ONC: Chemotherapy (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E (300 mg/day) in patients treated with cisplatin chemotherapy.
Inclusion Criteria:

Patients:

·          Seen between April 1999 and October 2000

·          Solid malignancies

·          Karnofsky Performance Status between 70 to 100

·          Require cisplatin treatment

Exclusion Criteria:

·          No previous chemotherapeutic treatment or regimens including other neurotoxic drugs associated with cisplatin

·          Failure to receive a cumulative dose of cisplatin higher than 300 mg/m2

Description of Study Protocol:

Recruitment

41 patients who met the inclusion criteria

Design

·       Patient selection and randomization

·         Neurological exam for baseline measures

·         Intervention with cisplatin alone or cisplatin with vitamin E

·         Neurological exam for final measures

Blinding used (if applicable)

Patients and investigators were not blinded

Intervention (if applicable) 

Alpha-tocopherol (300 mg/day) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment

 Statistical Analysis

  • Descriptive statistics used to describe the treatment groups
  • Paired t-tests and Wilcoxon sign-rank test used to compare treatment group results 
Data Collection Summary:

Timing of Measurements

·          Baseline

·          After six cycles of cisplatin

Dependent Variables

  • Variable 1: Sural amplitude – electrophysiologic examination
  • Variable 2: Sural sensory conduction velocity (SCV) – electrophysiologic examination
  • Variable 3:  Median amplitude– electrophysiologic examination
  • Variable 4:  Neurotoxicity score – assigned based on neuropathic signs and symptoms (using a questionnaire and on electrophysiologic changes).  Severity of neurotoxicity was graded on the basis of obtained total scores as:
    • Mild = 1 to 4
    • Moderate = 5 to 8
    • Severe = more than 8
    • Score corresponds to World Health Organization neurotoxicity grades 1, 2 and 3-4, respectively

Independent Variables

Alpha-tocopherol (300 mg/day) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment

Control Variables 

Pre and post neurological examinations done by the same neurologist

Description of Actual Data Sample:

Initial N: N=47 patients

Attrition (final N):  N=27 patients (13 supplemented group, 14 control group) (57%)

Characteristics of patients

Characteristics

Group 1 (n=13)

Group 2 (n=14)

Median age years, range

58 (37 to 69)

57 (28 to 74)

Median cisplatin cumulative dose/mq/mL, range

420 (300 to 550)

420 (225 to 600)

Median basal vitamin E (mg/mL), range

8.0 (4.6 to 10.1)

7.2 (3.3 to 9.5)

Response rate, complete response + partial response

61.5%

72.7%

Ethnicity: Not reported

Anthropometrics (e.g., were groups same or different on important measures)

Location: Gallicano Institute, Rome, Italy  

Summary of Results:

 

Group 1

Group 1

Group 2

Group 2

Variables

Basal

After Cisplatin and Vit E

Basal

After Cisplatin

P

Sural amplitude, mean +/-SD

51.2+/-4.1 m/sec

49.6 +/-5.1 uV

48.5 +/-5.6 uV

45 +/-5.9 uV

Sural sensory conduction velocity

15.5+/-6.3uV

15.5+/-6.3uV

15.5+/-6.3uV

15.5+/-6.3uV

<. 01

Median amplitude, mean +/- SD

15.1 +/- 5.2 uV

12 +/- 0.6 uV

15 +/- 9.2 uV

8.7 +/- 5.3 uV

<. 01

Reflexes and distal par4esthesia, no of patients

0 of 13

4 of 13

0 of 14

12 of 14

 

Neurotoxicity score, mean +/- SD

 

2.1 +/- 2.1

 

4.7 +/- 2.9

<. 01

 

·  Incidence of neurotoxicity (i.e., complained of distal paresthesia and presented with a reduction in deep tendon reflexes) was significantly lower in group one, 4 of 13  (30.7%) than it was in group two 12 of 14 (85.7%; P<. 01)

·  The severity of neurotoxicity, measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters, was significantly lower in patients who were supplemented with vitamin E (2 verses 4.7,P<. 01) than in patients not supplemented with vitamin E

·  The relative risk (RR) of developing signs or symptoms of neurotoxicity was significantly lower in group one than it was in group two (RR = 0.36; 95% CI = 0.15 to 0.83; P < .001)

·  No significant difference between the two groups was observed in either clinical response or in systemic toxicities

 

 

Author Conclusion:
This research indicates that vitamin E supplementation significantly protects against cisplatin-induced peripheral neurotoxicity and reduces the incidence and intensity of neuropathic signs and symptoms.
Funding Source:
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:

·          Large attrition rate (57%)

·          Small sample size

·          No placebo was used

·          No blinding was used

·          Intention to treat analysis of the entire study population could not be achieved because of attrition

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? No
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? No
  2.4. Were the subjects/patients a representative sample of the relevant population? No
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? No
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? No
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? ???
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? ???
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  6.6. Were extra or unplanned treatments described? No
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? No
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? No
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? ???
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes