Shokri et al. (2017): Comparison of the Complications of Platinum-Based Adjuvant Chemotherapy With and Without Ginger in a Pilot Study on Ovarian Cancer Patients

Reference ↗
Title	Comparison of the Complications of Platinum-Based Adjuvant Chemotherapy With and Without Ginger in a Pilot Study on Ovarian Cancer Patients
Topic	Ginger
Author	Shokri, F, Mostafa Gharebaghi, P, Esfahani, A, Sayyah-Melli, M, Jafari Shobeiri, M, Ouladsahebmadarek, E, Ghojazadeh, M
Year	2017
Journal	International Journal of Woman's Health and Reproduction Sciences
DOI	https://doi.org/10.15296/ijwhr.2017.55

Brief summary

49 patients with ovarian cancer were treated with cisplatin-based chemotherapy after their surgery (6 cycles). They were randomly divided into two arms, one arm received 2g ginseng (in capsules) per day in addition to chemotherapy, the other arm received no additional therapy. The target parameters were changes in the glycoprotein CA125, metastasis formation, side effects of chemotherapy and the survival rate after 12 months. It was found that there were no significant differences in any of the parameters between the arms. The study is not well reported, so it is reasonable to assume that the study was not methodologically well conducted and the results must be interpreted with caution.

49 Patientinnen mit Eierstockkrebs wurden nach ihrer OP mit Cisplatin-basierter Chemotherapie behandelt (6 Zyklen). Es wurden per Zufallsgenerator in zwei Gruppen geteilt, die eine Gruppe erhielt zusätzlich zur Chemotherapie pro Tag 2g Ginseng (in Kapseln), die andere Gruppe keine zusätzliche Therapie. Zielparameter waren Veränderungen des Glykoproteins CA125, Metastasenbildung, Nebenwirkungen der Chemotherapie und die Überlebensrate nach 12 Monaten. Es zeigte sich, dass sich bei allen Parametern zwischen den Gruppen keine bedeutsamen Unterschiede entstanden waren. Die Studie ist nicht gut berichtet, so dass die Vermutung nahe liegt, 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	?
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	Multicentric
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	Females with approved ovarian cancer who underwent primary cytoreductive surgery, willingness to participate in the study.
Exclusion criteria	The exclusion criteria included allergy to ginger, history of chemotherapy, history of other malignancy in women, reception of vitamin E and omega-3 before or concurrent with chemotherapy, chemotherapy intolerance and patients with stage 4 ovarian cancer.
N randomized	49
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	Kolmogorov-Smirnov test, T-test
Countries of data collection	Iran
LoE Level of evidence	Level 2 Oxford 2011
Outcome timeline Data collection times	T0: baseline T1: after 3 months T2: after 6 months T3: after 9 months T4: after 12 months

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	Gynecologic Cancers - Ovarian 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 I or II
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	Patients who underwent cytoreductive surgery followed by platinum-based adjuvant chemotherapy
Previous cancer therapies	Surgery
Gender	Female
Gender specifications	100 % female
Age groups	Adults (18+)
Age groups specification	(Mean±SD): Intervention: 52.70±10.55, Placebo: 52.69±15.56 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	20
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	N=0
Drop-out reasons	NA
Intervention	Ginger capsules
Dosage and regime	Daily dose 2x 1g ginger capsules for 6 cycles
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	Nausea and vomiting: n=8; Weight loss: n=1; Peripheral neuropathy: n=3; Bone Marrow depression: n=2; Transient Cortical Blindness: n=1; Any other hematologic, renal and digestive complication: n=10 No side effects were reported regarding the ginger intervention.

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	29
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	N=0
Drop-out reasons	NA
Intervention	Placebo-capsules
Dosage and regime	Daily dose 2x 1g placebo capsules for 6 cycles
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	Nausea and vomiting: n=14; Weight loss: n=1; Peripheral neuropathy: n=5; Bone Marrow depression: n=2; Any other hematologic, renal and digestive complication: n=21

Outcomes

"Serum level" is not in the list (Anorexia/Cachexia, Anxiety, Appetite, Cerebral oedema, Cognitive functioning, Cognitive impairment, Depression, Dermatitis, Distress, Dysgeusia, ...) of allowed values for the "Outcome name" property.

Tumor progression

Outcome type As specificed by the authors	Primary
Outcome specification	Results of CT scans in terms of the presence of metastasis at different times
Type of measurement	Observation
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".	Metastases on CT scan: At T0 (Baseline), T2 (after 6 months) metastases significantly less frequent in intervention-arm than in placebo-arm T0 (Baseline) intervention-arm vs. placebo-arm: 45% vs. 72.4% (p=0.05 ) T2 (after 6 months) intervention-arm vs. placebo-arm: 25% vs. 55.2% (p=0.04) No significant difference between arms at the other time points. Mortality: no significant difference between arms (p=0.68) Unfavorable prognosis: Unfavorable prognosis significantly less frequent in intervention-arm than in placebo-arm. OR=3.3 p=0.04

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	?

DFS (Disease-Free Survival)

Outcome type As specificed by the authors	Secondary
Outcome specification	Disease-free 12-month survival:
Type of measurement	Observation
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".	No significant difference between arms (p=0.55)

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	Adverse effects
Type of measurement	Observation
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".	Overall: Nausea / vomiting: intervention-arm: 8, placebo-arm: 14 participants (p=0.57) Weight loss: intervention-arm: 1, placebo-arm: 1 participant (p=0.66) Peripheral neuropathy: intervention-arm: 3, placebo-arm: 5 participants (p=0.58) Bone marrow depression: intervention-arm: 2, placebo-arm: 2 participants (p=0.54) Temporary cortical blindness: intervention-arm: 1, placebo-arm: 0 participants (p=0.41) Other side effects: intervention-arm: 10, placebo-arm: 21 participants (p= 0.11) No significant differences between arms

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	Public funding “Women's Reproductive Health Research Center, Tabriz University of Medical sciences”
Conflicts of Interest	No conflicts of interests.

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	?