Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For cancer patients, fatigue is a disturbing symptom caused by many factors. Since fatigue is the most common side effect of localized radiation to the breast, this treatment provides a unique opportunity to follow patients prospectively as they develop one type of fatigue. We evaluated the effect of radiation treatment in 15 women with Stage I or II node-negative breast cancer who were otherwise healthy. Fatigue, contrary to our hypothesis, did not increase linearly with cumulative radiation dose over time. It dropped from the first to second week and rose in the third week. The cumulative effects reached a plateau in the fourth week (after an average of 17 fractions), which was maintained during the remaining weeks of treatment. Within 3 wk after treatment, fatigue had diminished. No patient had sustained depressive symptoms. Cardiopulmonary exercise capacity in 5 patients at 6 and 12 wk did not change from just before radiation. Other markers, including reverse triiodothyronine and pulse change with orthostatic stress, did not correlate with subjective fatigue nor cumulative radiation in 15 patients. The curve of the fatigue syndrome during treatment conforms to the adaptation of the organism to a continuing stress and begins to describe a mild fatigue syndrome associated with radiation.
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PMID:Fatigue syndrome due to localized radiation. 153 80

The application of recombinant DNA technology to the production of tumor necrosis factor has resulted in the availability of large quantities of a highly purified protein product. This product has been evaluated extensively in preclinical studies, which have documented a direct cytostatic and cytotoxic effect on human tumor cells, as well as a variety of immunomodulatory effects on various immune effector cells, including neutrophils, macrophages, and T cells. In addition, a number of anti-infective and metabolic effects have been documented. In addition to its in vitro effects, rTNF has been shown to have antitumor activity in vivo in preclinical studies involving both transplantable murine tumors and human tumor xenografts. Such observations have led to the evaluation of rTNF as a potential antineoplastic agent in humans. Both single- and multiple-dose phase I studies have confirmed that rTNF can be safely administered to patients with advanced malignancies in a dose range associated with anticancer effect without concomitant serious toxicities such as shock and cachexia. The most commonly observed clinical toxicities include constitutional symptoms, such as fever, chills, headache, and fatigue, and toxicities, which can be at least partially controlled with concomitant administration of nonsteroidal anti-inflammatory drugs, such as acetaminophen and meperidine. Hypotension, which occurs at high doses administered by short intravenous infusion, can usually be prevented by prehydration with intravenous fluids or otherwise controlled by the administration. An intense local inflammatory reaction at the injection site as well as thrombocytopenia appear to be the dose-limiting toxicities after subcutaneous and intramuscular administration. Neurologic toxicity is infrequent, except following continuous intravenous infusion, where it may manifest as transient focal neurologic deficits or seizure. Prolonged administration of rTNF at higher doses may be associated with transient, subclinical decreases in diffusing capacity. Patients with underlying cardiopulmonary disease should be excluded from rTNF therapy in future clinical studies until the end-organ toxicities of this agent are better defined. For at least one preparation of rTNF there appears to be no evidence for the formation of antibodies to rTNF in patients who receive multiple administrations of the agent. Pharmacokinetic studies have shown a relatively rapid clearance following intravenous infusion with a half-life of 15 to 30 min and dose-dependent pharmacokinetics. rTNF can be detected in the serum following intramuscular or subcutaneous injection at only relatively high doses, suggesting a decreased bioavailability with the routes of administration. Early phase I studies defined tolerable dose ranges for each route of administration and began to explore immunomodulatory and metabolic effects of rTNF.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recombinant human TNF-alpha: preclinical studies and results from early clinical trials. 155 Aug 75

We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U.
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PMID:A phase I trial of fluorouracil, leucovorin, and recombinant interferon alpha-2b in patients with advanced malignancy. 155 45

