Ansari et al. (2016): Efficacy of Ginger in Control of Chemotherapy Induced Nausea and Vomiting in Breast Cancer Patients Receiving Doxorubicin- Based Chemotherapy

Reference ↗
Title	Efficacy of Ginger in Control of Chemotherapy Induced Nausea and Vomiting in Breast Cancer Patients Receiving Doxorubicin- Based Chemotherapy
Topic	Ginger
Author	Ansari, M, Porouhan, P, Mohammadianpanah, M, Omidvari, S, Mosalaei, A, Ahmadloo, N, Nasrollahi, H, Hamedi, SH
Year	2016
Journal	Asian Pacific Journal of Cancer Prevention
DOI	https://doi.org/10.14456/apjcp.2016.186/APJCP.2016.17.8.3877

Brief summary

150 breast cancer patients were randomly divided into two arms. One arm received 1000mg of ginger powder (not standardized) daily for 3 days during chemotherapy, the other arm received a placebo. The chemotherapy regime was strongly nausea- and vomiting-promoting. All patients were also given additional anti-nausea medication, including aprepitant. There were no arm differences, i.e. ginger was not superior to placebo, but one subarm benefited: the patients who received the chemotherapy regime doxorubicin 60 mg/m² + cyclo-phosphamide 600 mg/m² suffered significantly less vomiting when they took ginger. Adverse 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.

150 Brustkrebspatientinnen wurden zufällig in zwei Gruppen geteilt. Die eine Gruppe erhielt über 3 Tage während der Chemo täglich 1000mg Ingwerpulver (nicht standardisiert hergestellt), die andere Gruppe erhielt ein Plazebo. Das Chemoregime war stark Brechreiz- und Übelkeit-fördernd. Allen Patientinnen wurde auch noch zusätzliche Medikamente gegen die Übelkeit gegeben, u.a. Aprepitant. Es gab keine Gruppenunterschiede, d.h. Ingwer war dem Plazebo nicht überlegen, allerdings profitierte eine Untergruppe: Die Patientinnen, die das Chemoregime Doxorubicin 60 mg/m² + Cyclo-phosphamid 600 mg/m² erhielten, litten bedeutsam unter weniger Erbrechen, wenn sie Ingwer eingenommen hatten. Unerwünschte 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	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	2

Study characteristics

Inclusion criteria	Patients who were pathologically diagnosed with breast cancer, receiving AC, CAF or TAC chemotherapy regimen, receiving at least 3 chemotherapy cycles
Exclusion criteria	History of previous malignancy or chemotherapy, history of other systemic diseases, metastatic condition or receiving other antiemetic drugs
N randomized	150
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- square test, independent T-test and Mann-Whitney test
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	Chemotherapy regimens (n intervention vs. placebo arm): - AC, i.e. doxorubicin60 mg/m2 +cyclophosphamid 600 mg/m2 (41 vs. 44) - CAF, i.e. cyclophosphamide 500mg/m2 + doxorubicin 50mg/ m2 + 5-Fluorouracil 500mg/m2 (19 vs. 18) - TAC, i.e. docetaxel 75mg/m2 + doxorubicin 50mg/m2 + cyclophosphamide 500mg/m2 (15 vs. 13)
Previous cancer therapies	NI
Gender	Female
Gender specifications	100% female
Age groups	Adults (18+)
Age groups specification	Mean (range) in years: 48.6 (25-79)

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	75
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	N = 18
Drop-out reasons	Forms not filled out correctly
Intervention	Ginger capsules + Antiemetic treatment: dexamethasone, aprepitant, granisetron (before each cyle + first two days of each cyle)
Dosage and regime	Daily dose 2x2 ginger capsules (250mg ginger powder each), every 12h for 3 days over 3 cycles, start not specified
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	No ginger related side effects were reported.

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Placebo
Number of participants (arm) N randomized	75
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	N = 13
Drop-out reasons	Forms not filled out correctly
Intervention	Placebo capsules + Antiemetic treatment: dexamethasone, aprepitant, granisetron (before each cyle + first two days of each cyle)
Dosage and regime	Daily dose 2x2 capsules, every 12h for 3 days over 3 cycles, start not specified
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

Nausea

Outcome type As specificed by the authors	NI
Outcome specification	Nausea severity
Type of measurement	Diary questionnaire, CTCAE (Common Terminology Criteria of Adverse Events)
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".	Nausea (all three cycles): no significant difference for mean nausea in ginger vs. placebo arm Subgroup analysis for different chemotherapies: no significant arm differences
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

Vomiting

Outcome type As specificed by the authors	NI
Outcome specification	Vomiting severity
Type of measurement	Diary questionnaire, CTCAE (Common Terminology Criteria of Adverse Events)
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".	Vomiting (all three cycles): no significant between arms Among participants with the Chemotherapy regimen AC (doxorubicin+cyclophosphamide) in intervention arm significantly lower severity of vomiting than in placebo arm, mean (SD): 0.64 (0.87) vs. 1.13 (1.12), p<0.05

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

Funding and Conflicts of Interest

Funding	University of Medical Sciences supported this study
Conflicts of Interest	NI

Further points for assessing the study

Sample

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

Alternative Explanation

Other explanations for an effect besides the investigated intervention	Yes
- Possibility of attention effects	No
- Possibility of placebo effects	No
- Other reasons	Significant effect in supgroup analysis possibly due to multiple testing + possibility of baseline differences

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	NI
Correction for multiple testing	No
Measurement of compliance	Yes
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	NI
Side effects considered in result interpretation	Yes
Ethics votum	NI

Additional Notes

Adherence intervention-arm vs. placebo-arm: 76 % vs. 82 %