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)

Thirty-four patients with previously untreated advanced non-small-cell lung cancer were treated with a combination of polychemotherapy and recombinant interferon. Chemotherapy consisted of cyclophosphamide, 400 mg/m2, epidoxorubicin, 50 mg/m2, and cisplatin, 40 mg/m2 (CAP) i.v. on day 4; recombinant alpha 2b interferon (r alpha 2b IFN) was given i.m. daily at the dose of 3-5 MU from days 1 to 7. The treatment was repeated every 4 weeks. In the 32 eligible patients the overall response rate was 19.3% (95% C.L. 7.4-37.4%). Non-hematologic toxicity consisted formerly in flulike symptoms and fatigue complained of by 37.5% and 31.2% of patients, respectively, and vomiting reported in 68.7% of patients; grade III-IV myelotoxicity was observed in 12.5% of cases. In no case was the toxicity life threatening. The median overall actuarial survival and progression-free survival were 37 and 20 weeks, respectively. This study indicates that the combination of CAP chemotherapy and r alpha IFN is feasible and active in the treatment of advanced non-small-cell lung cancer.
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PMID:Combination chemotherapy and interferon alpha 2b in the treatment of advanced non-small-cell lung cancer. The Italian Lung Cancer Task Force (FONICAP). 185 86

Malignant carcinoid tumors with the carcinoid syndrome has over the years presented a therapeutic challenge. Surgery is the treatment of choice in local disease but when liver metastases have developed other treatment procedures must be considered. Conventional chemotherapy has been of little benefit, whereas a new somatostatin analogue octreotide gives a good control of clinical symptoms but not of tumor progression. Interferon treatment was introduced in 1982 by our group and we are now presenting results of medical treatment in 130 patients with histologically verified malignant carcinoid tumors and liver metastases. One hundred and eleven patients were treated with alpha-interferon, whereas 19 patients received conventional chemotherapy. Forty-seven out of 111 patients (42%) treated with alpha-interferon demonstrated a significant biochemical response and 15% also more than 50% reduction of tumor size. In another 43 (39%) patients stabilization of the carcinoid disease was noted whereas 21 (19%) showed progressive disease. The median duration of response was 34 months. Subjective response with improvement of diarrheas, flush and/or bronchoconstriction was noticed in 76 patients (68%). Among the 19 patients treated with conventional chemotherapy only 2 showed biochemical response and it lasted only for 3-5 months. The patients treated with chemotherapy had a median survival of only 8 months compared with 80+ months in the group treated with alpha-interferon. The adverse reactions of alpha-interferon are manageable and consist mainly of fatigue, weight reduction and reduction of blood cell counts. Neutralizing interferon antibodies might occur in patients treated with recombinant alpha-interferons (5-15%).
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PMID:The role of interferons in the management of carcinoid tumors. 185 9

We have successfully treated multiple myeloma of IgD (lambda) type [IgD (lambda) -MM] by natural alpha-interferon (alpha-IFN) single therapy. A 45 year-old man was admitted to Tokyo Medical College Hospital because of general fatigue in August, 1989. Immunoelectrophoresis, bone marrow biopsy and systemic bone survey revealed IgD (lambda) -MM with Bence Jones (BJ) proteinuria and slightly osteolytic lesions. We started treating him with natural alpha-IFN single therapy. Three months later, serum IgD markedly decreased and BJ proteinuria disappeared. Bone marrow, which had been packed with myeloma cells at the admission, was almost replaced by normal hematopoietic cells. In April 1990, he is still free of disease with only alpha-IFN single therapy. This result might suggest that alpha-IFN single therapy is effective for IgD-MM.
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PMID:[The successful use of natural alpha-interferon single therapy in multiple myeloma of IgD (lambda)-type]. 190 71

Recombinant alpha-interferons are used as therapeutic agents in an increasing number of benign and malignant disorders. Long-term administration of recombinant alpha-interferon as a maintenance agent is associated with a small number of adverse side-effects which are responsible for patient intolerance of this drug. These include weight loss, alopecia and chronic fatigue, anorexia and depression syndrome. This latter syndrome needs to be distinguished from thyroid disease, which is documented in this report in a number of patients on recombinant alpha-interferon therapy.
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PMID:Recombinant alpha-interferons, thyroid irradiation and thyroid disease. 190 80

