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)

Since cytotoxic chemotherapy (BCNU, DTIC and cisplatin, tamoxifen) and interferon-alpha (IFN-alpha) have each produced responses in advanced malignant melanoma, a phase II trial was conducted to evaluate the response and toxicity of simultaneous administration of both therapies. Of 33 assessable patients, two (6%) had complete response (CR) and 12 patients (36%) had partial response (PR), for a total response rate (CR+PR) of 42% (95% confidence interval 26-58). Four patients had minor response (12%). Mixed responses occurred in five patients (15%). The remaining patients had progressive disease. The duration of CR was 3, 7 and 17 (+) months and the duration of PR was 3+ to 19+ months (median 6 months). The median overall survival for all patients entered into the study was 5 months. Main toxicities included myelosuppression and fatigue. Combined simultaneous cytotoxic chemotherapy and IFN produced a high response rate (42%) which is comparable to that reported for chemotherapy alone. Further studies are needed to determine the optimal schedule for combining chemotherapy and immunotherapeutic agents as well as the impact of biological agents on survival in the treatment of melanoma.
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PMID:Phase II trial of recombinant interferon-alpha with BCNU, cisplatin, DTIC and tamoxifen in advanced malignant melanoma. 749 64

Several clinical trials have demonstrated that granulocyte colony-stimulating factor (G-CSF) accelerates the recovery of neutropenia in chemotherapy-induced bone marrow suppression. In this report, we describe a 46-year-old female with glioblastoma multiforme who developed interstitial pneumonia due to administration of G-CSF during the phase of immunochemoradiotherapy-induced neutropenia. Thirty-three days after starting immunochemoradiotherapy (ACNU, VCR, IFN -beta, radiation), she developed neutropenia (1,000/microliters). Administration of G-CSF at doses of 125-250 micrograms/day led to an increase of peripheral neutrophil counts. Eleven days later, the patient developed sudden severe respiratory failure and cyanosis with worsening of lung shadows. Blood gas levels on room air were PaO2 49.3mmHg, PaCO2 28.0mmHg, and pH 7.46. At this time, her neutrophil count had risen to 26,080/microliters. LDH and alpha - HBD had also increased to 1,439 IU/l and 1,117IU/l respectively. Chest radiograph and CT scan demonstrated interstitial pneumonia. After treatment with methyl prednisolone, her respiratory symptoms were gradually resolved. A number of side-effects have been reported with granulocyte-macrophage colony-stimulating factor (GM-CSF). These include fluid retention with pericardial and pleural effusion, fever, bone pain, fatigue, and rash. This report also suggests that G-CSF might be a cause of interstitial pneumonia during the phase of immunochemoradiotherapy-induced neutropenia.
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PMID:[A case report of interstitial pneumonia caused by granulocyte colony-stimulating factor]. 750 62

A 68-year-old man who was admitted to our hospital because of general fatigue and anorexia. He was diagnosed as suffering from neuron specific enolase (NSE)-producing IgD-lambda type multiple myeloma with high activity of serum amylase, based on the detection of monoclonal IgD-lambda M-protein in the serum and urine, markedly high activities of salivary-type amylase and NSE in the serum, and immunohistochemical evidence of NSE and IgD in the myeloma cells. After two courses of alpha-IFN and VMCP chemotherapy, serum IgD, amylase and NSE decreased to normal levels. These observations indicate that NSE was ectopically produced by myeloma cells.
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PMID:[Neuron specific enolase-producing IgD multiple myeloma with high serum amylase activity]. 754 Feb 26

In 1988, a prospective, randomized multicenter study was initiated to determine the efficacy of a combined induction regimen with recombinant interferon-alpha-2b (IFN-alpha) and maintenance with IFN-alpha on the response and survival rates in multiple myeloma (MM) patients. Induction therapy consisted of VMCP (vincristine, melphalan, cyclophosphamide, prednisone), randomized to combine IFN-alpha at a dose of 2 x 10(6) U, 5 days per week throughout the induction period of 12 months. Patients who achieved plateau phase were subsequently randomized again between IFN alpha maintenance (2 x 10(6) U, 3 days a week) for 12 months and no maintenance therapy. Of the previously untreated patients, 84 were initially randomized for induction therapy, and 31 for the maintenance phase with IFN-alpha. Results of the cohort median survival, based on the intention to treat, have shown that those on the VMCP/IFN-alpha arm had a median survival of 53 months, compared with patients on the VMCP induction arm who a median survival of 26 months (P = 0.052). The median survival of stage 3 evaluable patients who were on the VMCP/IFN induction arm was 43 months, and 13 months for patients treated by VMCP alone (P = 0.008). No significant difference in survival was detected among patients in partial remission (after induction) who had a second IFN-alpha randomization at the plateau phase. Hematologic toxicity, mild to moderate fever, and fatigue were more common in the VMCP/IFN induction arm. The results show that VMCP/IFN is a well-tolerated treatment regimen, and is superior to VMCP for patients with stage 3 myeloma.
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PMID:Interferon-alpha-2b with VMCP for induction in multiple myeloma: the Israel Myeloma Cooperative Group experience. 759 91

