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)

The current standard of care for soft tissue sarcoma (STS) is limb salvage surgery and adjuvant radiotherapy, with long-term survival rates of approximately 70%. However, the extensive surgical resection and subsequent reconstruction result in 50% of survivors living with chronic disability. Rehabilitation aims to optimize functional independence and quality of life, and is routinely offered to patients undergoing surgical treatment for STS. Unfortunately, there is a dearth of research related to rehabilitation in this area. We propose a model for assessing disability, for designing treatment interventions and for evaluating rehabilitative outcomes in STS. The World Health Organization's (WHO) international classification of functioning, disability, and health (ICF) is divided into three domains: 1) impairments (related to body structure and function), 2) activity limitations (related to usual self-care activities/activities of daily living), and 3) participation restrictions (related to social roles). A literature review of STS rehabilitation reveals that most studies have focused on disability assessment, with few papers describing or evaluating rehabilitation interventions commonly employed in STS. Clinicians are forced to extrapolate findings from other patient populations in order to evaluate the effectiveness of specific rehabilitation strategies (ie, those used for particular sequelae of STS, such as lymphedema or impaired exercise tolerance). There is strongest support for complex decongestive physiotherapy (targeting lymphedema) and aerobic exercise interventions (aimed at alleviating cancer-related fatigue and psychosocial sequelae). The most poorly researched topic is rehabilitation for genitourinary disability (both incontinence and sexual dysfunction). Most studies related to oncologic rehabilitation are restricted to the impairment level (eg, affecting range of motion, muscle strength) of the ICF, with only a small minority addressing activity limitations (eg, affecting activities of daily living) experienced by patients. A consideration of participation restrictions (eg, fulfillment of vocational roles) is almost wholly absent from the literature. Yet social role reintegration is of fundamental importance to patients. Further research is required in these two domains. The ICF provides a comprehensive framework for future research into rehabilitation interventions for STS.
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PMID:Rehabilitation and quality-of-life issues in patients with extremity soft tissue sarcoma. 1550 81

Perifosine (NSC 639966) is a synthetic, substituted heterocyclic alkylphosphocholine that acts primarily at the cell membrane targeting signal transduction pathways. Early clinical trials were limited because of dose-limiting gastrointestinal toxicity, and parenteral dosing of this class of agents is not possible because of their hemolytic properties; therefore, related compounds with an improved therapeutic index were developed. Toxicity was minimized and efficacy improved by using a loading dose/maintenance dose schedule, and therefore, this schedule was carried into clinical trials. This phase I trial enrolled 42 patients with incurable solid malignancies. The starting doses were 100 mg p.o. x four doses (every 6 hours) load followed by a 50 mg p.o. once daily maintenance dose with escalation of either component in successive dose levels. No treatment related deaths occurred. The maximum-tolerated dose was determined to be 150 mg p.o. x four doses load and 100 mg p.o. once daily maintenance. Dose-limiting toxicities such as nausea, diarrhea, dehydration, and fatigue were seen early during the loading phase and were surmountable with the use of prophylactic 5-HT3 receptor antagonists, dexamethasone, and loperamide. Toxicities during the chronic phase were difficult to manage and, given that pharmacokinetic data showed biologically active serum concentrations (based on preclinical data), raised the question of less frequent maintenance dosing. Pharmacokinetic data confirmed the maintenance of stable drug levels with chronic dosing and the long half-life. One partial response was seen, as were multiple patients with stable disease beyond course 2. These results suggest perifosine activity in sarcoma and perhaps renal cell carcinoma (stable disease in two patients who continued for 6 and 14 courses), thus justifying additional investigation of this agent in a phase II sarcoma trial.
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PMID:A phase I trial of perifosine (NSC 639966) on a loading dose/maintenance dose schedule in patients with advanced cancer. 1556 74

Aviscumine is a ribosome-inactivating protein with potent antitumour activity in vitro and in vivo and is an Escherichia coli-derived recombinant counterpart of natural mistletoe lectin-I. The current study was performed to determine the safety profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of a prolonged infusion of aviscumine in cancer patients. Aviscumine was given once weekly as a 24 h central intravenous infusion in patients with advanced, refractory progressive solid malignant tumours. Fourteen fully eligible patients (11 male, 3 female) with a median age 58 yrs (range 41-77) were enrolled. They had histologically verified disease, were 18 yrs old, had an ECOG PS 2 and adequate bone marrow, liver and renal function. DLT was defined as any non-haematological grade 3-4 toxicity (Common Toxicity Criteria [CTC] version 2.0), neutrophil count <500/ microl for 7 days, febrile neutropenia or thrombocytopenia grade 4. The MTD was defined as the dose level below the dose at which 2 patients per dose level experienced a DLT during the first treatment cycle. Colorectal cancer, soft tissue sarcoma and pancreatic cancer were the most common tumour types. Dose levels of aviscumine ranged from 4 to 6 microg/kg. The median number of cycles was 2.8 (range, 2-8). Common side effects in cycle 1 were fatigue, fever, nocturia, urticaria, erythema and pruritus. DLTs occurred in 2/3 patients on the 6 microg/kg dose level and consisted of increases in ASAT grade 3, ALAT grade 3, gammaGT grade 3/4, hypokalemia grade 3 and fatigue grade 3. No DLTs were observed on dose levels 4 and 5 microg/kg. The best response (RECIST) was stable disease in 4 pts, lasting for 4-8 cycles. Pharmacokinetics indicated that potentially active plasma levels of the compound were maintained during the entire infusion. We conclude that the recommended dose for weekly 24 h infusions of Aviscumine should be 5 microg/kg.
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PMID:Weekly 24 h infusion of aviscumine (rViscumin): a phase I study in patients with solid tumours. 1591 88

