Reference ↗
Title	Oral Intake of Ginger for Chemotherapy-Induced Nausea and Vomiting Among Women With Breast Cancer
Topic	Ginger
Author	Arslan, M, Özdemir, L
Year	2015
Journal	Clinical Journal of Oncology Nursing
DOI	https://doi.org/10.1188/15.CJON.E92-E97

Study Note

Brief summary

In this randomized, controlled study, 60 breast cancer patients received either an additional 500mg of ginger powder (not standardized, mixed with yoghurt) or chemotherapy alone. The first dose was taken 30 minutes before the start of chemotherapy and was then continued over the 3 days of the cycle. Both arms were given other standard anti-nausea and anti-vomiting medications, including aprepitant. The combination of chemotherapy regimens that the patients received caused severe nausea/vomiting. From the second day of treatment, the ginger arm had significantly less nausea/vomiting than the arm without this additive, and the severity was also lower. Side effects were not reported. The study is not well reported, suggesting that the study was not methodologically well conducted and the results must be interpreted with caution.

In dieser randomisiert, kontrollierten Studie erhielten 60 Brustkrebspatientinnen entweder zusätzlich 500mg Ingwerpulver (nicht standardisiert hergestellt, mit Joghurt vermischt) oder nur Chemotherapie. Die erste Einnahme erfolgte 30 Minuten vor Chemostart und wurde dann über die 3 Zyklustage fortgesetzt. Für beide Gruppen gab es weitere Standardmedikamente gegen Übelkeit und Erbrechen, u.a. auch Aprepitant. Die Kombination des Chemoregimes, das die Patientinnen erhielten, ruft starke Übelkeit/Erbrechen hervor. Ab dem zweiten Einnahmetag hatte die Ingwergruppe signifikant weniger Übelkeit/Erbrechen als die Gruppe ohne diesen Zusatz, auch die Stärke war geringer. Nebenwirkungen sind nicht berichtet. 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	No
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	2

Study characteristics

Inclusion criteria	Female with stage II or III breast cancer, having received previous surgical treatment for breast cancer, currently receiving chemotherapy with adjuvant anthracycline (chemotherapy protocols: anthracycline, cyclophosphamide [Cytoxan®], doxorubicin [Adriamycin®], and 5-ﬂuorouracil [Adrucil®]), receiving palonosetron-aprepitant antiemetic treatment, being at least in the second cycle of chemotherapy, and having experienced chemotherapy-induced nausea with a severity of 3 or higher during the previous cycles
Exclusion criteria	NI
N randomized	60
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.	NI
Specifications on analyses	Only included participants (n=60) reported, NI regarding number of randomized patients
Countries of data collection	Turkey
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	T1: Day 1 (i.e. day of the chemotherapy infusion) T2: Day 2 (i.e. day after chemotherapy infusion) T3: Day 3 T4: Day 4 T5: Day 5

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, Adjuvant
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	Early Stage, Advanced Stage
Specifications on cancer stages	Stage II or III breast cancer, no significant differences between arms in cancer stage (p > 0.05)
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	Chemotherapy with adjuvant anthracycline (chemotherapy protocols: anthracycline, cyclophosphamide, doxorubicin, and 5-ﬂuorouracil), no significant differences between arms in chemotherapy characteristics (p > 0.05)
Previous cancer therapies	Surgery
Gender	Female
Gender specifications	100% female
Age groups	Adults (18+)
Age groups specification	Mean: 48.5 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	30
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	Only included participants (n=30) reported, NI regarding number of randomized patients or drop-out
Drop-out reasons	NA
Intervention	Powered ginger + Antiemetic treatment: palonosetron, dexamethasone, an antihistamine, ranitidine, aprepitant
Dosage and regime	Daily dose 2x500mg ginger powder with a spoonful of yogurt for 3 days, first dose 30min before start of 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.	3
Side effects / Interactions	No side effects reported

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	30
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	Only included participants (n=30) reported, NI regarding number of randomized patients or drop-out
Drop-out reasons	NA
Intervention	TAU (treatment as usual), i.e. antiemetic treatment: palonosetron, dexamethasone, an antihistamine, ranitidine, aprepitant
Dosage and regime	NI
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	NA