The quality of survival of 48 patients treated surgically for head and neck cancer was assessed using a problem-orientated self-administered questionnaire. The questionnaire was based on the European Organization for Research into the Treatment of Cancer (EORTC) core questionnaire to which a specific head and neck module was added. The following domains were studied: pain, fatigue, physical symptoms (gastrointestinal and 'other'), functional activity, psychological symptoms, overall physical condition and overall quality of life. For the analysis, five groups of patients were considered: laryngectomy (n = 15), pharyngolaryngoesophagectomy (n = 5), craniofacial procedure (n = 11), 'other operations' (n = 9) and patients with disease recurrence (n = 8). Each group identified different problem areas. Laryngectomees and 'other operation' patients reported relatively few problems, whereas patients with disease recurrence described difficulties in all of the domains examined. Symptoms of fatigue were common. Information collected in this way may facilitate improved rehabilitation and thus better quality of survival.
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PMID:Quality of life of patients treated surgically for head and neck cancer. 156 81

The optimal schedule for recombinant interleukin-2 (rIL-2) administration is unclear. Because the clinical and immunological effects of prolonged continuous exposure to rIL-2 are unknown, we have conducted a phase I study to assess the toxicity and feasibility of continuous low dose infusion of rIL-2 (EuroCetus) using central venous access with a portable infusion device on an out-patient basis. Twenty-two patients entered the study, 13 with melanoma and nine with renal cell cancer, age range 26-66 years (median 51), performance status less than or equal to 1. They were treated with one of the following doses per m2 per 24 h: 0.18 x 10(6) IU, 0.6 x 10(6) IU, 1.8 x 10(6) IU, 3 x 10(6) IU, 6 x 10(6) IU and 9 x 10(6) IU. Toxicity was evaluable in 20 patients receiving greater than or equal to 3 weeks treatment duration or in whom treatment was discontinued prematurely because of toxicity. Constitutional symptoms consisting of fatigue, malaise and fever up to 40 degrees C without significant organ dysfunction occurred with doses greater than or equal to 1.8 x 10(6) IU m-2. The maximum tolerated dose was 6 x 10(6) IU m-2 24 h-1. In all patients toxicity reached a peak at 3 weeks and resolved thereafter despite continued rIL-2 treatment. Peripheral blood eosinophilia (up to 66% of white blood cell count) followed the same pattern. An infection of the central venous access occurred in 55% of the patients but this was mostly asymptomatic. Thirteen patients were treated greater than or equal to 6 weeks and were evaluable for tumour response. A partial remission occurred in a patient with melanoma with a dose of 1.8 x 10(6) IU rIL-2 m-2 24 h-1.
Br J Cancer 1992 May
PMID:A phase I study of prolonged continuous infusion of low dose recombinant interleukin-2 in melanoma and renal cell cancer. Part I: Clinical aspects. 158 2

Fatigue is a common adverse effect of cancer and its therapy. However, the specific mechanisms underlying cancer fatigue are unclear. One physiologic mechanism may involve changes in skeletal muscle protein stores or metabolite concentration. A reduction in skeletal muscle protein stores may result from endogenous tumor necrosis factor (TNF) or from TNF administered as antineoplastic therapy. This muscle wasting would require patients to exert an unusually high amount of effort to generate adequate contractile force during exercise performance or during extended periods of sitting or standing. This additional effort could result in the onset of fatigue. Additionally, cancer fatigue may develop or become exacerbated during exercise as a consequence of changes in the concentration of skeletal muscle metabolites. These biochemical alterations may interfere with force that is produced by the muscle contractile proteins. These physiologic changes may play a role in the decision to include exercise in the rehabilitation plans of patients with cancer. They also may affect ideas about fatigue.
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PMID:Fatigue mechanisms in patients with cancer: effects of tumor necrosis factor and exercise on skeletal muscle. 159 64