Histiocytic sarcoma is a rare neoplasm, and its aetiology is unknown. It is a malignant proliferation of neoplastic cells showing immunophenotypic and morphologic features similar to tissue histiocytes. The clinical course of histiocytic sarcoma is usually agressive. The signs and symptoms of histiocytic sarcoma are systemic symptoms (fever, weight loss), hepatosplenomegaly, adenopathies, intestinal obstruction, rash and pancytopenia. We present the case of a 75 years old woman, with fever, weight loss, anorexia, fatigue, splenomegaly and pancytopenia. Bone marrow examination showed the diagnosis of histiocytic sarcoma.
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PMID:[Histiocytic sarcoma: a case report and review of the literature]. 1600 16

The study aimed to assess the efficacy and safety of brostallicin, a new DNA minor groove binder, at a dose of 10mg/m2, intravenous (i.v.) every three weeks, in patients with advanced or inoperable soft tissue sarcoma (STS) and gastrointestinal stromal tumour (GIST) failing first line therapy. Two groups were recruited: (1) GIST following treatment with imatinib; (2) other STS following treatment with single agent doxorubicin or ifosfamide or a single line of combination therapy. The primary end-point was overall response rate (ORR) as defined by response evaluation criteria in solid tumours (RECIST). Progression free survival (PFS) was a secondary end-point. In the GIST group, a Simon two step design was planned: first step 18 patients, total 32 patients (p1=20% p0=5% alpha=beta=0.1). In the non-GIST group, planned sample size was 40 in a standard Fleming one-step design (p0=10%, p1=25%, alpha=beta=0.1). Forty-three patients with non-GIST and 21 patients with GIST were recruited. In general, the drug was well tolerated. Common Toxicity Criteria (CTC) grade 3 or grade 4 toxicity was granulocytopenia: 70% of patients, 50% of cycles; fatigue: 25% of patients, 8% of cycles; febrile neutropenia: 14% of patients, 4% of cycles. There was one confirmed toxic death due to neutropenic septicaemia. Three patients had clinically significant allergic reactions in 249 cycles delivered. In the GIST group, no patients had a confirmed response and recruitment was discontinued at the first step. In the non-GIST group, there were two confirmed partial responses. The 3 month PFS was 46% in the non-GIST group and 33% in the GIST group. In the non-GIST group, this PFS is in the range of other agents considered active in STS, and may predict for more substantial first line activity. Further investigation in STS other than GIST appears warranted.
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PMID:Brostallicin, an agent with potential activity in metastatic soft tissue sarcoma: a phase II study from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. 1709 9

Purpose. Flavopiridol is a potent cyclin-dependent kinase (CDK) inhibitor that has preclinical activity in many tumours. This synthetic flavonoid was tested in a phase II nonrandomized, nonblinded multicentre clinical trial to determine its activity and toxicity in patients with previously untreated metastatic or locally advanced soft tissue sarcoma. Methods. A total of 18 patients with histologically confirmed nonoperable soft tissue was treated with flavopiridol administered at a dose of 50 mg/m(2) IV over 1 hour daily x3 days every 3 weeks. Results. Eighteen patients were accrued to the study over a period of 6 months. No objective responses were noted in the seventeen evaluable patients. Eight patients (47%) exhibited stable disease after 2 cycles (median duration of 4.3 months (range 1.4-6.9 months). Kaplan-Meier estimates for 3- and 6-month progression-free survivial rates were 44 percent and 22 percent, respectively. The only grade 3 toxicities were diarrhea (N = 2), nausea (N = 2), gastritis (N = 1), and fatigue (N = 1). Ninety-four percent of patients received >/= 90% of the planned dose intensity, during 55 treatment cycles. Conclusions. Flavopiridol was well tolerated at the dose and schedule used in this study, however, no objective treatment responses were seen and thus our results do not support further exploration of flavopiridol as a monotherapy at this dose and schedule in soft tissue sarcomas.
Sarcoma 2006
PMID:A Phase II Study of Flavopiridol in Patients With Previously Untreated Advanced Soft Tissue Sarcoma. 1725 59

