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)

A sixty-two-year-old man was admitted to our hospital for diarrhea and fatigue on September 1, 1988. Laboratory examination revealed anemia and a high serum protein level with increased gamma-globulin. Although he had no apparent bony lesions, the bone marrow picture showing an increase of abnormal plasma cells and serum immunoelectrophoresis indicating the presence of monoclonal protein of IgG-gamma type were compatible with multiple myeloma, stage IIIA. None of the following combinations of interferon alpha and ranimustine, cyclophosphamide and prednisolone, or melphalan and prednisolone were effective in reducing the level of serum M-protein. Therefore, we started daily oral administration of etoposide (25 mg/day) on February 21, 1989. Then the serum M-protein level was gradually reduced, and partial remission was achieved after 9 months' administration. After 27 months treatment the regimen was changed from daily to every second day administration, and finally stopped after 40 months. The patient has been in remission without etoposide to date.
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PMID:[A case of refractory multiple myeloma effectively treated with long-term oral etoposide]. 845 92

Chronic hepatitis C is a common cause of viral liver disease in kidney transplant recipients. To assess the efficacy and the safety of therapy with interferon alpha (IFN alpha) in such a population we conducted a prospective study where 16 kidney transplant recipients with chronic hepatitis C received recombinant IFN alpha 3 million units three times weekly scheduled for 24 consecutive weeks. All the patients had stable renal function for at least 1 year (mean serum creatinine 125.4 +/- 41 mumol/l). Fifteen patients had a positive HCV viraemia at the beginning of the study. In 15 patients serum alanine aminotransferase (ALT) levels decreased rapidly and normalized (48 +/- 44 vs 98.5 +/- 46 IU/l; P = 0.0044). ALT remained in the normal range as long as IFN alpha was continued. Serum levels of gamma glutamyl transpeptidase decreased from 129.75 +/- 111.2 to 88 +/- 85 IU/l; P = 0.012). After discontinuation of IFN alpha therapy seven responders relapsed within 1-9 weeks. HCV viraemia assessed 1 month after the end of IFN alpha therapy remained positive in all the patients who scored positive at the beginning, i.e. 15. Side effects of IFN alpha (fatigue, anorexia, weight loss) were frequent leading to four patients dropping out of the study. The haematological tolerance was moderate. The major concern was the increase in serum creatinine (162.5 +/- 57.6 vs 125.4 +/- 41 mumol/l; P < 0.05). In fact only six patients experienced renal failure occurring 45-168 days after the beginning of IFN alpha. Kidney transplant biopsies showed oedema, scarce scattered interstitial inflammatory cellular infiltration and moderate mesangial hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preliminary results of treatment of chronic hepatitis C with recombinant interferon alpha in renal transplant patients. 852 7

Twenty one patients with Philadelphia chromosome positive CML were treated with natural interferon alpha. All patients were in the chronic phase, 5 were untreated and 16 had been previously treated with busulfan or hydroxyurea. Eight patients in complete remission (CR) were given IFN subcutaneously at a dose of 5 x 10(6) unit per day as maintenance therapy, whereas 13 non-CR patients were given 2. 5 approximately 10 x 10(6) units for remission induction. Doses and intervals of IFN were adjusted to maintain the WBC count below 5 x 10(9)/l, but additional drugs were given when the WBC count could not be controlled with IFN alone. Six out of 10 evaluable non-CR patients attained CR with IFN only and 4 others achieved with additional drug. Cytogenetic responses were evaluated in 15 patients. CCR, PCR and MCR were attained in 5, 2 and 1 patients respectively. Southern blotting method showed that the BCR gene rearrangement disappeared in 5 out of 13 patients. Cytogenetic response rate was not different between untreated and previously treated patients, however it differed between patients with or without additional drug. The time to first cytogenetic effect was within 12 months in almost all effective cases. Fever and general fatigue were seen in almost all patients. IFN administration was discontinued only patients with severe skin eruption (3 patients) and bone marrow aplasia (1 patient).
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PMID:[Natural interferon alpha for chronic myelogenous leukemia in the chronic phase: hematologic, cytogenetic and molecular response]. 853 23

In a Nordic multi-centre trial, 583 previously untreated multiple myeloma patients were randomized to receive melphalan-prednisone or melphalan-prednisone+ interferon alpha-2b at a dose of 5 million units subcutaneously, 3 d/week. A quality-of-life study was integrated into the trial, using the EORTC QLQ C-30 questionnaire supplemented with 11 questions concerning interferon toxicity. The questionnaire was completed prior to treatment and after 1, 6, 12, 24, 36 and 48 months. 90% of the patients participated in the quality-of-life study, and 83% completed all questionnaires submitted to them. During the first year of treatment the patients on interferon reported significantly more fever, chills, dry skin, fatigue, pain, nausea/vomiting and appetite loss than the control patients. There was a moderate reduction of the global quality-of-life score and slight, non-significant, reductions of physical, emotional, cognitive, social and role functioning scores. After the first year there were no statistically significant differences in any toxicity, symptom or quality-of-life score, except for an increased frequency of dizziness in the interferon group. As only 60% of the patients remained on interferon after 24 months, our data probably underestimate the potential toxicity of the drug. Although there was no significant survival benefit for the interferon patients, a 5-6 months prolongation of the response and plateau phase duration was observed. However, by intention-to-treat analysis, there was no late quality-of-life benefit for the interferon patients to compensate for the early impairment. Thus, the clinical significance of the plateau-phase prolongation is uncertain.
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PMID:Effect of interferon on the health-related quality of life of multiple myeloma patients: results of a Nordic randomized trial comparing melphalan-prednisone to melphalan-prednisone + alpha-interferon. The Nordic Myeloma Study Group. 875 93

