- Click here for explanation of classification scheme.

The specific aim was to:

• Examine the relationships among physiologic, psychological, and nutritional variables hypothesized by Winningham (1992) to be associated with fatigue in two groups of patients with melanoma receiving biotherapy or biochemotherapy:
  • Those currently receiving treatment (on-treatment group)
  • Those who had completed treatment 6-12 months prior (off-treatment group)

 

• Men and women older than 18 years of age
• Diagnosed with melanoma
• For the on-treatment group:
  • Currently receiving biochemotherapy
  • Completed at least 2 cycles of treatment
• For the off-treatment group:
  • Completed a course of biochemotherapy 6-12 months prior to data collection

Not discussed

Recruitment --Not discussed

 

Design--Cross-sectional, descriptive design 

 

Blinding used (if applicable)--N/A

Intervention (if applicable)

No specific measurement methodology has been developed for testing Winningham's theory, nor have instruments been developed specifically for that purpose. The researchers attempted to bring together the shortest, least tiring instruments (with adequate psychometric properties) with the goal of reducing respondent burden.

Patients in both groups completed a series of questionnaires and diet recall.

Questionnaires selected to explore the variables of interest for this specific study included:

• Fatigue--Schwartz Cancer Fatigue Scale (SCFS), a six-item instrument that measures cancer-related fatigue in physical and perceptual dimensions. The scale is able to discriminate between patients on-treatment and those who had completed treatment. Test-retest reliability was established for internal consistency.
• Activity--Leisure Time Exercise Questionnaire (Godin and Shepard, 1985), a two-item instrument to assess exercise behavior. Test-retest reliabilty was established for internal consistency.
• Physical function--Karanofsky Performance Status Scale (Karnofsky, Abelmann, Craver, Burchenal, 1948), a 11-level tool (ranging from 100-0; normal to dead) for quantifying the physical functioning of patients with cancer. Often considered the "gold standard" by many investigators. Poor functioning is associated with increased diseased severity and survival time
• Cancer and cancer-treatment related symptoms--Adapted Symptoms Distress Scale (ASDS) Form 2 (Rhodes, McDaniel, Horman, Johnson, Madsen, 2000), a 31-item instrument which measured the relationship between fatigue and other reported symptoms of biotherapy. Participants were asked to rate each item in terms that best described how they felt the previous week. Two subscales, symptom occurrence and symptom distress, were derived from the scale.
• Anxiety and depression--Hospital Anxiety and Depression Scales (HADS) (Zigmond, Snaith, 1983), a 14-item questionnaire developed to assess anxiety and depression for use in nonpsychiatric hospital settings. Two subscales were produced, one for depression and one for anxiety. A cut-off score of 8 indicates a need for further investigation for anxiety or depression, and a score of 11 or more indicates clinical anxiety or depression.  
• Quality of life (QOL)--Graham and Longman's QOL Scale (1987), a two-question scale. Patients are asked to rate their QOL on a scale from 1 (poor) to 10 (excellent) and their degree of satisfaction with their current QOL from 1 (not at all satisfied) to 10 (very satisfied). The scale has been tested with cancer patients with inter-item correlation of 0.81 (p < 0.05).
• Nutritional intake and status--one, 24-hour dietary recall for the 24 hours prior to data collection. 

Statistical Analysis

• Spearman's Rho test to test relationships between fatigue and other variables (nutrient intake, anxiety, depression, distress symptoms, physical function status, and activity levels)
• Mann-Whitney U test used to test differences between the 2 groups of patients---on-treatment and off-treatment
• Results are presented as means ± SD
• p < 0.05 established as statistically significant

 

Timing of Measurements

At baseline, questionnaires administered during one routine visit to the medical oncology outpatient clinic

At the same time, height and weight were measured (method not presented)

Blood samples were collected for testing of of hemoglobin and serum magnesum (results not presented)

Nutritional intake:

At baseline, one 24 hour recall was collected from each patient. The 24-hour recall was entered into the Diet Analysis software program (Whitney, Cataldo, Rolfes, 2002).

Post-hoc

Data were collected on medications participants were taking to evaluate the impact of medications on fatigue.

Dependent Variables

• Fatigue
• Anxiety
• Depression
• Distressing symptoms
• Nutritional intake
• Weight

Independent Variables

Two groups of patients receiving biotheraphy or biochemotherapy:

•  On treatment group: currently receiving receiving treatment
• Off-treatment group: those who had completed treatment 6-12 months prior

Control Variables

Not discussed

 

Initial N: not discussed; only final sample N presented

Attrition (final N): 25 (17 males-68%, 8 females-32%)

on-treatment group--13 males, 6 females

off-treatment group--4 males, 2 females

Age: mean age: 47.5 y ± 8.3 y; range 30-64 y

Ethnicity: Caucasian

Other relevant demographics: No significant differences in demographic or disease variables between those on-treatment and those who had completed treatment

Anthropometrics: overall, sample was overweight or obese; mean weight of sample was 90.2 kg ± 29.5 kg (range 49.5-132.9 kg); mean BMI was 29.6 ± 5.69 (range 17.7-42.04). No significant differences between those on-treatment and those off-treatment.