We conducted a phase I study of low-dose cyclophosphamide and recombinant interleukin-2 (rIL-2) in 66 patients with advanced cancer resistant to standard therapy. All patients were evaluable for toxicity and 46 patients were evaluable for antitumor response. Patients evaluable for antitumor response included 23 with malignant melanoma, 10 with renal cell carcinoma, 4 with colon cancer, and 9 with various other solid tumors. All patients received i.v. cyclophosphamide (350 mg/m2) on day 1 followed by rIL-2 via 15 min i.v. infusion on days 4-8 and 11-15. The doses of rIL-2 ranged from 6.0 to 36.0 x 10(6) IU/m2. Each treatment cycle consisted of 21 days and a total of 113 cycles was administered. The number of treatment cycles administered per patient ranged from 1 to 8. The dose-limiting toxicities associated with rIL-2 included altered mental status, arthralgias, diarrhea, fatigue, fever, hypotension, nausea/vomiting, and peripheral edema. Twelve patients (18%) were removed from the study secondary to toxicity. Among the evaluable patients, 2 (4%) (malignant melanoma, renal cell carcinoma) developed a partial remission, 13 (29%) maintained stable disease, and 31 (67%) developed progressive disease. We conclude that the combination of low-dose cyclophosphamide and rIL-2 is tolerable in most patients but our data do not suggest an improved response rate for the combination vs. rIL-2 alone.
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PMID:Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer. 159 14

Stress, anxiety, and depression in patients who are undergoing treatment of cancer significantly compromise the quality of their lives. The impact of stress reduction by relaxation training and imagery was studied in 82 out-patients who were undergoing curative (73 patients) or palliative (9 patients) radiotherapy. Fifty-two females and 30 males were assigned randomly to a relaxation training condition (34 patients) as an adjunct to radiation or a control condition (29 patients), which entailed education and counseling along with the RT. Using pre- and posttests of the Profile of Mood States, significant (p less than .01) reductions were noted in the treatment group in tension, depression, anger, and fatigue. The results suggest that relaxation training substantially improves several psychological parameters associated with quality of life in ambulatory patients who are undergoing radiation therapy.
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PMID:Relaxation therapy as an adjunct in radiation oncology. 160 30

Mood states of cancer patients were assessed pre- and post-41.8 degrees C whole-body hyperthermia using the Profile of Mood States questionnaire. Results demonstrated a statistically significant increase in fatigue associated with decreased vigour which returned to baseline values by 72 h. In contrast, a significant improvement in depression was evident through 72 h following treatment. The relationship of this result to earlier studies of WBH-induced beta-endorphin is discussed.
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PMID:Changes in mood state following whole-body hyperthermia. 160 35

The combination of folinic acid (FA) and 5-fluorouracil (5FU) is the most active systemic chemotherapy against advanced colorectal cancer. Experimental and clinical studies have suggested that the activity of 5FU can be improved by the addition of alpha-interferon (IFN). To evaluate the possibility of a double modulation of 5FU, a pilot study was conducted in the period July 1989-December 1989 with the following regimen: FA (200 mg/m2 i.v. bolus x 5 days) + 5FU (400 mg/m2 i.v. in 15 min x 5 days) + alpha-2b IFN (10 x 10(6) IU subcutaneously on alternate days). FA and 5FU administrations were repeated every 28 days; IFN was administered every week. In the 16 treated patients, 4 partial responses, 4 no changes, and 8 with progression of disease were observed, with an objective response rate of 25% (95% CI, 7.8%-55.1%). Median duration of response was 9.5 months, as was overall survival. Toxicity (fever, fatigue, neurotoxicity, stomatitis and diarrhea) was considerable and led to a reduction in IFN doses in 10/16 patients. Due to the unfavorable cost/benefit ratio, the study was closed and a new trial, with different doses and schedule of IFN, was started within the GISCAD (Italian Group for the Study of Digestive Tract Cancer).
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PMID:High dose alpha-2b interferon + folinic acid in the modulation of 5-fluorouracil. A phase II study in advanced colorectal cancer with evidence of an unfavourable cost/benefit ratio. 160 56


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