Outcomes

CINV (Chemotherapy-Induced Nausea and Vomiting)

Outcome type As specificed by the authors	NI
Outcome specification	Nausea severity
Type of measurement	VAS (Visual Analogue Scale)
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".	Daywise comparison At T2 (day2)-T5 (day 5) intervention arm significantly less nausea than control arm, VAS mean (SD) for intervention vs. control: T2 (day 2): 3.8 (1.9) vs. 6.3 (1.9), p<0.001 T3 (day 3): 3.8 (1.8) vs. 6.5 (1.8), p=0.001 T4 (day 4): 3.7 (1.9) vs. 6.3 (1.8), p=0.001 T5 (day 5): 2.8 (1.7) vs. 5.4 (2.3), p=0.001; no significant difference for T1 (day 1) (p=0.15) Mean after intervention Intervention arm significantly less nausea than control arm, VAS mean (SD) for intervention vs. control: 3 (1.5) vs. 5.1 (1.5), p<0.001
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".	Acute and delayed nausea Severity lower in intervention arm than in control arm, VAS mean (SD) for intervention vs. coontrol: - acute: 1.6 (1.1) vs. 3.9 (1.6), p<0.001 - delayed: 3.6 (1.8) vs. 6.1 (1.7), p<0.001

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

CINV (Chemotherapy-Induced Nausea and Vomiting)

Outcome type As specificed by the authors	NI
Outcome specification	Frequency of vomiting
Type of measurement	Diary questionnaire
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".	Daywise comparison At T2 (day2), T3 (day 3) and T5 (day 5) intervention arm significantly less frequent vomiting than control arm, Number of vomiting episodes mean (SD) for intervention vs. control: T2 (day 2): 0 (0.1) vs. 0.3 (0.6), p=0.01 T3 (day 3): 0 (0.1) vs. 0.2 (0.4), p=0.01 T5 (day 5): 0 (0) vs. 0.2 (0.4), p=0.04; no significant difference for T1 (day 1) or T4 (day 4) (p=0.21 and 0.07) Mean after intervention Intervention arm significantly less frequent vomiting than control arm, number of vomiting episodes mean (SD) for intervention vs. control: 0 (0) vs. 0.2 (0.3), p=0.011
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	low risk
Bias due to deviation from intended intervention (assignment to intervention)	high risk
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	high risk
Bias in measurement of the outcome	some concerns
Bias in selection of the reported result	low risk
Other sources of bias	NA
Overall RoB judgment	high risk

CINV (Chemotherapy-Induced Nausea and Vomiting)

Outcome type As specificed by the authors	NI
Outcome specification	Frequency of retching
Type of measurement	Diary questionnaire
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".	Daywise comparison No significant arm difference at all time points: Day 1: p=0.08 Day 2: p=0.29 Day 3: p=0.17 Day 4: p= 0.16 Day 5: p=0.42 Mean after intervention No significant difference in number of retching episodes, p=0.141
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	low risk
Bias due to deviation from intended intervention (assignment to intervention)	high risk
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	high risk
Bias in measurement of the outcome	some concerns
Bias in selection of the reported result	low risk
Other sources of bias	NA
Overall RoB judgment	low risk

Funding and Conflicts of Interest

Funding	NI
Conflicts of Interest	According to authors no conflicts of interest

Further points for assessing the study

Sample

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

Alternative Explanation

Other explanations for an effect besides the investigated intervention	Yes
- Possibility of attention effects	Possibly during first administration of ginger under researcher’s supervision
- Possibility of placebo effects	Yes due to lack of placebo arm
- Other reasons	No

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	Yes
Correction for multiple testing	No
Measurement of compliance	No
Consistent reporting in numbers (figures, flowchart, abstract, results)	Yes
Comprehensive and coherent reporting	No
Cross-over	No
- Sufficient washout period	NA
- Tested for carry-over effects	NA
- Tested for sequence effects	NA

Interpretation of results

Effect sizes reported (clinical vs. statistical significance)	No
Side effects systematically recorded	No
Side effects considered in result interpretation	Yes
Ethics votum	Yes

Additional Notes