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)

An autopsy case of malignant fibrous histiocytoma (MFH) of the mediastinum in a 25-year-old Japanese man is described. He initially complained of general fatigue and intermittent tarry stool, and was radiographically revealed to have a huge mass within the mediastinum as well as multiple nodules within the abdominal cavity, respectively. The mediastinal tumor could not be resected because of direct tumor invasion into surrounding tissues. Within the abdominal cavity, three distinct tumor nodules were discovered in the jejunum, which could be resected surgically. Histopathologically, the components of both lesions were very similar, and the present case was interpreted as multiple metastases of mediastinal MFH to the intestinal wall. In spite of various kinds of treatment, the mediastinal tumor rapidly enlarged, causing SVC syndrome. Brain CT findings suggested multiple metastases which were considered to be the cause of death. Autopsy confirmed that the main tumor nodule was located within the mediastinum, with brain metastases. The present case of mediastinal MFH is considered to be the youngest case as well as the first case presenting intestinal metastases.
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PMID:An autopsy case of malignant fibrous histiocytoma of the mediastinum, presenting multiple metastases to the small intestine and to the brain--a rare case report with a review of the literature. 217 6

Eight patients were treated with leukocyte interferon for a variety of neurological malignancies that had failed or recurred after conventional therapy. Three patients with malignant astrocytoma received intratumoral interferon in dosages up to 9 million units 3X/week, with total dosages of up to 160 million units. Interferon was administered intraventricularly in 4 patients with leptomeningeal metastases and one patient with multiple brain metastases. Dosages increased from 1 to 10 million units 3X/week, and total dosages of up to 113 million units were given intraventricularly. Acute side effects of fever, nausea, vomiting, and headache occurred almost exclusively with intraventricular injections, and these subsided after the initial injection. Fatigue, loss of appetite, weight loss, and hematologic toxicity developed a few weeks after onset of treatment, independent of the dose given. A modest tumor regression was seen on CT scans of one patient with a malignant astrocytoma, who was treated with interferon for 8 months. In all 4 patients with leptomeningeal metastases, the CSF became free of malignant cells for 6 to 10 weeks, while clinical improvement was less dramatic.
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PMID:Phase I clinical trial of intralesional or intraventricular leukocyte interferon for intracranial malignancies. 298 29

Based on the reports of activity of interferons against metastatic melanomas, we conducted a phase II study of recombinant interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ) in 66 patients with disseminated melanoma. All patients had excellent Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1), and no evidence of brain metastases. Thirty patients had previously received chemotherapy and the remainder were untreated. The first 35 patients were treated on a daily schedule starting with a Roferon-A dose of 3 X 10(6) U/d and escalating to a maximum of 36 X 10(6) U/d over a period of 12 days. Because of excessive toxicity, the second group of 31 patients were treated on a fixed dose of 18 X 10(6) U/d [corrected] three times weekly (TIW). Among the 62 evaluable patients, five achieved an objective response for a response rate of 8% (95% confidence limits, 3% to 18%). Four patients had minor regressions and eight patients had stability of disease. The responses were evenly distributed between the two dose schedules. The major toxicity of interferon consisted of a constitutional syndrome of anorexia, fever, weight loss, and fatigue, which required a dose reduction in 75% of the patients on the daily schedule. Our data revealed a modest level of activity, which was not influenced by prior treatment or by the dose or schedule of interferon. Because of substantial toxicity with the daily schedule, we recommend a dose of 18 X 10(6) U/d [corrected] if interferon is used in the treatment of patients with melanoma.
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PMID:Clinical evaluation of recombinant interferon alfa-2a (Roferon-A) in metastatic melanoma using two different schedules . 362 46

Polyinosinic-polycytidylic acid, a double-stranded ribonucleic acid that is a potent inducer of interferon production, was used in a stabilized form to treat 11 patients with metastatic renal cell carcinoma. Seven patients completed a full course of 8 infusions at maximum tolerated dosage. All patients experienced transient fever and marked fatigue. Anorexia was mild. Transient leukopenia occurred in 3 patients and reversible elevation in creatinine was observed in 1. All 4 patients with brain metastases became lethargic, and 3 died during or shortly after therapy. Only 2 patients demonstrated measurable total regression of isolated metastases (pleural/pulmonary in 1 and bone in 1) but in both metastases at other sites progressed. No partial regressions were seen. Metastases at all other sites (liver, brain and renal fossa) progressed during therapy. Patients who appeared to respond and who performed best during therapy generally demonstrated a higher performance status initially. Expression of natural cytotoxicity in in vitro testing did not correlate with a demonstrated response to treatment.
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PMID:Immunotherapy of metastatic renal cell carcinoma with polyinosinic-polycytidylic acid. 380 4

