Shamsaei et al. (2017): The Vitamin E Preventive Effect on Taxol-Induced Neuropathy Among Patients With Breast Cancer: A Randomized Clinical Trial

Reference ↗
Title	The Vitamin E Preventive Effect on Taxol-Induced Neuropathy Among Patients With Breast Cancer: A Randomized Clinical Trial
Topic	Vitamin E
Author	Shamsaei G, Ahmadzadeh A, Mehraban N
Year	2017
Journal	Jundishapur Journal Of Natural Pharmaceutical Products
DOI	https://doi.org/10.5812/jjnpp.65027

Brief summary

This study investigated the efficacy of vitamin E in mitigating chemotherapy-induced peripheral polyneuropathy (i.e. damage to multiple peripheral nerves). Two arms of breast cancer patients were studied, one arm taking vitamin E daily in addition to chemotherapy and one arm receiving placebo instead. No differences were found in the electrophysiological function of the tibial nerve (N. tibialis) and the peroneal nerve (N. peroneus). Only in the calf nerve (sural nerve) was the measured amplitude deterioration before and after chemotherapy significantly lower in the vitamin E arm than in the control arm, indicating a lower decrease in the functional capacity of this nerve in the vitamin E arm. Points of criticism of this study are the unclear blinding and the fact that a large number of individual tests were carried out.) Apart from this, further biases cannot be ruled out due to the poor report quality (e.g. no information on the failure rate during the course of the study).

In dieser Studie wurde die Wirksamkeit von Vitamin E untersucht, chemotherapie-induzierte periphere Polyneuropathie (d.h. Schädigung mehrerer peripherer Nerven) abzumildern. Betrachtet wurden zwei Arme von Mammakarzinompatientinnen, von denen eine Arm zusätzlich zur Chemotherapie täglich Vitamin E einnahm und ein Arm stattdessen Placebos bekam. Keine Unterschiede fanden sich hinsichtlich der elektrophysiologischen Funktion des Schienbeinnervs (N. tibialis) und des Wadenbeinnervs (N. peroneus). Nur beim Wadennerv (N. suralis) war die gemessenen Amplitudenverschlechterung vor und nach der Chemotherapie in der Vitamin E Gruppe bedeutsam geringer als in der Kontrollgruppe, was auf eine geringere Abnahme der Funktionsfähigkeit dieses Nervs in der Vitamin E Gruppe hindeutet. Kritikpunkte dieser Studie sind die unklare Verblindung und dass sehr viele Einzeltests durchgeführt wurden). Abgesehen können weitere Verzerrungen wegen der schlechten Berichtqualität (z.B. keine Angabe zur Ausfallrate im Laufe der Studie) nicht ausgeschlossen werden.

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	Single
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	Normal renal and hepatic function, life expectancy of more than one year
Exclusion criteria	History of peripheral neuropathy and systemic diseases such as diabetes mellitus, systemic lupus erythematosus, HIV, and alcohol problems, as well as those with a history of chemotherapy treatment
N randomized	70
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.	ITT Analysis
Specifications on analyses	ITT not specified, but no drop-out reported.
Countries of data collection	Iran
LoE Level of evidence	1b Oxford 2009
Outcome timeline Data collection times	T0: Baseline (prior to chemotherapy) T1: 3 months after chemotherapy

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	Taxol-based chemotherapy
Previous cancer therapies	NI
Gender	Female
Gender specifications	NA
Age groups	Adults (18+)
Age groups specification	Mean (SD) = 47.3 (13.1) 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	35
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	NI
Drop-out reasons	NI
Intervention	Vitamin E
Dosage and regime	Oral, 400 IU daily Duration: length of study
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

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	35
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	NI
Drop-out reasons	NI
Intervention	Placebo
Dosage and regime	Oral, 400 IU daily Duration: length of study
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

Peripheral neuropathy

Outcome type As specificed by the authors	Primary
Outcome specification	N. tibialis, peroneus und suralis
Type of measurement	Electrophysiological evaluation
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".	Mean (SD) Baseline - 3 months after chemotherapy N. tibialis and N. peroneus: No significant differences in amplitude, latency, and conduction velocity (p > 0.05) N. suralis: Amplitude: Intervention: 5.5 (2.4), Placebo: 3.82 (1.8); p < 0.01, sign. Latency, conduction velocity: ns.

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	According to authors none.
Conflicts of Interest	According to authors none.

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

PRO:

• Ethical approval obtained.
• Adequate sample size according to power analysis.

CONTRA:

• Unclear blinding (only mentioned that the nurse distributing the medication is blinded).
• No information on compliance.
• Multiple testing.
• Poor reporting quality (e.g., no information on dropout, no information on important baseline characteristics).