No standard treatment is established for patients with advanced soft tissue sarcoma after previous chemotherapy with anthracyclines and ifosfamide, given either in combination or sequentially. Exatecan (DX-8951f) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself, topotecan or irinotecan. Since some activity against soft tissue sarcomas, especially leiomyosarcomas, has been reported for topoisomerase I-inhibitors, a study with a new and more potent agent seemed justified. We report on a prospective multicentre phase II study of Exatecan in adult soft tissue sarcomas failing 1 or 2 lines of chemotherapy in advanced phase, performed within the STBSG of EORTC. Thirty-nine patients (16 leiomyosarcomas and 23 other histologies) were included in two independent strata and received a total of 141 cycles (median 2). Median age was 61 years, range 25-76. Exatecan was given as i.v. infusion over 30 min at a dose of 0.5mg/m2 every day for five consecutive days, repeated every 21 days. Seventy-four percentage of cycles could be given without dose or schedule modification. The main toxicity was haematotoxicity with grade 3/4 neutropenia in 49%, grade 3/4 thrombocytopenia in 23%, and grade 3/4 anaemia in 15% of patients, respectively. Non-haematological toxicity consisted mainly of grade 2/3 dyspnoea in 36% of patients and grade 2/3 fatigue in 28%. One treatment-related toxic death due to septic shock was reported. Best overall response was no change with 60% in the leiomyosarcoma group and 53% in the non-leiomysarcoma group, respectively. The 3 months progression-free survival estimates are 56% for leiomysarcomas and 26% for other histologies, respectively. Using a two-step statistical design, the trial was stopped after the first step in both strata, due to lack of activity. In pretreated soft tissue sarcoma patients, Exatecan is well tolerated but does not achieve any objective responses. However, with respect to progression-free survival, Exatecan did show some activity in leiomyosarcomas.
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PMID:Exatecan in pretreated adult patients with advanced soft tissue sarcoma: results of a phase II--study of the EORTC Soft Tissue and Bone Sarcoma Group. 1733 54

Pulmonary artery sarcoma is an exceptionally rare tumor which must be considered in the differential diagnosis of pulmonary thromboembolism. We report the case of a 36-year-old woman and review 100 cases published in the literature between 1988 and 2005. The patient presented with a history of dyspnea, fatigue, fever, night sweats and anemia that did not respond to antibiotic therapy. She also had hemoptysis. Transvenous catheter biopsy was indicative of sarcoma. A left pneumonectomy was performed, followed by five cycles of chemotherapy. Histological and immunohistochemical studies documented an intimal sarcoma with myofibroblastic differentiation. The patient is alive and well 20 months after surgery. The clinico-pathological features of pulmonary artery sarcoma are described.
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PMID:Pulmonary artery sarcoma: an insidious tumor still diagnosed too late. Analysis of the literature and report of a case. 1755 Jan 45

We report the case of a 51-year-old patient who presented with tiredness and leg swelling, with recurrent pericardial effusion; a right atrial tumor, suggestive of sarcoma, was diagnosed, which responded poorly to chemotherapy. In the absence of metastases, surgery for excision of the tumor was undertaken. Two months after surgery she had a new recurrence of pericardial effusion and chemotherapy was reinitiated. She is currently well and asymptomatic, with no signs of recurrence ten months after surgery and nearly 24 months after the initial diagnosis.
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PMID:Primary cardiac angiosarcoma. Extended resection of the right atrial wall. Case report. 1829 40

Purpose. The aims of this study were to describe the symptoms experienced by patients in the first year following treatment for lower extremity sarcoma by limb conservation and to describe the relationship between symptoms and physical disability.Subjects. Eighty consecutive patients treated for primary bone or soft tissue sarcoma (STS) of the lower limb who were treated with limb preservation surgery.Methods. Subjects were evaluated by questionnaire at 6 weeks, and 3, 6, and 12 months post surgery. They identified whether they experienced any of the following symptoms: pain, stiffness, fatigue, weakness, limited range of motion, or swelling.The Toronto Extremity Salvage Score (TESS), a measure of physical disability, was also completed. Frequency of symptoms over time was calculated and change was evaluated using the Cochrane test. The relationship of symptoms to disability was analyzed with regression methods.Results. The mean age was 43.0, SD=20.4 with a gender ratio of 1:1. There were 38 bone tumours and 42 STS.The most frequently reported symptoms were: stiffness 48 (60%), weakness 41 (51%), fatigue 26 (33%), and pain 25 (31%) at 6 weeks. Stiffness and fatigue decreased and plateaued by 3 months. Complaints of weakness and pain continued to decrease over time. At 6 weeks, pain, stiffness, weakness and limited motion predicted disability in both univariate and multivariate analyses. At 12 months, pain, stiffness, fatigue, weakness and limited motion were significant predictors of the TESS in univariate analysis with only pain, stiffness and limited motion significant predictors in the multivariate model.Discussion. Pain, stiffness, fatigue, weakness and limited motion are common symptoms with stiffness and weakness decreasing significantly over time. The symptoms predictive of disability differ between the acute and late phases of recovery.
Sarcoma 1999
PMID:Symptoms and their Relationship to Disability Following Treatment for Lower Extremity Tumours. 1852 Dec 66


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