ONC: Chemotherapy (2006)
- Patients at the Department of Clinical Oncology of the Leiden University Medical Center
- Eligible for cisplatin single agent or combination chemotherapy
Recruitment - 27 consecutive cancer patients at the Department of Clinical Oncology of the Leiden University Medical Center were recruited between February 1995 and August 1997
Design - From the 27 consecutive cancer patients undergoing cisplatin-based combination chemotherapy, 13 were randomized to receive a beverage supplemented with vitamin C, vitamin E and selenium, while the remaining 14 cancer patients received a beverage without vitamins E and C and selenium. Both groups received the beverage 2X day beginning 7 days before onset of chemotherapy until 3 weeks after cessation of therapy. Antioxidant status and genotoxicity status were measured at 10 times during the study
Blinding used (if applicable) - Double blind
Intervention (if applicable) - Beverage containing 1000 mg vitamin C, 400 mg vitamin E and 100 ug selenium
Statistical Analysis -
- Paired Student's t-test used to compare the values of parameters of individual patients during one particular cycle and the values on day 1 of two distinctive cycles
- Independent Student's t-test was used to compare mean values of parameters between both study groups
- Mann-Whitney U-test or chi-square test was used for comparisons between both study groups with respect to categoric parameters.
- Bivariate Pearson's correlation coefficients were used to investigate the relationships between the various parameters concerning antioxidants, oxidative stress or organ dysfunction and those parameters indicating genotoxicity.
- P < 0.05 significance
Timing of Measurements
Inclusion | Cycle 1 | Cycle 2 | Cycle 4 | After chemotherapy | ||||||
Start | Discharge | Nadir | Start | Start | Discharge | Nadir | 2 months | 1 year | ||
Antioxdiant status | X | X | X | X | X | X | X | X | X | X |
Genotoxicity status | X | X | X | X | X |
Nadir = between days 8 and 15 after administration of the first and fourth chemotherapy courses at the outpatient department
Antioxidant status = vitamin C, vitamin E, vitamin E/lipids ratio, selenium and malondialdehyde
Genotoxicity status = Micronuclei frequency and hypoxanthine phosphoribosyl transferase mutant frequency in peripheral blood lymphocytes
Dependent Variables
- Variable 1: Chromosomal damage in peripheral blood lymphocytes (PBLs) measured by scoring MN in binucleate (BN) lymphocytes.
- Variable 2: Hypoxanthine phosphoribosyl transferase (HPRT) mutant frequency measured by clonal assay
- Variable 3: Total vitamin C, vitamin E and malondialdehyde (a product of lipid peroxidation used as a marker of oxidative stress) were measured by HPLC.
- Variable 4: Plasma selenium levels determined by atomic absorption spectoscopy
- Variable 5: Renal function measured using creatinine clearance
- Variable 6: Hearing function measured by audiologic examination
Independent Variables
Antioxidants vitamin C, vitamin E and selenium
Control Variables
Cisplatin based chemotherapy
Initial N: 27; 24 male, 3 female
Attrition (final N): undisclosed
Age: 24 men, range 16-68 y.o; 3 women , range 47-69 y.o.
Ethnicity: not disclosed
Other relevant demographics:
Testicular cancer n= 9
Bladder cancer n = 2
Sarcoma n= 7
Gastric cancer n=5
Head and neck cancer n= 3
Cervical cancer n= 1
Anthropometrics
Micronuclei frequency - increase did not differ between supplemented and placebo patients
Hypoxanthine phosphoribosyl transferase mutants - no consistent change between supplemented and placebo patients
Due to insufficient numbers of patients available for this study, no conclusions could be drawn about the changes in MNF's and HPRT MF's after three chemotherapy cycles
Vitamins C, E and selenium did not protect against genotoxic effects in blood lymphocytes following chemotherapy
Location:
The Netherlands
Variables | Supplemented Group | Placebo Group | Statistical Significance of Difference |
Chromosomal damage | No difference | ||
HPRT | No difference | ||
Plasma antioxidant | No difference | ||
Renal function | No difference | ||
Hearing function | No difference |
Hypoxanthine phosphoribosyl transferase mutants - no consistent change between supplemented and placebo patients
Due to insufficient numbers of patients available for this study, no conclusions could be drawn about the changes in MNF's and HPRT MF's after three chemotherapy cycles
Vitamins C, E and selenium did not protect against genotoxic effects in blood lymphocytes following chemotherapy
Other Findings
- the study confirms the genotoxicity of chemotherapy
- depletion of plasma antioxidant concentrations prior to and after chemotherapy may result in acute and long term organ damage
Industry: |
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University/Hospital: | Leiden University Medical Centre (Netherlands) |
Limitations:
- very small study; cannot be of any signficance
- enrolled patients were first stated as 27, then 25, then 23
- 24 men vs 3 women enrolled
- undisclosed how many smokers were in the supplemented vs placebo group
- compliance was low among supplementation group (at start of second chemotherapy cycle, only 8 out of 13 were compliant)
- more patients in the supplementation group stopped drinking the beverage than in the placebo group
- no conclusions can be drawn about the changes in MNFs and HPRT MFs at time points later then three chemotherapy cycles because of insufficient numbers of patients available for this study
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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? | Yes | |
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? | No | |
2.2. | Were criteria applied equally to all study groups? | Yes | |
2.3. | Were health, demographics, and other characteristics of subjects described? | Yes | |
2.4. | Were the subjects/patients a representative sample of the relevant population? | Yes | |
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) | Yes | |
3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | No | |
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")? | N/A | |
4. | Was method of handling withdrawals described? | No | |
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%.) | No | |
4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | No | |
4.4. | Were reasons for withdrawals similar across groups? | ??? | |
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? | Yes | |
5.1. | In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? | Yes | |
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.) | Yes | |
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? | N/A | |
6. | Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? | No | |
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? | ??? | |
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? | No | |
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? | Yes | |
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)? | Yes | |
8.6. | Was clinical significance as well as statistical significance reported? | No | |
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 | |