The prognosis and the quality of life of patients with carcinoid tumors is related either to symptoms from the substances secreted or to progressive tumor growth. Medical treatment with cytotoxic agents is of marginal value for increasing life expectancy and reducing clinical symptoms. Recent studies with interferon have shown interesting results. In the present investigation, 22 patients with carcinoid tumors and syndrome were treated with recombinant interferon alpha-2a (r-IFN alpha-2a) at the dose of 6 x 10(6) IU intramuscularly daily for 8 weeks and three times weekly thereafter. The primary tumor was localized in the foregut (n = 11), midgut (n = 7), hindgut (n = 1), and unknown site (n = 3). Most cases had liver metastasis. Seventeen patients had elevated 5-hydroxyindoloacetic acid (5-HIAA) excretion and 5 had flushing and/or diarrhea as the only clinical manifestation. Six cases presented a complete syndrome (flushing, diarrhea and 5-HIAA excretion). Control of symptoms was obtained in 80% and a 5-HIAA level reduction in 58% of the patients. The interferon treatment was more effective for control of the carcinoid syndrome than for control of tumor growth. The treatment was well tolerated and fever, myalgia, anorexia and fatigue were the most frequent side-effects.
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PMID:Treatment of carcinoid syndrome with recombinant interferon alpha-2a. 768 66

A 69-year-old woman visited our hospital with complaints of low grade fever and general fatigue in October 1990. Computed tomography (CT), ultrasonogram, and renal arteriography showed left renal tumor and she was diagnosed with renal cell carcinoma (T2M0N0). Left radical nephrectomy was performed in December 12, 1990. After operation, 3 x 10(6) unit per day of IFN-alpha were administered three times per week. She complained of low grade fever and general fatigue in June, 1991. CT showed left lung metastasis (phi 3 cm). She was given combined chemotherapy (MVP: methotrexate, vinblastine, pepleomycin). After 2 courses, lung metastasis decreased and after 4 courses, lung metastasis was not shown by CT in December, 1992. No evidence of relapse was shown by CT in June, 1994.
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PMID:[A case of lung metastasis from renal cell carcinoma showing complete response by a combination chemotherapy with methotrexate, vinblastine and pepleomycin (MVP)]. 774 Oct 73

A six-year history of repeated attacks of fatigue, fever, arthralgias, skin changes, Raynaud's phenomenon, and neuropathy is reported in a patient with chronic liver disease. The following diagnoses were made: (1) leukocytoclastic vasculitis; (2) acute urticaria; (3) cryoglobulinemia type II with Raynaud's phenomenon and low serum level of C4; (4) peripheral polyneuropathy; (5) sicca syndrome; and (6) chronic hepatitis C virus infection. Despite therapy with corticosteroids symptoms increased gradually over years. In the first PCR of the nested PCR analysis, HCV-RNA was exclusively detected in the cryoglobulin fraction but not in the serum supernatant, suggesting that antibodies bind HCV particles, forming circulating immune complexes. As diagnoses 1-5 are well-known organ manifestations of cryoglobulinemia, we speculated whether treatment of hepatitis C with IFN-alpha (3 million IU IFN-alpha 2b three times a week) would inhibit HCV replication, decrease the cryocrit level and thereby ameliorate organ manifestations such as neuropathy and vasculitis. During treatment with IFN-alpha only a very weak or no signal could be detected for HCV-RNA in the cryoglobulin fraction as well as in the serum supernatant. This held true also for the serum supernatant in the second PCR. In parallel, cryoglobulin level, immunoglobulins, and liver enzymes decreased substantially to normal or near normal levels. Clinical symptoms-leukocytoclastic vasculitis and neuropathy-disappeared. We conclude that chronic HCV infection is involved in the pathogenesis of cryoglobulinemia and that IFN-alpha might be an effective treatment in these patients.
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PMID:A role for chronic hepatitis C virus infection in a patient with cutaneous vasculitis, cryoglobulinemia, and chronic liver disease. Effective therapy with interferon-alpha. 778 36