Measurement of health-related quality of life was integrated into a randomized trial (NMSG 4/90) comparing melphalan/prednisone to melphalan/prednisone + interferon alpha-2b in newly diagnosed multiple myeloma. One of the aims of the study was to assess the prognostic significance of quality-of-life scores, using the EORTC QLQ-C30 questionnaire. Univariate analysis showed a highly significant association with survival from the start of therapy for physical functioning as well as role and cognitive functioning, global quality of life, fatigue and pain. In multivariate analysis, physical functioning and W.H.O. performance status were independent prognostic factors (P values = 0.001 for both) when analysed in a Cox regression model with the somatic variables beta-2 microglobulin, skeletal disease and age. The best prediction for survival from the start of therapy was obtained by combining the beta-2 microglobulin and physical functioning scores in a variable consisting of three risk factor levels with an estimated median survival of 17, 29 and 49 months, respectively. At a 12 months landmark analysis, the relative risk for patients with physical functioning score 0-20 v 80-100 was 5.63 (99% CI 2.76-11.49), whereas the relative risk for patients without an objective response to chemotherapy compared to those with at least a minor response was 2.32 (99% CI 1.44-3.74). Quality-of-life assessment may be an independent and valuable addition to the known prognostic factors in multiple myeloma.
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PMID:Health-related quality of life assessed before and during chemotherapy predicts for survival in multiple myeloma. Nordic Myeloma Study Group. 913 39

The aim of this study was to investigate the possible therapeutic effect of 13-cis-retinoic acid plus interferon alpha-2a in patients with inoperable squamous cancer of the esophagus. Patients with advanced, measurable, histologically confirmed squamous carcinoma of the esophagus with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 who had adequate bone marrow, liver, and renal function were eligible for study. Patients were given cis-retinoic acid 1 mg/kg/day per mouth continuously and interferon alpha-2a 3 Mu/day for 3 days followed by 6 Mu subcutaneously daily thereafter. Seventeen patients were entered on study. Fifteen patients were evaluable for toxicity. The most common toxicities were grade 1 and 2 cheilitis, dry skin and flu-like symptoms which occurred in all patients. Two patients had grade 3 toxicity (1 anorexia and 1 fatigue). No grade 4 toxicity occurred. Fifteen patients were evaluable for response. No objective response was documented. The median survival time was 15 weeks. With no response seen it is unlikely that the combination of treatment as used in this study will be of benefit in patients with advanced squamous cancer of the esophagus.
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PMID:13-Cis-retinoic acid and interferon alpha-2a in patients with advanced esophageal cancer: a phase II trial. 915 75

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

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Roferon-A, Roche) (n = 12) or placebo (n = 8) every other day for 6 months and followed up for a further 6 months after stopping treatment. Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment. rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect profile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type I interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type I IFN therapy.
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PMID:Long term recombinant interferon alpha treatment in MS with special emphasis to side effects. 934 19

Interferons alpha and beta have been reported to cause tumor regression in a small proportion of patients with recurrent glioma. Eflornithine, an irreversible inhibitor of ornithine decarboxylase, reduces cellular polyamine levels and has also been reported to cause tumor regression in patients with recurrent anaplastic astrocytoma and glioblastoma multiforme. In vitro evidence suggests that interferon and eflornithine are synergistic. In this phase II trial, we investigated the combination of recombinant alpha interferon (36 x 10(6) units/m2 subcutaneously days 3 to 7) and eflornithine (2.25 g/m2 QID PO days 1 to 7) repeated every 28 days. All 29 patients entered in the study were evaluable for toxicity and efficacy. Toxicity consisted primarily of fever, chills, myalgia, weakness and fatigue as well as cortical dysfunction including somnolence, confusion, and exacerbation of underlying neurologic deficits. One patient died from cerebral herniation attributable to interferon. None of the patients experienced objective tumor regression. Seven patients (24%) were stable for more than six months, but the disease stability could also be explained by indolent underlying disease or inability to distinguish recurrent tumor from delayed radiation effects. Intermittent high-dose recombinant interferon alpha plus eflornithine demonstrated no definite antitumor effects in this trial.
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PMID:Phase II trial of recombinant interferon-alpha-2a and eflornithine in patients with recurrent glioma. 952 27

Interferon-alpha has been used to treat advanced renal cell carcinoma, and megestrol acetate has been shown to improve the quality of life of patients who have cancer. We combined interferon alpha-2b, 10 million IU/m2 subcutaneously 5 consecutive days per week, with megestrol acetate, 80 mg orally twice a day, in 15 patients who had advanced renal cell carcinoma. Only 6 (40%) had a prior nephrectomy, and most had disease in the lung and other sites. There were no complete or partial responders to this treatment, although stable disease was achieved in 5 (33%) patients. The treatment was excessively toxic, with 12 (86%) patients requiring dose modification or discontinuation of treatment due to fatigue. We conclude that interferon alpha-2b and megestrol acetate is an excessively toxic, inactive regimen, at least in a group of patients who have advanced disease with a poor prognosis.
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PMID:Interferon alpha-2b and megestrol acetate in the treatment of advanced renal cell carcinoma: a phase II study. 953 14


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