28 | Ghrelin for the management of cachexia associated with cancer | Review | Mahalaqua Nazli Khatib, Anuraj H Shankar, Richard Kirubakaran, Abhay Gaidhane, Shilpa Gaidhane, Padam Simkhada, Zahiruddin Quazi Syed | |
| 2016 Jun 03 | Ghrelin for the management of cachexia associated with cancer | Protocol | Mahalaqua Nazli Khatib, Anuraj Shankar, Richard Kirubakaran, Abhay Gaidhane, Shilpa Gaidhane, Padam Simkhada, Zahiruddin Quazi Syed | |
Differences between protocol and review
We updated the background section with recent references.
We had planned to undertake five comparisons. We added a sixth comparison group in this review: higher‐dose ghrelin versus lower‐dose ghrelin as we found two studies addressing this. We thought it wiser to include this comparison rather than miss data on an intervention.
We had intended to use changed scores for all our outcomes. However, for food intake, body composition, plasma ghrelin levels and quality of life (under comparison of ghrelin versus placebo), we presented the baseline and the end‐scores, as the data for changed scores were not available and could not be computed (Table 1; Table 2).
In the protocol, we had planned to include 'Summary of findings' tables for three comparisons: ghrelin versus placebo, ghrelin versus an alternative experimental treatment modality, and ghrelin in combination with other treatments versus ghrelin treatment alone. However, as per the availability of the data, we have included 'Summary of findings' tables for another comparison group: higher‐dose ghrelin versus lower‐dose ghrelin in this review.
Notes
Assessed for updating in 2020
In July 2020 we did not identify any potentially relevant studies likely to change the conclusions. Therefore, this review has now been stabilised following discussion with the authors and editors. The review will be re‐assessed for updating in two years. If appropriate, we will update the review before this date if new evidence likely to change the conclusions is published, or if standards change substantially which necessitate major revisions.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
Medical Subject Headings Check Words
Aged; Female; Humans; Male; Middle Aged;
PICO
Study flow diagram
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
| Ghrelin compared to placebo for cachexia associated with cancer | ||||||
| Patient or population: people with cachexia associated with cancer Settings: hospital | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo | Risk with ghrelin | |||||
| Food intake | Not known | Not known | Not known | 7 | ⊕⊝⊝⊝ | The study reported, "31% increase in energy intake with ghrelin infusion" Too few data to be meaningful |
| Body weight | No data | No data | No data | No data | ⊕⊝⊝⊝ | Not reported. No data available. No evidence to support or refute the use of ghrelin in people with cancer cachexia |
| Adverse events | Study population | Not estimable | 7 | ⊕⊝⊝⊝ | The study reported, "No side effects were observed" Too few data and number of events too small to be meaningful | |
| 0 per 1000 | 0 per 1000 | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded once for study limitations due to high risk of attrition bias and biases confounded by small size. | ||||||
| Ghrelin compared to alternative experimental treatment modality for cachexia associated with cancer | ||||||
| Patient or population: people with cancer cachexia Settings: hospital | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with alternative experimental treatment modality | Risk with ghrelin | |||||
