H. San Juan de Alicante, Alicante, Spain

Background: Fatigue is one of the cancer-related symptoms that has the greatest impact on patients’ lives. This survey was designed to better understand the functional and psychological impact of fatigue and to determine, according to the patient’s perception, the load of fatigue relative to other symptoms.

Methods: A cross-sectional, self-administered survey was conductedfrom August-October 2007. Patients were 18 years old, with adiagnosis of cancer, and had received their last therapy session2–12 months ago. Demographic and tumor information werecollected. The survey included 6 questions about the emotionaland social impact of fatigue and the patient’s perceptionof the oncologist’s response to reports of fatigue. Fatigueimpact on emotional well-being was measured by a visual analoguescale (0–100). Questions about functional and social impactwere rated on a 5-point Likert scale. Descriptive statisticswere used to summarize demographic variables and responses.

Results: The survey was completed by 505 respondents (mean age 58.8 years; 55.2% women). Most tumors were located in the breast (26.5%), digestive system (20.8%), and lung (14.5%). Altogether 97.8% of patients experienced fatigue while receiving chemotherapy. Fatigue treatment was discussed with the oncologist in 72.9% of the cases while only 61.2% of patients reported receiving treatment for fatigue. Fatigue impact on emotional well-being was 54.9 (SD: 19.2). Over 65% of the patients felt that at least 50% of the time, fatigue prevented them from participating in social activities, in about 60% of patients, fatigue prevented their daily activities. Independent of sex or tumor type, fatigue was remembered as the most bothersome symptom of cancer.

Conclusions: Fatigue has substantial emotional and social impact on cancer patients and is perceived by patients as the symptom that causes greatest impairment to their daily activities.

Cancer Treatment Centers of America, Zion, IL

Background: Pain and fatigue are frequent, difficult to manage, and negatively impact quality of life (QOL) in pancreatic adenocarcinoma patients (PCpts) causing some to seek CAM therapy in place of or in conjunction with conventional analgesics. But the efficacy of CAM on pain and fatigue has not been adequately tested in controlled trials. We employed an alternative strategy by abstracting pain and fatigue scores from the EORTC-QLQ-C30 questionnaire administered to PCpts treated at Midwestern Regional Medical Center, an integrative oncology center offering conventional and CAM treatment.

Methods: 50 PCpts treated with chemotherapy and/or radiation clinically appropriate for advanced PC + CAM were evaluated. The CAM group (n=36) had 70%, 11%, and 19% and the nonCAM group (n=14) 71%, 14%, and 15% Stage IV, III, and II tumors respectively. PCpts received narcotic and anti-inflammatory agents consistent with ASCO and NCCN guidelines. CAM treatments included Green Tea Extract; Melatonin; and high-potency multivitamins. Baseline, 3 month(M), and 6M data were analyzed.

Results: Median baseline, 3M and 6M pain scores were: 50; 0; 33.3 and 75; 16.6; 83.3 for CAM and nonCAM respectively; not significant (NS) CAM vs nonCAM at any time point by non-parametric tests. Pain control at 3M was improved significantly vs baseline levels for each cohort; p=0.02 (CAM) and 0.03 (nonCAM) by paired 2 tail t tests. The relative numbers of PCpts with manageable pain ( 33) were comparable for CAM vs nonCAM at baseline (41% vs 36%) and 3 M (81% vs 90%), but not at 6M (67% vs 22% CAM vs nonCAM respectively, (p<0.05 by ?² test). Median baseline, 3M and 6M fatigue scores were: 55.5; 33.3; 33.3 and 44.4; 33.3; 66.6 for CAM and nonCAM respectively (NS, CAM vs nonCAM at any time point). By paired 2-tail t tests, 3M (p=0.01) and 6M (p=0.02) values were improved significantly vs baseline in CAM but not nonCAM cohorts.

Conclusion: This exploratory study shows that CAM treatment may improve fatigue and extend the period of effective pain control by conventional analgesics in PCpts. Given the negative impact exerted by pain and fatigue on QOL in this difficult to manage malignancy, CAM

H. Liu, J. A. Sloan, D. J. Sargent, D. V. Satele, P. L. Schaefer, M. Y. Halyard, A. Grothey, Y. I. Garces, P. D. Brown and J. C. Buckner

Mayo Clinic, Rochester, Rochester, MN; Toledo Clinic, Toledo, OH; Mayo Clinic, Scottsdale, AZ

Background: Fatigue is a prevalent and debilitating symptom reported by cancer patients (pts) which compromises a pt's quality of life (QOL). This study examined the relationship between PR fatigue and QOL as well as cancer-related symptoms (CRS) in 43 North Central Cancer Treatment Group and Mayo Clinic Cancer Center clinical trials.

