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)

Small-cell lung cancer (SCLC) is highly chemosensitive but up to 70% of patients with limited disease and more than 90% of patients with extensive disease will relapse after first-line treatment. There are several standard chemotherapy regimens used for second-line treatment yet the prognosis for patients requiring this treatment remains poor. The topoisomerase-I inhibitor, topotecan, has achieved response rates of up to 22% in previously treated patients with SCLC and survival almost double that achieved with other single agents. Compared with cyclophosphamide/doxorubicin/vincristine (CAV), single-agent topotecan achieved a higher response rate, longer survival and statistically significant improvements in dyspnea, hoarseness, fatigue, anorexia and interference with daily activities. Brain metastases are common in SCLC. Topotecan crosses the blood-brain barrier and shows promise for the management of brain metastases.
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PMID:The role of topotecan in treating small cell lung cancer: second-line treatment. 1456 8

The aim of this study was to determine the antitumour activity and toxicity of thalidomide in patients with metastatic melanoma. Between July 1999 and July 2001, 20 patients with metastatic melanoma were enrolled into this study. Patients were required to have progressive disease following standard therapies (unless there was a known contraindication for their usage) and to be free from symptomatic brain metastases. Thalidomide was administered orally at a starting dose of 200 mg/day, with increments of 100 mg every 7 days to a maximum dose of 800 mg/day. Patients experiencing intolerable side effects had their dose reduced to the maximum tolerated dose. Response and tolerance to treatment were assessed at 4 week intervals and therapy was continued until progression of disease or development of intolerable side effects despite appropriate dose reduction. All 20 patients were assessable for response. No objective response (complete or partial remission) was observed. In seven patients (35%), stable disease with a duration of 12-32 weeks (median 16 weeks) was seen. The median time to progression for all patients was 8 weeks (range 5-32 weeks) and the median overall survival was 20 weeks (range 7-130+ weeks). Treatment was generally well tolerated. Nine patients (45%) were able to tolerate the maximal planned dose of thalidomide (800 mg/day). Constipation, fatigue, somnolence and dryness of skin or mouth were the most common side effects. Thalidomide appears to possess cytostatic activity in patients with metastatic melanoma. Further studies of thalidomide in melanoma are warranted.
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PMID:Phase II study of thalidomide in patients with metastatic melanoma. 1509 Nov 95

To prospectively assess patient-rated symptoms in patients with brain metastases treated with whole brain radiotherapy, these patients were asked to rate their symptoms on the Edmonton Symptom Assessment Scale (ESAS) before, and 1, 2, 4, 8, and 12 weeks following the radiation treatment. ESAS evaluates pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, sense of well-being, and shortness of breath on a scale of 0-10 (0=absence of symptom and 10=worst possible symptom). Patients with a language barrier or significant cognitive impairment were excluded. The mean difference of ESAS symptoms at each follow up were compared with baseline and P < 0.01 was considered statistically significant. One hundred seventy patients (102 female and 68 male) were included between January 1999 and January 2002. Their median age was 66 years (range 33-84) and the median Karnofsky performance score (KPS) at baseline was 60 (range 20-90). The most common primary cancer sites were lung (99; 58%), breast (32; 19%), gastrointestinal (16; 9%), unknown (14; 8%) and others (9; 6%). One-third had significant weight loss (> or =10% over the last 6 months). All patients were prescribed dexamethasone at varying doses during radiotherapy. The dose fractionations were 20 Gy in 5 fractions, 138 (81%); 30 Gy in 10 fractions, 7 (4%); and others, 25 (15%). The baseline mean +/- SD for ESAS scores were: pain 2.4 +/- 2.8, fatigue 5.3 +/- 2.8, nausea 1.3 +/- 2.2, depression 2.8 +/- 2.7, anxiety 3.6 +/- 3.0, drowsiness 3.5 +/- 2.9, appetite 3.0 +/- 3.2, sense of well-being 3.8 +/- 2.7, and shortness of breath 2.3 +/- 2.5. For the entire cohort, after the delivery of palliative radiotherapy for brain metastases, there were statistically significant deteriorations in the mean differences from the baseline for the following ESAS domains: fatigue 1.0 to 1.8; drowsiness 1.2 to 1.8; and appetite 2.2 to 2.4. The data demonstrate that certain parameters of quality of life worsen after whole brain radiotherapy.
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PMID:Prospective assessment of patient-rated symptoms following whole brain radiotherapy for brain metastases. 1604 3