Recombinant interleukin 2 (IL-2) is a potent inducer of lymphokine-activated killer (LAK) activity directed against autologous and allogeneic tumors; these effects are mediated by CD3-negative, CD56-positive, and CD16-positive lymphocytes. Although IL-2 therapy has been associated with clinical responses, particularly in patients with renal cell carcinoma and melanoma, these responses have occurred with high, toxic doses of this cytokine. Since gamma-interferon (IFN-gamma) potentiates LAK activity in vitro and in animal models, we initiated a dose-escalating Phase I trial of IFN-gamma and IL-2 in patients with advanced cancer. Patients were treated three times weekly (Monday, Wednesday, and Friday) for 6 weeks with bolus injections of IL-2; each dose was preceded 2 h earlier by a s.c. injection of IFN-gamma. Patients were treated with IFN-gamma at 0.01, 0.05, 0.1, or 0.25 mg/m2/dose. At each IFN-gamma dose, cohorts of at least three patients were treated with IL-2 at 1, 2.5, 5.0, or 7.5 x 10(6) Cetus units/m2 dose. Patients with clinical responses continued therapy three times weekly, while those with stable disease at 6 weeks were then treated twice weekly. A total of 41 patients were treated, all with Eastern Cooperative Oncology Group performance status 0 or 1. All patients were evaluable for toxicity. Dose-limiting toxicities were cumulative fatigue and constitutional symptoms. One documented transmural myocardial infarct occurred. The maximally tolerated dose combination, based on analysis of IL-2 dose intensity, was 0.1 mg IFN-gamma/m2 and 7.5 x 10(6) Cetus units IL-2/m2 per dose. Two partial responses and two minor responses were observed. Treatment was not associated with dose-associated changes in peripheral blood lymphocyte phenotype, but there was a trend favoring IFN-gamma dose-associated rises in IL-2 induction of natural killer and LAK activity by treated patients' lymphocytes. Analysis of the cumulative effects of therapy on induction of natural killer and LAK activity by measurement of the median area under the curve of activation showed clear evidence of IFN-gamma and IL-2 dose-associated changes. The IL-2 dose effects on cell lysis were monotone, while the optimal IFN-gamma dose appeared to be 0.1 mg/m2/dose, with a bell-shaped dose-response curve described previously for other effects of this cytokine. Using this novel statistical method of evaluating the biological effects of treatment, the optimal biological dose was identical to the maximally tolerated dose.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phase I evaluation of combination therapy with interleukin 2 and gamma-interferon. 190 79

To determine the effect of a recombinant alpha interferon 2b (Intron-A) and possible benefit of prednisolone pretreatment in chronic non-A, non-B hepatitis, 75 Chinese patients with clinico-histologically proven chronic hepatitis were randomly allocated to one of the following regimens: (A) 3 million units of Intron-A trice weekly for 6 months; (B) dose titration according to ALT-AST values; (C) prednisolone withdrawal followed by regimen A; (D) control group: no treatment for 6 months but followed by alternating treatment with 3 million units of Intron-A trice weekly for 2 weeks followed by 2 weeks no treatment for 6 months. Up to September 30, 1990, 67 patients have been followed for a minimum of 2 months. At the end of the second month, complete response (normal ALT) was achieved in 71% of group A, 50% of group B, 50% of group C and 0% of group D. At the end of the 6th month, the complete response rate was 62%, 47% and 64% respectively in groups A, B and C. The response rates in groups A and C were significantly better than the 7% in the control group. Complete response usually (91%) occurred within 2 months after the first dose of interferon. Relapse occurred in 40% of the complete responders, usually within 2 months of the last dose. The cumulative relapse rate was significantly lower in responders of group C (11% vs 43% in group A and 86% in group B during a period of 6 months). Only mild adverse effects were reported though two patients withdrew because of intolerable fatigue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prednisolone withdrawal followed by recombinant alfa-interferon in chronic non-A, non-B hepatitis: interim results of a randomized controlled trial. 190 74

