Sanaati et al. (2016): Effect of Ginger and Chamomile on Nausea and Vomiting Caused by Chemotherapy in Iranian Women with Breast Cancer

Reference ↗
Title	Effect of Ginger and Chamomile on Nausea and Vomiting Caused by Chemotherapy in Iranian Women with Breast Cancer
Topic	Ginger
Author	Sanaati, F, Najafi, S, Kashaninia, Z, Sadeghi, M
Year	2016
Journal	Asian Pacific Journal of Cancer Prevention
DOI	https://doi.org/10.14456/apjcp.2016.225/APJCP.2016.17.8.4125

Brief summary

65 breast cancer patients were randomly divided into three groups, one arm received 1000mg ginger (standardized in capsules), the other arm received the same amount of chamomile extract in capsules, the third arm received only standard therapy. All arms also received standard medication to reduce nausea/vomiting, as well as aprepitant. The treatment was started 5 days before the start of chemotherapy and stopped 5 days after the end. The chemotherapy regimen is not reported. The ginger arm had significantly fewer episodes of nausea and the frequency of vomiting was significantly lower than in the arm that received neither ginger nor chamomile. The study is not well reported, suggesting that the study was not methodologically well conducted and the results must be interpreted with caution.

65 Brustkrebspatientinnen wurden zufällig in drei Gruppen aufgeteilt, die eine Gruppe erhielt 1000mg Ingwer (standardisiert hergestellt in Kapseln), die andere Gruppe erhielt die gleiche Menge Kamilleextrakt in Kapseln, die dritte Gruppe erhielt nur Standardtherapie. Alle Gruppen erhielten zusätzlich Standardmedikamente zur Eindämmung von Übelkeit/Erbrechen, zusätzlich auch Aprepitant. Begonnen wurde 5 Tage vor Chemobeginn, aufgehört 5 Tage nach Ende. Über das Chemoregime wird nicht berichtet. Die Ingwergruppe hatte bedeutsam weniger Übelkeits-Episoden und die Frequenz des Erbrechens war bedeutsam geringer als in der Gruppe, die weder Ingwer noch Kamille erhalten hatte. Die Studie ist nicht gut berichtet, so dass die Vermutung naheliegt, dass die Studie methodisch nicht gut durchgeführt worden ist und die Ergebnisse mit Vorsicht interpretiert werden müssen.

Study Design

Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies	Prospective
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	Monocentric
Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties	Double
Is randomized	Yes
Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control	No
Number of arms	3

Study characteristics

Inclusion criteria	Patients between 20 and 60 years; histological diagnosis of breast cancer, history of receiving at least one chemotherapy injection, receiving single-day cycles of chemotherapy (each cycle separated from next by≥2 weeks); experiencing vomiting in previous sessions, and having normal values of hematologic and biomedical laboratory parameters.
Exclusion criteria	Patients with multiple-day chemotherapy; receiving concurrent radiotherapy with high risk of causing emesis (i.e., total body, hemi body, upper abdomen, and craniospinal radiation); taking therapeutic doses of warfarin, aspirin, or heparin; had a history of bleeding disorder(s) like severe thrombocytopenia; had an allergy to ginger or chamomile or had taken it in the last week; had gastrointestinal disorders and cancers; and had other emesis-inducing diseases, such as hypertension, liver, and renal failure. Further exclusion of patients who met the following criteria: forgotten to take capsules ≥3 consecutive times; used other antiemetic drugs or therapeutic methods except the routine antiemetic; had severe gastrointestinal problems during the study; and refusal to continue participating in trial.
N randomized	65
Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment.	PP Analysis
Specifications on analyses	Chi-squared test, inferential statistics of the linear logarithm model with Poison and paired t-test function
Countries of data collection	Iran
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	NI

Characteristics of participants

Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors.	Curative
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Breast Cancer
Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis	NI
Specifications on cancer stages	NI
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	NI
Previous cancer therapies	Chemotherapy
Gender	Female
Gender specifications	100% female
Age groups	Adults (18+)
Age groups specification	n in the following age groups for ginger vs. chamomile vs. placebo: - 20-30 years: 1/1/1 - 31-40 years: 6/1/6 - 41-50 years: 7/12/7 - 51-60 years: 1/1/1 Range: 20-60 years

