EAL

ONC: Dietary Supplements and Medical Food Supplements Containing Fish Oil (2013)

Citation:

Fearon KC, Barber MD, Moses AG, Ahmedzai SH, Taylor GS, Tisdale MJ, Murray GD. Double-blind, placebo-controlled, randomized study of eicosapentaenoic acid diester in patients with cancer cachexia. J Clin Oncol. 2006 Jul 20; 24(21): 3,401-3,407.

PubMed ID: 16849754

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To examine the effects of two doses (2g per day and 4g per day) of a 95% pure Eicosapentaenoic acid (EPA) diester against placebo over a period of at least eight weeks on the process of cachexia in a randomized study.

Inclusion Criteria:

Provided written informed consent
Between the ages of 18 and 80 years with 5% or more loss of pre-illness stable weight
Clinical diagnosis of gastrointestinal and lung cancer (radiological, histologic, cytological confirmation)
Patients had a life expectancy of two months or longer and a Karnofsky performance status of 70 or higher.

Exclusion Criteria:

Receiving ongoing antineoplastic therapy including chemotherapy
Undergone major surgery, chemotherapy or radiotherapy in the previous four weeks
Current or incipient dysphagia or obstruction to the GI tract
Concomitant treatment with fish oil supplements, systemic steroid therapy, nystatin or metronidazole
Non-steroidal anti-inflammatory drug therapy (NSAID) use was also recorded.

Description of Study Protocol:

Recruitment

Patients were recruited from 61 primary treatment centers located in four different countries.

Design

Double-blind, placebo-controlled randomized study.

Blinding used

Double-blind study.

Intervention

Patients were randomly assigned to one of three interventions (either 2g EPA 95% diester per day, 4g EPA diester per day or placebo)
Patients were requested to take the relevant dose as two capsules twice daily for a period of eight weeks.

Statistical Analysis

Two populations were determined for the efficacy of this analysis: An intention-to-treat population containing all of those with details of survival or body weight post-baseline who consumed at least one dose of study medication and a per-protocol population who provided baseline and week eight body weight measurements, were at least 80% compliant and who did not take steroids between baseline and week eight
Differences between groups were studied by analysis of covariance
Differences from placebo at week four and week eight are presented as mean 95% CI
A P<0.05 was used to denote statistical significance.

Data Collection Summary:

Timing of Measurements

Patients were weighed on spring balance scales without shoes and wearing light clothing
Body composition was measured using a Bodystat 1500 bioelectrical impedance analyzer. All assessments were made with the patient supine and limbs apart.
Electrodes were placed over the wrist and ankle joints and metacarpal and metatarsal heads
Repeat measurements were performed using the same pair of limbs
Resistance was measured at 200Hz
Values for total body water were derived using equations validated in a similar patient group
Lean body mass was calculated assuming that lean tissue contains 73% water.

Dependent Variables

Change in body weight between baseline and week eight was the primary endpoint. Secondary end points were survival from random assignment and changes in lean body mass, quality of life variables, performance status and C-reactive protein between baseline and week eight.

Independent Variables

EPA Diethylester provided as soft gelatin capsules and manufactured by Scotia Pharmaceuticals. The diester was manufactured from fish oil derivatives and consisted of at least 95% propane diol diester compound formed with EPA at both ester linkages.

Control Variables

The placebo capsules contained medium-chain triglyceride which was also blended with the diester oil to allow blinding of the different doses to be achieved. The placebo was also manufactured by Scotia Pharmaceuticals.

Description of Actual Data Sample:

Initial N: 518 total (355 men, 163 women)
Attrition (final N): 270 (248 lost due to follow-up, death, adverse events or other reasons)
Age: Median age was 67 years (range 31 to 85 years)
Other relevant demographics: At baseline, 231 patients had lung cancer, 198 had upper GI cancer, 83 had lower GI cancer and six had unclassified GI cancer
Anthropometrics: Mean BMI of 21kg/m²
Location: United Kingdom.

Summary of Results:

Key Findings

Mean weight loss at baseline was 18% (N=518)
Over the eight-week treatment period, both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival, weight or other nutritional variables
A trend in favor or EPA with analysis of the primary endpoint at eight weeks showed a borderline non-significant treatment effect (P=0.066)
Relative to placebo, mean weight increased by 1.2kg with 2g EPA (95% CI: 0kg to 2.3kg) and by 0.3kg with 4g EPA (-0.9kg to 1.5kg).

Author Conclusion:

The results from this study indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia. Future studies are warranted and should concentrate on other agents or combination regimens.

Funding Source:

Industry:

Scotia Pharmaceuticals, United Kingdom

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

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?		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)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	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?		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?		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?		Yes
	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?	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?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	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)?	Yes
	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?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
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