ONC: Dietary Supplements and Medical Food Supplements Containing Fish Oil (2013)
Read JA, Beale PJ, Volker DH, Smith N, Childs A, Clarke SJ. Nutrition intervention using an eicosapentaenoic acid (EPA)-containing supplement in patients with advanced colorectal cancer. Effects on nutritional and inflammatory status: a phase II trial. Support Care Cancer. 2007 Mar; 15(3): 301-307. Epub 2006 Oct 5.PubMed ID: 17021855
To assess the effects of nutritional counseling and provision of an EPA-oral nutrition supplement (ONS) on nutritional status, body composition, QOL, plasma phospholipids, C-reactive protein, cytokines and chemotherapy toxicity in patients with advanced colorectal cancer receiving irinotecan.
Patients with histologically confirmed diagnosis of stage IV colorectal cancer were eligible for study recruitment. Other eligibility criteria included:
- WHO performance status of zero to two
- No chemotherapy in the previous four weeks
- No surgery for the past two weeks
- Body mass index less than 35kg/m2
- Adequate hematological, renal and hepatic status
- Bi-dimensionally measurable disease
- Estimated life-span more than three months.
- Previously received irinotecan
- Pre-existing intestinal disease
- Psychiatric disorders
- Unable to take an oral intake.
Patients were recruited from an open label phase II study conducted between August 2002 and January 2005 at the Royal Prince Alfred and Concord Hospitals in Sydney, Australia.
Prospective cohort study.
Patients were instructed to consume, in addition to their regular diet, two tetrapaks (480ml) per day of an EPA-ONS (EPA-Oral Nutritional Supplement) for nine weeks.
- SPSS version 11.5 was used for all statistical analysis
- Non-parametric Wilcoxon signed ranks test was performed to determine changes in nutritional status, inflammatory status, cytokines and QOL parameters
- Statistical significance was reported at P<0.05
- Pearson's correlations were performed between cytokine levels at baseline and survival, chemotherapy toxicity and various nutritional and inflammatory markers.
Timing of Measurements
All measurements were taken at baseline and again at the end of weeks three and nine to correlate with chemotherapy treatments.
- Nutritional status: Measured by the patient-generated subjective global assessment (PG-SGA)
- Weight: Measured with spring balance scale
- Lean body mass: Measured with a single frequency four-terminal bio-impedance meter; fat-free mass, fat mass and total body water were calculated according to the Lukaski algorithm and fat-free mass was used as the measure of lean body mass
- Quality of Life: Fatigue, appetite, nausea, vomiting, diarrhea, energy level, physical and overall well-being with the disease and treatment assessment (DATA) form
- Plasma Phospholipids: EPA, DHA, arachidonic acid; Interleukins and RANTES (a beta-chemokine) using standard methods
- Total energy and protein intake: analyzed by three-day food records using FoodWorks professional edition 3.02.
Consumption of two tetrapaks (480ml) of EPA-ONS (oral nutritional supplement) for nine weeks (ProSure by Abbott Laboratories).
- Initial N: 23 patients (15 male, eight female)
- Attrition (final N): 15
- Age: Median age was 61±11.6.
- Baseline weight: 75.9kg
- Baseline C-reactive protein: 18.2mg per L
- Baseline lean body mass: 50.3kg
- Baseline nutritional status per SGA: A=11, B=11, C=1
- Baseline nutritional status per PG-SGA score: Seven (requires intervention by a dietitian).
Royal Prince Alfred and Concord Hospitals in Sydney, Australia.
- 23 patients began the study; 20 patients completed three weeks and 15 continued to take the EPA-ONS until the end of the study period. 18 patients completed three chemotherapy cycles, including 15 patients who continued to take the EPA-ONS. Three patients ceased taking the EPA-ONS due to intolerance (N=2) and disease progression (N=1). Seven patients had a chemotherapy dose reduction. The average intake of the EPA-ONS at the end of trial was 1.7 tetrapaks (408ml).
- Reasons for patient withdrawal included:
- Intolerance to the EPA-ONS (N=2)
- Disease progression (N=4)
- Admission to hospital with head injury (N=1)
- Severe toxicity to chemotherapy (N=1).
- Of the 23 patients that began the trial:
- 16 tolerated the EPA-ONS well
- One experienced loss of appetite
- One had stomach distension
- One had nausea
- Two experienced vomiting
- Two disliked the taste of the supplement.
- 12 patients presented with a degree of malnutrition and were classified in the B or C category using the PG-SGA, while 11 (48%) patients had no significant weight loss and were classified as well-nourished. A mean PG-SGA score of 7.5 was recorded at baseline.