Methods: 3,915 pts from 43 oncology clinical trials provided baseline fatigue data on a single-item 0–100 point scale. Pts' QOL assessment included a single-item overall QOL and associated QOL domains measured by numerical analogues, the Profile of Mood States (POMS), and PR symptom assessment measures. Associations between fatigue and QOL domains were assessed by Spearman correlation coefficients. Wilcoxon rank sum test compared QOL scores between pts with clinically deficient fatigue(CDF, score 50) vs. no clinically deficient fatigue (nCDF, score>50). Changes from baseline in fatigue and QOL were compared by Wilcoxon rank sum test with a 20-point change defined as clinically meaningful.

Results: 38% of ptsreported CDF at baseline and 45% of pts reported CDF at lastassessment. Fatigue was only moderately correlated at best withoverall QOL, pain, POMS, social and physical function (Spearmanrho's of .27,.40, .56, .38 and .38 respectively). Pts with CDFaveraged over 10 points lower overall QOL, pain, POMS, social,and physical function (see table below, all p<.0001) as wellas worsening CRS including sleepiness, nausea, headache, abnormalsweating, trouble sleeping, dry mouth, and sexual dysfunction(all p<.001). Pts with 20+ points worsening in fatigue declinedin overall QOL, physical function, pain and POMS (all p<.0001).

Conclusions: Patients with CDF suffer greater deficits in QOL and CRS. Patients report fatigue as distinctly different from overall QOL, pain, physical, social, mood status and CRS. Fatigue appears with a broad spectrum of CRS clusters. Routine measurement and management of fatigue could impact QOL and treatment-related symptoms.

M. D. Anderson Cancer Center, Houston, TX

Background: Fatigue is the most frequent symptom in advanced cancer. No standard treatment is available. We previously found that open-label donepezil significantly improved fatigue by day 3 and 7 in patients (pts) on opioids for cancer pain (Fisch et al, ASCO 2003). The purpose of this study was to compare donepezil (D) with placebo (P) for fatigue in pts with advanced cancer.

Methods: In this randomized, double-blind, placebo-controlled trial, pts with fatigue score = 4 on a 0 to 10 scale (10 = worst fatigue) for > 1 week, hemoglobin = 10g/dl for = 4 weeks, and no major contraindication to D were randomized to receive D 5 mg or P orally every morning for 7 days. All pts were offered open-label D during week 2. Assessment included: research nurse daily phone call for fatigue and toxicity evaluation, Edmonton Symptom Assessment System (ESAS), Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F), Sleeping Pattern Assessment, and overall effectiveness of the treatment. The FACIT-F fatigue subscale score on day 8 was considered the primary endpoint.

Results: 103 pts were evaluable for final analysis. Mean difference in scores for symptoms intensity between baseline and day 8 are shown in Table 1. FACIT-F fatigue subscale score at day 8 decreased a mean of 6 (10.6 SD) in the D arm (p < 0.001) and 7.2 (9.5 SD) in the P arm (p < 0.001). There was no significant difference in fatigue improvement between both arms according to the FACIT-F subscale (p = 0.57) and ESAS fatigue (p = 0.18) scores, and no significant difference in sleep quality score between D and P. On day 15 of the open-label phase, mean fatigue intensity remained significantly improved as compared to baseline on FACIT-F fatigue subscale (p < 0.001) and ESAS fatigue (p < 0.001) scores. No significant toxicities were observed.

Conclusions: Both donepezil and placebo resulted in significant fatigue improvement. Donepezil was not significantly superior to placebo after one week. Our pilot findings are probably due to placebo effect.

Cancer Treatment Centers of America, Zion, IL

Background: Fatigue is the most common and disabling symptoms experienced by cancer patients. No study has prospectively quantified the relationship between fatigue and patient satisfaction (PS) in advanced cancer. We therefore assessed this relationship before the start of chemotherapy and at 3 and 6 months after treatment at our integrative cancer treatment center.

Methods: 294 cancer patients treated at Cancer Treatment Centers of America between 04/01 and 11/04. Of 954 patients at baseline, only 294 were available for follow-up at 6 months. Fatigue was measured using the EORTC QLQ-C30 3-item fatigue subscale. Scores ranged from 0–100, higher scores indicating more fatigue. PS was measured using Ferrans & Powers Quality of Life Index (QLI). Scores ranged from 0–30, higher scores indicating better QoL. The mean fatigue scores were compared using ANOVA across the 3 time periods at baseline, 3 and 6 months. The relationship between fatigue and QLI was evaluated using multiple linear regression at all 3 time points.