Location: Oncology outpatient clinic in Missouri

 

Variable	On-treatment group Mean ± SD	Off-treatment group Mean ± SD	P-value
Fatigue score	17.16 ± 5.29	7.73 ± 0.58	0.000
Physical function score	82.5 ± 11.83	94.2 ± 10.2	NS
Anxiety score	15.1 ± 3.88	10.5 ± 1.52	0.01
Depression score	15.95 ± 2.97	9.5 ± 2.07	0.000
Symptom occurence score	17.68 ± 7.1	8.0 ± 3.35	0.004
Symptom distress score	17.37 ± 6.98	6.33 ± 4.42	0.001
Symptom experience score	35.05 ± 13.42	14.33 ± 3.04	0.002

• As assessed by the 24-hour recall, the on-treatment group consumed an average of 1939 ± 886 calories and the off-treatment group consumed an average of 2164 ± 933 calories. However, no significant relationship was established between fatigue and intake of specific nutrients or total caloric intake.
• Activity levels were found to be significantly lower in the on-treatment group than in the off-treatment group. Findings suggest that a considerable reduction in activity occurs during therapy; resumed 6-12 months later.
• Overall, psychological symptoms measured by anxiety and depression indicated a high prevalence of distress in all participants. 10 participants (40%) scored 8 or more for anxiety, and 15 (60%) scored 8 or more for depression. A significant difference was found between groups in scores for anxiety and depression, with the on-treatment group experiencing higher levels of psychological distress than the off-treatment group.
• Significant relationships were found between fatigue and depression (r = 0.649; p = 0.000), and fatigue and anxiety (r = 0.44, p = 0.026)
• Significant inverse relationships were found between total fatigue score and QOL (r = -.596, p = 0.002), and total fatigue scores and satisfaction with QOL (r = -0.632, p = 0.001). The off-treatment group had significantly higher ratings of QOL (p = 0.001), and satisfaction with QOL (p = 0.001).

Other Findings

Post-hoc analysis of medications found that;

• Most participants were taking at least one medication; range 0 to 7.
• Sedatives or opiates were taken by 5/25 patients (20%)
• Antidepressants were taken by 5/25 patients (20%); one patient was taking antidepressants to quit smoking and one for depression (however, not one of the patients scoring 11 or higher on the HADS.
• No difference in fatigue scores was found between those taking or not taking antidepressants, sedatives, or opiates.
• The number of medications taken was significantly correlated with the total fatigue score (r = 0.49, p = 0.012).

This study showed moderate overall fatigue in a sample of patients with melanoma who were receiving or who had received biochemotherapy. Fatigue was higher in the on-treatment group than for those in the off-treatment group. Activity level decreased in the on-treatment group but probably returns to pretreatment levels after 6-12 months.

Nutritional status and nutrient intake were not correlated to fatigue in this sample. The sample was predominantly overweight and obese with relatively high calorie intakes. The researchers postulated that when a patient population is consuming sufficient (or more than sufficient) calories, the relationship between dietary intake and fatigue is difficult to establish.

Psychological symptoms measured by anxiety and depression in this study indicated a high prevalence of distress. Depression as an adverse effect of biotherapy has been noted before in the medical literature. Given the strong relationship between depression and fatigue, depression must be given more attention, particularly in patients receiving biotherapy.

Winningham's model demonstrates its usefulness in helping to understand the phenomenon of cancer-related fatigue. The theory is the most sophisticated of the current theories proposed in the literature, but some serious issues of measurement need to be addressed. No specific measurement methodology or instruments have been developed for testing Winningham's theory. This study attempted to bring several measures together that reflected various aspects of the theory, but the respondent burden is great. The need for better measures of fatigue should be the focus of future research.

 

Industry:	Ortho Biotech Products Pharmaceutical/Dietary Supplement Company:
Not-for-profit	0 Foundation associated with industry:

Limitations of study:

• Methodology limitations and respondent burden
• Only one, 24 hour recall obtained from participants
• Small sample size. ? dropouts, only final sample size was presented. 
• ?generalizability; sample was predominantly overweight and obese, Caucasian 
• study funded by grant from Schering-Plough and Chiron Corporation which manufacturer interferon and interleukin