- Mean weight increased by 2.5kg from baseline to the end of week three (P=0.03) and remained stable during the chemotherapy phase of the study. No significant changes were noted in lean body mass or PG-SGA scores.
- C-reactive protein increased significantly between baseline and week three (P=0.004); however, it decreased significantly to baseline levels during chemotherapy between weeks three and nine (P=0.02)
- Significant decrease in both total and meal energy (P=0.02, P-0.04) and protein (P=0.003, P-0.01) intake when comparing the first week of taking the supplement and week four, when chemotherapy began
- Total and meal energy intake improved by the end of the study with no significant change from baseline levels
- Energy levels increased between end of weeks three and nine (P=0.03) but all other quality of life measures were maintained. The quality of life for overall well-being showed a trend towards improvement during the full course of therapy (P=0.05).
- Patients' dietary intake of n-3 fatty acids increased at week three and was maintained through to week nine. No significant change in n-6 fatty acid intake was seen.
- Of the 15 patients that took the EPA-ONS, only two patients (13%) experienced grade three diarrhea
- Plasma phospholipids fatty acids from baseline to weeks three and nine; EPA levels significantly increased over the study period from 0.53% to 5.3% at the end of week three remaining high at 4.8% by the end of week nine (P=0.002). DHA increased significantly from 2.6% to 7.04% between baseline and the end of week three (P=0.005), remaining high with a recording of 6.8% at the end of week nine. Arachidonic acid decreased from a baseline of 7.7% to 7.2% at week three, and was similar at the end of week nine.
- Only three of the 16 recorded cytokines changed in a statistically significant manner during the trial (Eotaxin, GM-CSF and RANTES). A significant correlation was seen between survival median values at baseline for IL-10 (P=0.03, R=0.488) and IL-6 (P=0.003, R=0.63) and between toxicity and IL-12 at baseline (P=0.023, R=0.533). There was a significant correlation between baseline C-reactive protein level and IL-6 (P=0.004, R=0.609).
- The results clearly demonstrate that patients were able to improve or maintain weight and lean body mass while taking the EPA-ONS in association with counseling from a suitably qualified dietitian
- The plasma phospholipids EPA incorporation increased significantly after three weeks of EPA-ONS and was maintained throughout the study period. This effect was attributed to the dietary advice provided by the experienced dietitian.
- A greater percentage of patients who did not comply with taking the EPA-ONS, experienced grade three diarrhea compared to those who did comply
- Over time there was no significant change between both the total energy intake and the meal energy intake between baseline and the end of trial
- There was little change in cytokines between the three different time points, except for eotaxin, GM-CSF and RANTES. These changes were not large, although statistically significant, and are unlikely to be clinically relevant.
- All the measures of quality of life were either maintained or improved in this study, but this requires evaluation in randomized trials
In summary, dietary counseling by suitably qualified dietitians and the provision of the EPA-ONS in patients with advanced C-reactive protein receiving FOLFIRI helps to maintain weight and possibly improve symptom control, nutritional status and quality of life. This study demonstrates that with sufficient dietary counseling and support, good patient compliance can be achieved in trials of nutritional supplementation.
|University/Hospital:||Xingying Weng; Westmead Hospital; Sydney Universiy Humn Nutrition unit and t Flinder's Medical Centr Child Nutrition Research Center|
- No clear association between counseling from a qualified dietitian and outcomes was demonstrated
- No details of dietary counseling or dietitian involvement was mentioned
- Bias and limitations were not clearly addressed
- Possible conflict of interest since researchers supplied the supplements.
Quality Criteria Checklist: Primary Research
|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)||N/A|
|2.||Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?||N/A|
|3.||Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?||N/A|
|4.||Is the intervention or procedure feasible? (NA for some epidemiological studies)||N/A|
|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?||Yes|
|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?||Yes|
|3.1.||Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)||N/A|
|3.2.||Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?||N/A|
|3.3.||Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)||N/A|
|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?||Yes|
|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?||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.)||Yes|
|5.3.||In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?||No|
|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?||Yes|
|6.1.||In RCT or other intervention trial, were protocols described for all regimens studied?||N/A|
|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?||Yes|
|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?||N/A|
|6.6.||Were extra or unplanned treatments described?||N/A|
|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?||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)?||N/A|
|8.5.||Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?||N/A|
|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?||???|
|9.||Are conclusions supported by results with biases and limitations taken into consideration?||No|
|9.1.||Is there a discussion of findings?||Yes|
|9.2.||Are biases and study limitations identified and discussed?||No|
|10.||Is bias due to study's funding or sponsorship unlikely?||No|
|10.1.||Were sources of funding and investigators' affiliations described?||Yes|
|10.2.||Was the study free from apparent conflict of interest?||No|