Results: Of 294 patients, 106 were males and 188 females. 91 had breast ca, 52 colorectal, 43 lung, 25 pancreas, 13 prostate, and 70 had other cancers. 112 were newly diagnosed and 182 had received prior treatment elsewhere. The mean fatigue scores at baseline, 3 and 6 months were 43.6, 37.3, and 41.8 respectively; the scores at baseline and 3 months were significantly different (p = .009). At baseline, after controlling for age, gender, prior treatment history, and tumor stage at diagnosis, every 10 unit increase in fatigue was significantly associated with 1.3 units decrease in QLI health subscale. Similarly at 3 and 6 months after treatment, every 10 unit increase in fatigue was significantly associated with 1.2 and 1.4 units decrease in QLI health subscale.

Conclusions: In our study, we found that fatigue is a strong correlate of PS independent of the effects of age, gender, prior treatment history and tumor stage at diagnosis during the first 6 months of treatment. Interestingly, fatigue showed a significant improvement after 3 months of treatment and returned back to baseline levels at 6 months. This finding needs to be investigated further to evaluate the impact of integrative cancer care services on PS.

University of Arkansas for Medical Sciences, Little Rock, AR

Background: Over 60% of patients with multiple myeloma (MM) are anemic (Hb < 12 g/dL) at diagnosis. Nearly all become anemic during aggressive treatment for MM and many require red blood cell (RBC) transfusions. Anemia can contribute to fatigue, the most common and often the most distressing symptom for patients with cancer.

Methods: A randomized trial with repeated measures compared the effects on fatigue and performance of a home-based exercise program that combines aerobic and strength resistance training with a usual care/control condition. Measurements were the Profile of Mood States (POMS) fatigue scale, Functional Assessment of Cancer Therapy - Fatigue (FACT-F) and 6-minute walk test. Patients were newly diagnosed with MM and were enrolled in an aggressive treatment protocol that included tandem peripheral blood stem cell transplants. All patients in the study received epoetin alfa according to an algorithm that allowed increases in Hb up to 15 g/dL before dose reductions or delays. Planned enrollment is 160.

Results: The table below shows data from 82 patients with measurements at baseline just before induction chemotherapy and just before stem cell mobilization. Trends toward less fatigue and better performance are seen in the exercise group compared to the control group.

Conclusions: These preliminary findings suggest exercise therapy during aggressive treatment for MM benefits patients by decreasing their fatigue and improving their performance status.

The University of North Carolina, Chapel Hill, NC; Navitas Cancer Rehabilitation Centers, Westminster, CO

Background: Loss of lean mass during cancer treatment has been correlated with increases in fatigue (F) levels. Exercise is related to decreases treatment related fatigue and has been shown to thwart muscle loss.

Methods: Twenty female subjects, ages ranging from 35 to 70 years, were recruited for the 21 week study. A randomized two-group (exercise and control) design with multiple measurements [Pre-surgery (PS), Post-surgery (POS), 1^st assessment during Chemotherapy (Chemo1), 2^nd assessment (Chemo 2), 3^rd assessment (Chemo 3), and at the end of the experiment (FA)] was used. Percent of lean body mass (%LBM) and F levels were measured as dependent variables. Also, creatine kinase (CK) and total caloric intake (TCI) were measured to explain changes in %LBM and F. Data were analyzed using a two-way mixed model ANOVA with repeated-measures.

Results: No significant difference in %LBM from PS to FA (p = 0.82) was observed. However, a significant interaction effect between groups and %LBM from PS to FA was observed (p<0.000). Post hoc analyses revealed significant difference in %LBM between groups at the FA (p = 0.004). Significant differences in F scores were observed between PS and FA (p=0.008). Post hoc analyses revealed significant difference in F scores between groups at Chemo 1, (p=0.001), Chemo 2, (p=0.005), and FA (p=0.000). No differences in CK were noted, however significant differences were noted between groups at PS (p=0.000) and FA (p=0.000) for TCI.

Conclusions: The results suggest that initiating a regular individualized prescriptive exercise immediately following surgical recovery and continuing through at least 12 weeks during chemotherapy treatment positively impacts %LBM and deceases F when compared to patients not involved in any exercise.