The Southwest Oncology Group entered 62 patients with Stage IV or inoperable Stage III (one patient) melanoma into SWOG protocol 8804 and treated them with cisplatin 100 mg/m2 and DTIC 750 mg/m2 i.v. infusion over 15-30 minutes. There were 18 patients with brain metastases and four ocular primaries. Five patients, all without bain metastases, were ineligible. Responses of 8 patients could not be determined, and 11 patients received only one course of treatment. Of the eligible patients, 46 (81%) had some hematologic toxicities, with 31 of these (67%) having grade III or worse. There were 23 patients (40%) with renal toxicities. The miscellaneous toxicities were muscle weakness, flu-like symptoms, and fatigue. Five patients died while on treatment. There were no complete responses. Eight patients had partial responses ranging from 1.5 to 10.5 months, although two patients were still alive at 30.4 and 30.9 months. The estimated response rate for patients with brain metastases was 11%. The estimated response rate for patients without brain metastases was 13%. If one unconfirmed partial response is included, the overall response rate is 14% with a 95% confidence interval of 6% to 26%. It is concluded that DTIC and cisplatin have definite activity in melanoma, but, at least in this population, the toxicity is treatment-limiting and requires close attention to patient care.
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PMID:Evaluation of cisplatin and DTIC in inoperable stage III and IV melanoma. A Southwest Oncology Group study. 832 16

Following a previous EORTC GU-Group study, in which linomide showed some activity in poor prognosis patients, this study was initiated to determine the effect of linomide in more favourable patients. 35 patients with metastatic renal cell carcinoma with good prognostic factors, i.e. good performance status, prior nephrectomy, no prior systemic therapy, and no liver, bone or brain metastases, were treated with linomide, a quinoline derivative with immunomodulating properties, at a dose of 10 mg daily, after an initial dose escalation during the first 4 weeks of treatment. In 29 evaluable patients, no responses were observed (95% confidence interval 0-10%). Best overall response was no change in 9 patients, for a median duration of 4 months. Linomide in this schedule was poorly tolerated, with 17% (6 patients) of patients being withdrawn and 23% (8 patients) having dose reductions due to adverse events, mostly influenza-like symptoms of myalgia, arthralgia and fatigue. Several cases of pericarditis and neuropathy were observed. In spite of selection of favourable prognosis patients and an optimal daily dosing schedule, linomide was not an effective treatment in renal cell carcinoma. In view of toxicity and lack of efficacy, there is no rationale in further testing the drug in this disease.
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PMID:EORTC phase II study of daily oral linomide in metastatic renal cell carcinoma patients with good prognostic factors. 915 37

High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% CI 14-3%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% CI 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage III disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis.
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PMID:Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD) plus interferon alpha for metastatic melanoma: a multicentre phase II study. 923 31

High-dose therapy with interleukin-2 (IL-2) can produce significant responses in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC). Several studies have shown the benefit of low-dose IL-2 in patients with RCC, but few studies have evaluated low-dose IL-2 in MM. We have used the following regimen: Interferon-alpha 10 million units subcutaneously on days 1, 3, 5, 8, 10, 12, 22, 24, and 26; and IL-2 60,000 IU/kg i.v. every 8 h on days 8-12 and 22-26. Patients had measurable MM or RCC and were excluded for ECOG status > 3, brain metastases, or significant cardiopulmonary or renal dysfunction. Between January 1993 and April 1996, 38 patients with MM and 14 with RCC were treated. In MM, there were six responses (15.7%; 95% confidence interval 4.1-27.3%) (i.e., one complete response and five partial responses). Responses were seen in visceral and nodal disease. Responses were of good duration: 40+, 26+, 13, 6, 4, and 3 months. One response was seen in the 14 RCC patients. Treatment was considerably less toxic than with high-dose IL-2. All treatment was given in a medical or surgical ward with intensive care necessary in only two patients. More than 80% of patients received > 80% of the predicted dose of IL-2. Dose-limiting toxicity consisted mainly of mild confusion or fatigue. In summary, this regimen is better tolerated and produces response rates within the range reported for high-dose IL-2 for patients with MM.
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PMID:Low-dose intravenous bolus interleukin-2 with interferon-alpha therapy for metastatic melanoma and renal cell carcinoma. 945 37

