ONC: Chemotherapy (2006)
Patients:
· Seen between April 1999 and October 2000
· Solid malignancies
· Karnofsky Performance Status between 70 to 100
· Require cisplatin treatment
· 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 |
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
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
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
|
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
Not-for-profit |
|
· 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
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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 | |