G. R. Morrow, L. J. Gillies, J. T. Hickok, J. A. Roscoe, D. Padmanaban and J. J. Griggs

Univ of Rochester Cancer Ctenter, Rochester, NY

Background: Fatigue is the most common adverse effect reported by patients undergoing cancer treatment. Several large studies have shown up to 90% may experience fatigue sometime during treatment. Approximately a quarter report that their fatigue persists for months or even years beyond cancer treatment. Control of this debilitating side effect remains inadequate.

Methods: 51 Women (mean age=54.5 yrs) who completed breast cancer treatment an average of 23.5 months previously and who were reporting persistent fatigue were enrolled in a one month open label trial of modafinil (Provigil 200 mg with breakfast). Four patients did not complete the trial: 3 dropped out within a week complaining of ‘agitation’ (all were very slight with weights under 110#), 1 patient found she was unexpectedly pregnant and was withdrawn from the study. All patients completed psychometrically sound measures of fatigue and other side effects before and after treatment.

Results: The mean fatigue severity level at baseline for the 51 enrollees was 6.9 on a scale where 0 = ‘not present’ and 10 = ‘as bad as you can imagine’. After treatment, mean fatigue severity had fallen to 3.7 (p<.01). Forty-four of the 51 (86%) reported at least a one point improvement over the course of the one month study. Patient-reported global effectiveness measured after treatment supported the finding that modafinil was an effective treatment for fatigue; the mean rating was 5.0 (s.d.=2.0: with 1 = ’no benefit’ and 7 = ’great improvement’). Fifty one percent reported improvement in sleep and 51% reported less drowsiness. Additional improvements were reported by a majority of patients in general activity (64%), mood (63%), walking ability (63%), normal work ability (66%), relations with other people (66%) and enjoyment of life (61%).

Conclusions: Patients with fatigue that persisted an average of almost two years following cancer treatment experienced a benefit from modafinil in an open label trial. If these findings are confirmed by a randomized clinical trial currently underway, modafinil could provide clinical benefit for the unfortunately common side effect of cancer-related fatigue.

Clinical predictors of severe fatigue in solid tumor patients seeking acute care

R. Valdres, E. Manzullo and C. P. Escalante

U Texas M. D. Anderson Cancer Center, Houston, TX

Background: Fatigue is the most common symptom of cancer patients and has been described in various populations. Our objectives are to describe solid tumor patients (STP) and clinical factors associated with severe fatigue (defined as worst fatigue in past 24 hours 7/10) in an acute care setting and to determine whether certain clinical factors available during the emergency center (EC) visit identify patients with severe fatigue.

Methods: A retrospective cohort of 653 STP admitted to the EC from 5/1/01 to 8/15/01 was studied. Data abstracted from the medical record included demographic, clinical and cancer treatment factors. Descriptive statistics, chi-square and "student" t-tests were utilized. In developing a preliminary predictive model, stepwise logistic regression was employed.

Results: The mean age was 56 years (range, 19–92); 333 (51%) were female. The most frequent malignancies were breast cancer 119 (18%) and lung cancer 98 (15%). The majority, 345 (53%) had controlled disease. Of the cohort, 277 (58%) had Zubrod performance scores 2. Half (326) were not currently receiving cancer treatment. Fifty-seven percent (372) had severe fatigue and over half (51%) had both severe fatigue and severe pain. (Table 1)  

Conclusions: A majority of STP seeking acute care has severe fatigue. This preliminary model identifies clinical factors in STP with severe fatigue in our EC. Model validation is necessary. If validated, some patients may benefit from earlier identification and referral for fatigue management strategies. This may improve their overall quality of life and potentially influence a lower care level with less cost.

Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatigue syndrome.

Bounous G, Molson J.

Department of Surgery, McGill University, and Medical Research Council of Canada.

The chronic fatigue syndrome (CFS) is typically associated or follows a recognized or presumed infection. Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen. As an antioxidant, glutathione (GSH) is essential for allowing the lymphocyte to express its full potential without being hampered by oxiradical accumulation. Hence, protracted challenge of the immunocytes may lead to cellular GSH depletion.

Because GSH is also essential to aerobic muscular contraction, an undesirable competition for GSH precursors between the immune and muscular systems may develop. It is conceivable that the priority of the immune system for the survival of the host has drawn to this vital area the ever-diminishing GSH precursors, thus depriving the skeletal muscle of adequate GSH precursors to sustain a normal aerobic metabolism resulting in fatigue and eventually myalgia.