The aim of this study was to determine the antitumor activity of 17-(Allylamino)-17-demethoxyge-ldanamycin (17-AAG), a heat shock protein 90(hsp90) inhibitor in patients with metastatic papillary renal cell carcinoma (RCC) or metastatic clear cell RCC. Eligible patients were divided into 2 cohorts based on histological subtype: papillary or clear cell RCC. All patients had advanced RCC with measurable disease, a Karnofsky performance status of at least 70, and no evidence of brain metastases. Twelve patients with clear cell RCC and 8 patients with papillary RCC were treated with 17-AAG on this phase II trial. 17-AAG was given intravenously at 220 mg/m(2) twice weekly for 2 weeks followed by a week of rest. Cycle length was 21 days. No patient in either cohort achieved a complete or partial response. Toxicities included elevated liver function tests, optic neuritis, dyspnea, fatigue, and gastrointestinal side effects. Six of the 20 patients required dose reduction. At the dose and schedule used in this trial, 17-AAG did not achieve objective response in the treatment of clear cell or papillary renal cell carcinoma patients.
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PMID:A phase II trial of 17-(Allylamino)-17-demethoxygeldanamycin in patients with papillary and clear cell renal cell carcinoma. 1683 3

Three patients with advanced renal-cell cancer were treated with sunitinib 50 mg daily for 4 weeks followed by a rest period of 2 weeks because of progressive disease. The first patient developed stomatitis and a painful blister on his foot. Complaints disappeared after temporary discontinuation of treatment. Re-treatment at a lower dosage was successful until disease progression. The second patient developed skin discolouration, fatigue, fever and diarrhoea. After treatment was interrupted shortly, these symptoms disappeared and sunitinib was recommenced at a lower dosage. The patient went on to develop stomatitis, thrombocytopenia and hypertension (treated with amlodipine). She subsequently had hand-foot syndrome. She died due to brain metastases. In the third patient symptoms of disease returned during the rest period, because of which he received a reduced dosage of sunitinib on a continuous base. He developed diarrhoea which disappeared after a short interruption of the drug. Sunitinib has been approved for the treatment of advanced renal-cell cancer and imatinib-resistant gastro-intestinal stromal tumours. This novel targeting molecule is a tyrosine-kinase inhibitor of vascular endothelial growth-factor receptors, platelet-derived growth-factor receptors and c-Kit. It can induce adverse events that differ from those observed in treatment with conventional cytotoxic agents. The adverse effects are reduced by lowering the dosage and in the rest period within the treatment cycle.
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PMID:[Adverse effects of the tyrosine-kinase inhibitor sunitinib, a new drug for the treatment of advanced renal-cell cancer]. 1755 72

We conducted a single institution phase II trial to evaluate the tolerability and effectiveness of therapy with arsenic trioxide (ATO) and ascorbic acid (AA) with temozolomide (TMZ) in patients with advanced melanoma. Planned enrollment was for 40 patients. Eligible patients were required to have metastatic melanoma with or without brain metastases, an ECOG performance status of 0-2, and adequate organ function. The primary endpoints were overall response rate and degree of grade 4 toxicity. ATO was administered as a loading dose at 0.25 mg/kg/day for 5 days during week 0, and then twice weekly at 0.35 mg/kg during an 8-week cycle. Each infusion of ATO was followed by an infusion of 1000 mg of AA. TMZ was given at the standard dose of 200 mg/m for 5 days during weeks 1 and 5 of each cycle. Eleven patients were enrolled with 10 evaluable for response, five with central nervous system disease. No responses were seen among the first 10 patients and on the basis of a predetermined stopping rule, the trial was terminated. Common grade 1 and 2 side effects included nausea and vomiting (10), fatigue (six), edema (six), rash (six), and elevated AST or ALT (six). Grade 3 and 4 side effects included nausea and vomiting (three), elevated AST or ALT (two), seizure (one), and renal failure (one). This is the first trial combining ATO with chemotherapy in a solid tumor. ATO and AA were administered in the outpatient setting with TMZ in 11 patients with an acceptable side effect profile. No responses were seen in the first 10 evaluable patients leading to early closure of the study. Further studies using ATO and AA with TMZ with this dosing schedule in advanced melanoma are not warranted.
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PMID:Phase II trial of arsenic trioxide and ascorbic acid with temozolomide in patients with metastatic melanoma with or without central nervous system metastases. 1833 52

