Study Note
Brief summary
This study investigated the efficacy of vitamin E in colorectal cancer patients to alleviate chemotherapy-associated peripheral neuropathy (i.e. damage to several peripheral nerves). The intervention arm took additional vitamin E during chemotherapy and the control arm received only a placebo. There were no significant differences in the incidence and severity of peripheral neuropathy between the two study arms. There are numerous points of criticism of this study. For example, the sample was too small to be able to determine the expected effects statistically well. Apart from this, there were possibly other biases that could not be ruled out due to the poor quality of reporting (e.g. no information on the stage of the disease).
In dieser Studie wurde die Wirksamkeit von Vitamin E bei Darmkrebspatienten untersucht, Chemotherapie assoziierte periphere Neuropathie (d.h. Schädigung mehrerer peripherer Nerven) zu lindern. Der Interventionsarm nahm während der Chemotherapie zusätzlich Vitamin E ein und der Kontrollarm bekam nur ein Placebo. Es fanden sich keine signifikanten Unterschiede hinsichtlich der Auftretenshäufigkeit und der Schwere der peripheren Neuropathie zwischen den beiden Studienarmen. An dieser Studie gibt es zahlreiche Kritikpunkte. So war die Stichprobe zu klein, um die erwarteten Effekte statistisch gut feststellen zu können. Abgesehen davon gab es möglicherweise weitere Verzerrungen, die wegen der schlechten Berichtqualität (z.B. keine Angabe zum Krankheitsstadium) nicht ausgeschlossen werden konnten.
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
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Prospective
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| Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals
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Monocentric
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| 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
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No
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| Is randomized
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Yes
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| Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control
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No
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| Number of arms
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2
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Study characteristics
| Inclusion criteria
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18–75 years, diagnosed with colorectal cancer, scheduled to receive oxaliplatin‑based regimens, more than 6 month life expectancy
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| Exclusion criteria
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Previous history of peripheral neuropathy or symptomatic peripheral neuropathy at entry into the study, received other chemotherapy regimens, currently receiving anticoagulants, platelet aggregation inhibitors, opioids, anticonvulsants, tricyclic antidepressants, and previous history of hemorrhagic stroke
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| N randomized
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70
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| 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.
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PP Analysis
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| Specifications on analyses
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NA
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| Countries of data collection
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Iran
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| LoE Level of evidence
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2b Oxford 2009
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| Outcome timeline Data collection times
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Baseline (prior to chemotherapy), prior to every chemotherapy cycle and after 6. chemotherapy cycle
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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.
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NI
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| Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included
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Colorectal Cancer
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| 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
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NI
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| Specifications on cancer stages
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NI
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| Comorbidities
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NI
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| Current cancer therapies
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Chemotherapy
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| Specifications on cancer therapies
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Oxiplatin-based chemotherapy (oxaliplatin + 5‑fluorouracil + leucovorin (FOLFOX4); oxaliplatin: 85 mg/m 2 intravenous [IV] on day 1, 5‑fluorouracil: 400 mg/m 2 IV bolus, followed by 600 mg/m 2 IV continuous infusion for 22 h on days 1 and 2, leucovorin: 200 mg/m 2 IV on days 1 and 2 as a 2‑h infusion before 5‑fluorouracil)
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| Previous cancer therapies
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NI
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| Gender
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Mixed
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| Gender specifications
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36.9% female
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| Age groups
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Adults (18+)
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| Age groups specification
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Mean (SD) = 57.5 (14.0) years
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Arms
| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
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Intervention
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| Number of participants (arm) N randomized
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35
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| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
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3
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| Drop-out reasons
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Patient decision n=2
Other medical problems n=1
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| Intervention
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Vitamin E
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| Dosage and regime
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400 mg daily
Duration: until 6. chemotherapy cycle
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| One-time application
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No
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| 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.
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-999
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| Side effects / Interactions
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NI
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| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
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Passive control
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| Number of participants (arm) N randomized
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35
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| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
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2
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| Drop-out reasons
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Patient decision n=1
Other medical problem n=1
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| Intervention
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Usual Care
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| Dosage and regime
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NA
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| One-time application
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No
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| 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.
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-999
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| Side effects / Interactions
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NI
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Outcomes
<ul><li>"Chemotherapy-induced peripheral neuropathy" 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.</li> <!--br--><li>"Symptom Experience Diary Questionnaire (NCCTG)" is not in the list (AQoL-8D (Assessment of Quality of Life), ASAT (Auditory Sustained Attention Test), BIA (Bioelectrical impedance analysis), BPI-SF (Brief Pain Inventory - Short Form), CTCAE (Common Terminology Criteria of Adverse Events), ESAS (Edmonton Symptom Assessment Scale), FAACT (Functional Assessment of Anorexia-Cachexia Therapy), FACIT (Functional Assessment of Chronic Illness Therapy), FLIE (Functional Living Index for Emesis), Genitourinary atrophy self-assessment tool, ...) of allowed values for the "Type of measurement" property.</li></ul>
Peripheral neuropathy
| Outcome type As specificed by the authors
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Primary
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| Outcome specification
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Symptom experience diary questionnaire developed by NCCTG, range 0-70, peripheral neuropathy, if absolute value > 0
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| Type of measurement
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Symptom experience diary (NCCTG)
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| 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".
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NA
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| 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".
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Overall:
Number in %
Intervention: 100, Control: 96; p = 0.8
Mittelwert (SD):
Intervention: 6.37 (2.85), Control: 6.57 (2.94); p = 0.78
No significant group differences were found when considering gender and age (no numbers reported).
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
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| Bias arising from the randomization process
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?
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| Bias due to deviation from intended intervention (assignment to intervention)
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?
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| Bias due to deviation from intended intervention (adhering to intervention)
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NA
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| Bias due to missing outcome data
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?
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| Bias in measurement of the outcome
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?
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| Bias in selection of the reported result
|
?
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| Other sources of bias
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?
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| Overall RoB judgment
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?
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Funding and Conflicts of Interest
| Funding
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NI
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| Conflicts of Interest
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NI
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Further points for assessing the study
Sample
| Power analysis performed
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?
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| - Sample size corresponds to power analysis
|
|
| - Reasons for insufficient sample size based on power analysis
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| If no power analysis performed: at least moderate sample size (n >= 30 per arm)
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?
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| Ethnicity mentioned
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?
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Alternative Explanation
| Other explanations for an effect besides the investigated intervention
|
|
| - Possibility of attention effects
|
?
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| - Possibility of placebo effects
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?
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| - Other reasons
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?
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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
|
?
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| Measurement of compliance
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?
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| Consistent reporting in numbers (figures, flowchart, abstract, results)
|
?
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| Comprehensive and coherent reporting
|
?
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| Cross-over
|
|
| - Sufficient washout period
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?
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| - Tested for carry-over effects
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?
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| - Tested for sequence effects
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?
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Interpretation of results
| Effect sizes reported (clinical vs. statistical significance)
|
?
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| Side effects systematically recorded
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?
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| Side effects considered in result interpretation
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?
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| Ethics votum
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?
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Additional Notes