Arms

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Intervention
Number of participants (arm) N randomized	23
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	N=8
Drop-out reasons	Not separated by arm: - general weakness + discontinuation of chemotherapy (n=7) - further participation refused (n=6) - non-completion of questionnaires (n=6) - death (n=1)
Intervention	Ginger capsules + Antiemetic treatment (dexamethasone + metoclopramide + aprepitant)
Dosage and regime	Daily dose of 2x500mg ginger capsules (not standardized), from 5 days before chemotherapy until 5 days after chemotherapy
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	10
Side effects / Interactions	NI

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Intervention
Number of participants (arm) N randomized	22
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	N=7
Drop-out reasons	Not separated by arm: - general weakness + discontinuation of chemotherapy (n=7) - further participation refused (n=6) - non-completion of questionnaires (n=6) - death (n=1)
Intervention	Matricaria Chamomilla extract capsules + Antiemetic treatment (dexamethasone + metoclopramide + aprepitant)
Dosage and regime	Daily dose of 2x500mg chamomile capsules (not standardized), from 5 days before chemotherapy until 5 days after chemotherapy
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	10
Side effects / Interactions	NI

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Passive control
Number of participants (arm) N randomized	20
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	N=5
Drop-out reasons	Not separated by arm: - general weakness + discontinuation of chemotherapy (n=7) - further participation refused (n=6) - non-completion of questionnaires (n=6) - death (n=1)
Intervention	TAU (i.e. antiemetic treatment: dexamethasone + metoclopramide + aprepitant)
Dosage and regime	NA
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	-999
Side effects / Interactions	NI

Outcomes

CINV (Chemotherapy-Induced Nausea and Vomiting)

Outcome type As specificed by the authors	NI
Outcome specification	Frequency and severity of nausea and vomiting
Type of measurement	VAS (Visual Analogue Scale), Self-developed measurement instrument
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NA
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	Intensity of nausea No significant difference between arms (p=0.238) Frequency of nausea Significant effects for ginger arm (p=0.013): - significant difference between ginger and chamomile arm (mean (SD): 1.66 (0.53); p=0.002) and ginger and control arm (mean (SD): 1.58 (0.58); p=0.006), no direction indicated - no significant difference between chamomile and control arm (p=0.895) Frequency of vomiting Significant effects for ginger and chamomile arm respectivly (p<0.0001; p=0.02) - significant differences between ginger and control (p>0.0001) and chamomile and control (p=0.003), no direction indicated - no significant difference between ginger and chamomile arm (p=0.177)

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Toxicity

Outcome type As specificed by the authors	Secondary
Outcome specification	NA
Type of measurement	Observation, Self-developed measurement instrument
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NI: data collected but not reported
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	NI

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	?
Bias due to deviation from intended intervention (assignment to intervention)	?
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	?
Bias in measurement of the outcome	?
Bias in selection of the reported result	?
Other sources of bias	?
Overall RoB judgment	?

Funding and Conflicts of Interest

Funding	This study was carried out with the financial support of research deputy of University of Social Welfare and Rehabilitation Sciences and with the favor of Breast Cancer Research Center of University of Tehran.
Conflicts of Interest	NI

Further points for assessing the study

Sample

Power analysis performed	?
- Sample size corresponds to power analysis	?
- Reasons for insufficient sample size based on power analysis	?
If no power analysis performed: at least moderate sample size (n >= 30 per arm)	?
Ethnicity mentioned	?

Alternative Explanation

Other explanations for an effect besides the investigated intervention	?
- Possibility of attention effects	?
- Possibility of placebo effects	?
- Other reasons	?

Statistics

Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing	?
Correction for multiple testing	?
Measurement of compliance	?
Consistent reporting in numbers (figures, flowchart, abstract, results)	?
Comprehensive and coherent reporting	?
Cross-over	?
- Sufficient washout period	?
- Tested for carry-over effects	?
- Tested for sequence effects	?

Interpretation of results

Effect sizes reported (clinical vs. statistical significance)	?
Side effects systematically recorded	?
Side effects considered in result interpretation	?
Ethics votum	?

Additional Notes

• Vomiting severity mentioned as a target parameter in the report but not in the register
• High drop-out rate (n=20)
• Severity of CINV episodes not reported
• AEs not reported
• Tables partly incomprehensible