Neuroendocrine gut and pancreatic tumors are neoplasms that present distinct features from other malignant tumors. Firstly, in most patients, tumor growth is rather slow, and even in advanced metastatic disease, there is very little impairment of the general well-being of the individual, e.g. appetite and weight. Secondly, these tumors are known to produce specific peptide hormones which may be factors in some clinical conditions e.g. carcinoid, Zollinger-Ellison and hypoglycemic syndromes. These conditions can be critical to the patients and can occasionally be lethal. Therefore, the treatment of neuroendocrine tumors must control the clinical symptoms related to hormone over-production and prevent further tumor growth. These two features are not always in parallel. Systemic treatment of neuroendocrine tumors mainly consists of chemotherapy, interferon and somatostatin analog administration. Chemotherapy has been used for at least 30 years; the most effective combination has proved to be streptozotocin with 5-fluorouracil or adriamycin. This combination produces biochemical responses in up to 60% of patients with endocrine pancreatic tumors; the results in carcinoid patients are very poor and response rates are < or = 10%. Alpha-interferon (IFN-alpha) produces biochemical responses in approximately 50% of patients with malignant carcinoid tumors, significant reductions in tumor size in 15% and a further 39% of patients have disease stabilization with no further tumor growth. Somatostatin analogs have only been used clinically within the last 10 years, but produce symptomatic improvement in 70% of cases, biochemical responses in 40-60%, but rarely produce any significant reduction in tumor size. These analogs are particularly useful to control severe clinical symptoms and are the first-line therapy for the management of carcinoid patients both peri- and intra-operatively. Patients with endocrine pancreatic tumors, particularly those with glucagon and vasointestinal peptide-producing tumors, benefit most from this type of treatment. Recently, a combination of IFN-alpha and a somatostatin analog has showed an additive effect of these two drugs. The side effects of streptozotocin and 5-fluorouracil are mainly nausea and vomiting which can be controlled with 5-HT3 receptor blocker therapy. Another significant adverse reaction is impaired renal function. The adverse reactions to IFN-alpha are mainly flu-like symptoms, fatigue, mild impairment of liver and bone marrow function and autoimmune reactions in 15% cases. Somatostatin analog treatment causes a low frequency of adverse reactions, those which do occur include gall stone formation and steatorrhea. Future systemic treatment should be based on increased knowledge of the tumor biology, particularly growth-regulatory mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine tumors of the gastrointestinal tract: systemic treatment. 785 82

To determine the maximum tolerated dose (MTD) of escalating doses of interferon-alpha-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisplatin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), colorectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder (1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c. on days 1-5 and then three times weekly with DDP (75 mg/m2, day 1) and 5-FU [750 mg/m2, days 1-5, continuous infusion (CI) on a 28-day cycle. The first two patients treated at level I (3 x 10(6) U/m2 s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accident (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 toxicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those with prior exposure to DDP. This resulted in grade 3 toxicity in terms of nausea, vomiting, fatigue and leukopenia but in no further CNS event. All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The recommended dose of IFN is 2 x 10(6) U/m2 s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m2, days 1-5, CI) and DDP (75 mg/m2, day 1) on a 28-day cycle.
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PMID:A phase I study of recombinant human interferon alpha-2b combined with 5-fluorouracil and cisplatin in patients with advanced cancer. 788 58

In the present paper we described the first case report of silent thyroiditis following alpha-interferon (IFN-alpha) treatment for chronic type C hepatitis in Japan. A 51-year-old woman with chronic type C hepatitis was treated with 6 million units of IFN-alpha three times a week for 24 weeks. Thyroid function was within normal limits and thyroid autoantibodies were negative before IFN therapy. Sixteen weeks after initiation of the treatment, she complained of increasing fatigue, palpitation and losing 7 kg in weight. Thyroid function tests at that time revealed an increase in serum T3, T4, free T3 and free T4 and a markedly suppressed TSH concentration. Both antithyroglobulin antibody (TgAb) and antimicrosomal antibody (McAb) were positive in a dilution of 1: 400. The computed tomographic (CT) scan of the thyroid showed a decrease in the CT number (Hounsfield unit; H.U.) to 58 H.U. (normal, 95-167 H.U.). The 24-h thyroid uptake of 123I was 0.75%. Aspiration biopsy specimens from a nodule in the right lobe and the remaining struma disclosed papillary adenocarcinoma and Hashimoto thyroiditis, respectively. Thyroid function spontaneously returned to normal two months after the onset of thyrotoxicosis through the subclinical hypothyroid stage. After recovery of thyroid function, patient had an operation of papillary cancer without any complications. These clinical features and laboratory findings led to the diagnosis of silent thyroiditis developing in the course of the long-term IFN therapy, which, to our knowledge, has not been reported before in Japan.
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PMID:An episode of silent thyroiditis in a patient with chronic thyroiditis and papillary adenocarcinoma following alpha interferon treatment for hepatitis C. 792 Aug 83


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