| Food intake | No data | No data | No data | No data | ⊕⊝⊝⊝ | Not reported. No evidence to support or refute the use of ghrelin in people with cancer cachexia. |
| Body weight | No data | No data | No data | No data | ⊕⊝⊝⊝ | Not reported. No evidence to support or refute the use of ghrelin in people with cancer cachexia. |
| Adverse events | No data | No data | No data | No data | ⊕⊝⊝⊝ | Not reported. No evidence to support or refute the use of ghrelin in people with cancer cachexia. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1In circumstances where there were no data reported for an outcome, we report the level of evidence as 'very low' with no evidence to support or refute the use of ghrelin in people with cancer cachexia. | ||||||
| Ghrelin in combination with other treatments compared to ghrelin treatment alone for cachexia associated with cancer | ||||||
| Patient or population: people with cancer cachexia Settings: hospital | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with ghrelin treatment alone | Risk with ghrelin in combination with other treatments | |||||
| Food intake | No data | No data | No data | No data | ⊕⊝⊝⊝ | Not reported. No evidence to support or refute the use of ghrelin in people with cancer cachexia. |
| Body weight | No data | No data | No data | No data | ⊕⊝⊝⊝ | Not reported. No evidence to support or refute the use of ghrelin in people with cancer cachexia. |
| Adverse events | No data | No data | No data | No data | ⊕⊝⊝⊝ | Not reported. No evidence to support or refute the use of ghrelin in people with cancer cachexia. |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1In circumstances where there were no data reported for an outcome, we report the level of evidence as 'very low' with no evidence to support or refute the use of ghrelin in people with cancer cachexia. | ||||||
| Higher‐dose ghrelin compared to lower‐dose ghrelin for cachexia associated with cancer | ||||||
| Patient or population: people with cancer cachexia Settings: hospital | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Quality of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with lower‐dose ghrelin | Risk with higher‐dose ghrelin | |||||
| Food intake | See comment | See comment | N/A | 40 | ⊕⊝⊝⊝ | Too few data to be meaningful Because of the differences in study design and diversity in the treatment provided we did not pool results in a meta‐analysis |
| Body weight | No data | No data | No data | No data | ⊕⊝⊝⊝ | Not reported. No evidence to support or refute the use of ghrelin in people with cancer cachexia. |
| Adverse events | Study population | Not estimable | 40 | ⊕⊝⊝⊝ | Too few data to be meaningful | |
| See comment | See comment | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded once for study limitations due to high risk of attrition bias and biases confounded by small size. | ||||||
| Primary outcome | ||||||
|---|---|---|---|---|---|---|
| Higher‐dose ghrelin group | Lower‐dose ghrelin group | Ghrelin group | Placebo group | Higher‐dose ghrelin group | Lower‐dose ghrelin group | |
| Food intake | Baseline: 32.5 ± 94 (SEM) kcal/kg/day At 8 weeks: 28.2 ± 3.8 (SEM) kcal/kg/day According to 4‐day schedule | Baseline: 24.1 ± 3.0 (SEM) kcal/kg/day At 8 weeks: 25.5 ± 4.5 (SEM) kcal/kg/day According to 4‐day schedule | Mean energy intake: 9270 kJ (95% CI 3249 to 15,290 kJ) As assessed by 24‐h food diary | Mean energy intake: 6854 kJ (95% CI 3634 to 10,070 kJ) As assessed by 24‐h food diary | Nutritrional intake at lunch compared to baseline Ghrelin: 251 kcal Placebo: 230 kcal Nutritrional intake at lunch and rest of the day compared to baseline Ghrelin: 244 kcal Placebo: 156 kcal Monitored daily | Nutritrional intake at lunch compared to baseline Ghrelin: ‐105 kcal Placebo: ‐17 kcal Nutritrional intake at lunch and rest of the day compared to baseline Ghrelin: 145 kcal Placebo: 228 kcal Monitored daily |