Interleukin (IL) 2 plays an important role in enhancing the immune response, whereas IL-4 has pluripotent activities which include affecting immune function. Preclinical data suggest that the combination might have enhanced immunomodulatory activity. In this Phase I trial in patients with advanced solid tumors, both IL-2 and IL-4 were given by separate s.c. injections simultaneously daily, 5 days in a row, Monday through Friday, for 3 consecutive weeks, followed by a 1-week break from treatment. Cycles could be repeated. The dose of IL-2 was kept constant at 9 x 10(6) IU/m2/injection while the dose of IL-4 was escalated beginning at 100 microgram/m2/injection and increasing by 100-microgram/m2 increments to a planned level of 400 microgram/m2/injection. Sixteen patients were entered in this study, with one patient being ineligible because of the presence of brain metastases. Of the 15 eligible patients, there were 14 males and 1 female, with a median age of 54 (range, 38-67) years and initial performance status of 0 in 5 patients and 1 in 10 patients. Patients were treated at levels of up to 300 microgram/m2/injection of IL-4 before the study was closed due to withdrawal of the drug by the manufacturer. The most commonly observed toxicities were fatigue, fever and chills, local reaction, nausea/vomiting and anorexia, headache and nasal stuffiness, and coughing, sometimes with the production of clear white sputum, more common in smokers. Duodenal ulcers occurred in one patient and one patient had grade 4 cardiac toxicity consisting of an asymptomatic minimal elevation of the creatinine phosphokinase MB isoenzyme (CPK-MB). Grade 3 hyponatremia occurred in two patients, and elevated liver function tests and creatinine occurred but were not dose limiting. Eosinophilia of unknown significance occurred in all patients. There were statistically significant elevations in absolute numbers of most T-cell subsets examined, without changes in circulating B cells. No antibodies to the IL-4 were found after one cycle. One patient with renal cell carcinoma showed a significant decrease in tumor burden after one cycle of treatment. Because of the IL-4 withdrawal, the maximum tolerated dose for this combination of drugs given by the route and schedule used here was not determined and will require additional testing. Subcutaneous IL-2 and IL-4 given simultaneously show important immunomodulatory and antitumor effects and should be tested further in cancer patients.
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PMID:Phase I trial of simultaneous administration of interleukin 2 and interleukin 4 subcutaneously. 981 6

Postoperative radiotherapy (RT) forms an intrinsic part of breast conservation therapy, substantially reducing the risk of breast relapse. It is given 4-6 weeks postoperatively using medial and lateral beams to achieve a near homogeneous dose to the breast while minimising the dose to adjacent structures. Typically, a dose of 40 Gy in 15 daily fractions over three weeks or 50 Gy in 25 fractions over five weeks is given, with a boost of 10 Gy using low energy electrons or superficial X-rays. RT is delivered to the chest wall after mastectomy in patients with large tumours (> 5 cm), close surgical margins, or significant axillary node involvement and may result in an additional 10% survival benefit. Early complications of RT include tiredness, skin erythema and moist desquamation. Late reactions, breast fibrosis, telangiectases and peau d'orange are reduced if more treatment fractions are given. Lung irradiation is minimised by careful treatment planning and < 1% of patients experience radiation pneumonitis or pulmonary fibrosis. Patients with locally advanced breast cancer may be offered a combination of systemic therapy, endocrine, chemotherapy and radical RT. Preoperative systemic and radiation therapy reduces the mastectomy rate but at present does not improve survival. Those who are unfit for radical treatment and have large ulcerating or fixed cancers are offered either endocrine or cytotoxic therapy, depending upon the oestrogen receptor status, followed by RT, which is unlikely to cure but may achieve local control for a variable duration. RT forms part of the multidisciplinary approach to palliative treatment for metastatic disease. Bone metastases occur in 75% of women with metastatic disease and RT provides effective pain relief and reducing risk of pathological fractures. Patients with brain metastases need high-dose steroids followed by cranial RT.
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PMID:Radiotherapy for early and advanced breast cancer. 1177 Mar 58


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