Fatigue is a common advanced cancer symptom. Clinical features are not well known. The authors surveyed consecutive patients admitted to a palliative medicine program to identify clinical correlates of fatigue. Data collected included age, sex, performance status, primary site, prior chemotherapy/radiation therapy, and blood transfusions. Visual analogue scales assessed fatigue, quality of life, and ability to perform daily activities. Weight change was estimated. Laboratory results including lactate dehydrogenase and hemoglobin were recorded. Fatigue severity was associated with brain metastases, poor performance status, poor quality of life, and reduced ability to perform activities. Prior radiation therapy was associated with less severe fatigue. Age, sex, and hemoglobin level were not associated with fatigue. Fatigue was universal on referral. Brain metastases and poor quality of life independently predicted severity. Hemoglobin level did not predict fatigue. Further studies are necessary to define the clinical features and relationships of fatigue.
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PMID:Fatigue in advanced cancer: a prospective study. 1853 63

Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand-foot syndrome and a combination of grade 1-2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity.
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PMID:Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer. 1975 85

Symptom occurrence has been shown to predict treatment course and survival in cancer patients. The M. D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) was recently validated as a tool for primary brain tumor patient self-report of symptoms. This study evaluated the reliability and validity of the MDASI-BT in patients with brain metastases. Data collection included demographic and clinical factors, and the MDASI-BT (0-10 scale). Construct validity was assessed using confirmatory factor analysis, and known-group validity was evaluated by detecting group differences due to disease severity and treatment approach. For reliability, Cronbach's alpha values were computed for each subscale. A sample of 124 patients participated, of which 53.2% were women. Participants were primarily white (79.8%) and married (78.2%), and a variety of solid tumor malignancies were represented. Factor analysis revealed six underlying constructs, including affective symptoms, cognitive dysfunction, focal neurologic deficits, constitutional and gastrointestinal symptoms, and interference with life. The solution with these factors explained 68.4% of the variance. Mean symptom scores were 1.2 and 2.6, and mean interference scores were 1.8 and 4.3 for patients with good and poor Karnofsky scores, respectively (P<0.001). These subscales were also sensitive to opioid analgesic use, with group differences of 1.5 and 2.2 (P<0.001). Cronbach's alpha was 0.9 for each of the two subscales. Fatigue, sleep disturbance, drowsiness, distress, and dry mouth were the most severe symptoms. The MDASI-BT demonstrated validity and reliability in brain metastases patients and can be used to identify and monitor symptom occurrence in relation to treatment course and survival.
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PMID:Clinical utility of the MDASI-BT in patients with brain metastases. 1867 20

The case was a 64-year-old man. He was diagnosed as gastric cancer, lymph node metastases, brain metastases, bone marrow carcinomas, and disseminated intravascular coagulation(DIC). He was started on methotrexate(MTX)/5- fluorouracil(5-FU)sequential therapy(weekly administration of MTX(100 mg/m(2), iv bolus)followed by 5-FU(600 mg/m(2), iv bolus)with a 3 h interval). DIC was resolved, and the tumor marker decreased remarkably. Four weeks later, he received zoledronic acid 4 mg to prevent skeletal complication. Next day, fatigue and anorexia onset. Six days later, laboratory data showed severe hypocalcemia. He was started on calcium gluconate 3.4 g/day. The calcium level was normalized in twelve days, and the symptoms were improved. MTX /5-FU therapy was resumed, and his condition remained stable. However, after the ninth dosage, he developed fatigue and low back pain, and the DIC relapsed. We started paclitaxel therapy. But it was not effective and he died ten days later. It was considered that careful attention to hypocalcemia is necessary when we use zoledronic acid for the bone marrow carcinomas treated with chemotherapy.
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PMID:[A case of bone marrow carcinosis from gastric cancer that presented hypocalcemia caused by zoledronic acid during the treatment of methotrexate/5-fluorouracil sequential therapy]. 1929 78


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