| Body weight | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported |
| Adverse events | Nil | Nil | Nil | Nil | Ghrelin: 17 (increased bowel activity: 5; abdominal pain: 5; dry mouth: 3; worsening of pre‐existing neuropathy: 1; asthenia: 1; diarrhoea: 1; nausea: 1) Placebo: 6 (increased bowel activity: 3; dry mouth: 1; dizziness: 1; diarrhoea: 1) | Ghrelin: 7 (increased bowel activity: 3; shortness of breath: 1; sweating: 2; vomiting: 1) Placebo: 12 (increased bowel activity: 5; shortness of breath: 1; nausea: 1; increased stool frequency: 1; apoplectiform deafness: 1; vomiting: 2; constipation: 1) |
| SEM: standard error of mean | ||||||
| Secondary Outcomes | ||||||
|---|---|---|---|---|---|---|
| Higher‐dose ghrelin group | Lower‐dose ghrelin group | Ghrelin group | Placebo group | Higher‐dose ghrelin group | Lower‐dose ghrelin group | |
| Survival | Not reported | Not reported | Not reported | Not reported | Not reported | Not reported |
| Body composition (lean body mass) | Baseline: 44.8 ± 2.9 (SEM) kg At 8 weeks: 47.8 ± 2.9 (SEM) kg Difference over time: 2.24 ± 0.71 (SEM) | Baseline: 44.3 ± 2.2 (SEM) kg At 8 weeks: 45.1 ± 2.8 (SEM) kg Difference over time: 0.86 ± 1.18 (SEM) | Not reported | Not reported | Not reported | Not reported |
| Mean difference 1.38 kg (95% CI ‐1.32 to 4.08) | ||||||
| Body composition (fat mass) | Baseline: 15.1 ± 1.9 (SEM) kg At 8 weeks: 13.5 ± 1.9 (SEM) kg Difference over time: ‐1.3 ± 0.7 (SEM) | Baseline: 16.3 ± 3.0 (SEM) kg At 8 weeks: 12.6 ± 2.4 (SEM) kg Difference over time: ‐3.7 ± 0.8 (SEM) | Not reported | Not reported | Not reported | Not reported |
| Mean difference 2.40 kg (95% CI 0.32 to 4.48 | ||||||
| Plasma ghrelin | Baseline: 563 ± 90 (SEM) ng/L At 8 weeks: 1229 ± 501 (SEM) ng/L | Baseline: 3418 ± 2570 (SEM) ng/L At 8 weeks: 3817 ± 2997 (SEM) ng/L | 0 min (pre‐breakfast): 531 ± 83 (SEM) 90 min (at the start of infusion): 505 ± 90 (SEM) 150 min (60 min after the start of infusion): 1718 ± 169 (SEM) 180 min (90 min after the start of infusion): 1840 ± 221 (SEM) | 0 min (pre‐breakfast): 545 ± 58 (SEM) 90 min (at the start of infusion): 440 ± 59 (SEM) 150 min (60 min after the start of infusion): 509 ± 97 (SEM) 180 min (90 min after the start of infusion): 490 ± 63 (SEM) | Not reported | Not reported |
| Baseline imbalances between the two groups | Mean difference 1209.00 pmoL/L (95% CI 827.08 to 1590.92) | |||||
| Quality of Life | HADS anxiety Baseline: 4.6 ± 1.07 (SEM) At 8 weeks: 5.4 ± 1.6 (SEM) | HADS anxiety Baseline: 8.6 ± 1.6 (SEM) At 8 weeks: 8.8 ± 1.3 (SEM) | Not reported | Not reported | Not reported | Not reported |
| Baseline imbalances between the two groups | ||||||
| HADS depression Baseline: 5.7 ± 0.9 (SEM) At 8 weeks: 6.8 ±1.2 (SEM) | HADS depression Baseline: 7.6 ±1.4 (SEM) At 8 weeks: 9.3 ± 1.9 (SEM) | Not reported | Not reported | Not reported | Not reported | |
| Mean difference ‐2.50 (95% CI ‐6.90 to 1.90) | ||||||
| SF‐36 PCS Baseline: 30 ± 3 (SEM) At 8 weeks: 27 ± 3 (SEM) | SF‐36 PCS Baseline: 35 ± 3 (SEM) At 8 weeks: 30 ± 2 (SEM) | Not reported | Not reported | Not reported | Not reported | |
| Mean difference ‐3.00 (95% CI ‐10.07 to 4.07) | ||||||
| SF‐36 MCS Baseline: 40 ± 3 (SEM) At 8 weeks: 41 ± 3 (SEM) | SF‐36 MCS Baseline: 30 ± 2 (SEM) At 8 weeks: 34 ± 4 (SEM) | Not reported | Not reported | Not reported | Not reported | |
| Baseline imbalances | ||||||
| CI: confidence interval | ||||||