A combination of oral zidovudine (250 mg twice daily) and subcutaneous interferon-alpha (10 x 10(6) units daily) was evaluated for clinical, antiretroviral, and immunological efficacy and for side effects in 17 patients with AIDS-related Kaposi's sarcoma. Fifteen patients were evaluable. During the study period of 12 weeks, tumor responses were complete in two patients and partial in two patients (27% major response rate). Minimal responses were seen in two patients (40% overall response rate). An anti-HIV effect (reduction of serum p24 antigen by 70% or more) was observed in seven of ten evaluable patients who were initially antigenemic. CD4 lymphocyte counts remained unchanged. In six patients who had either a tumor response or a marked decline of HIV antigenemia, the treatment was continued between 12 and 59 weeks beyond the study period. Two of four patients with tumor regression at 12 weeks had an additional tumor response in this period despite prior dose reduction of interferon due to toxicity. Late progression of KS was eventually observed in four of six patients on prolonged treatment. The responsiveness of Kaposi's sarcoma seen in this study in patients with low CD4 counts and prior constitutional symptoms (fever, weight loss) was unexpected and needs further confirmation by larger patient groups. Dose-limiting toxicities were bone marrow depression (severe anemia in four and neutropenia with anemia in two patients), subjective adverse experiences (fever, fatigue, myalgia; four patients) and both (two patients).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combined treatment with zidovudine and lymphoblast interferon-alpha in patients with HIV-related Kaposi's sarcoma. 190 99

This study was undertaken to define the maximum tolerated dose (MTD) of recombinant interleukin-2 (IL-2) that could be combined with a fixed dose of alpha-2a-interferon (alpha-IFN) in an outpatient setting. The schedule called for IL-2 to be given by a 2-hour intravenous infusion 5 days a week for 4 weeks. The alpha-IFN was given at a dose of 6 x 10(6) U/m2/d intramuscularly 3 days per week (Monday, Wednesday, and Friday). The IL-2 dose was escalated in four dose levels from 1 to 4 x 10(6) U/m2/d. The MTD in this study of 17 patients was at the fourth dose level of IL-2 (4 x 10(6) U/m2/d). In addition to the usual IL-2 toxicities, debilitating fatigue limited outpatient administration of this dose. Although the response rate was low, with partial responses seen in only 1 of 15 patients, 2 of 5 patients with melanoma treated at the higher dose levels had objective tumor shrinkage with one partial and one minor response. Thus, an IL-2 dose of 3 x 10(6) U/m2/d combined with a recombinant alpha-2a-IFN dose of 6 x 10(6) U/m2/d is recommended for Phase II studies.
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PMID:A phase I study of an outpatient regimen of recombinant human interleukin-2 and alpha-2a-interferon in patients with solid tumors. 191 12

In a pilot clinical trial, treatment of patients with advanced colorectal carcinoma with the combination of fluorouracil (5FU) and recombinant interferon alfa-2a (IFN) resulted in objective tumor regression in 62% of patients. To confirm these findings in a multiinstitutional setting, a phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) in 1989. The treatment regimen was identical to that used in the earlier study: 5FU 750 mg/m2/d for 5 days as a continuous infusion followed by weekly outpatient bolus therapy and IFN 9MU subcutaneously beginning day 1 and administered three times per week. Doses were modified for gastrointestinal, hematologic, and neurologic toxicity and for fatigue, similarly to those used in the previous pilot trial. Thirty-eight patients were registered; 36 are evaluable for response (one lost to follow-up and one with nonmeasurable disease). All patients had metastatic or locally recurrent disease beyond the scope of resection; 31 of 38 had liver metastases, and 20 of 38 had two or more sites of involvement. Eight patients had grade 4 toxicities, including sepsis (nonneutropenic) (one), watery diarrhea (two), and granulocytopenia (six). Grade 3 neurologic toxicities were observed in two (5%) patients and included slurred speech and gait disturbance. Objective response was 42% (95% confidence interval [Cl], 27% to 58%), including one clinical complete responder and 14 partial responders. Among the responding patients, the median time to treatment failure was 8 months. Two patients remain on treatment at 10+ and 16+ months: median survival has not been reached. The results of this multiinstitutional trial suggest that the addition of IFN to 5FU enhances the objective response rates achieved in patients with advanced colorectal carcinoma and that the toxicities of this regimen are acceptable.
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PMID:Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study. 191 31

In the present investigation, 20 patients with ET were treated with recombinant interferon alfa-2c (IFN) for up to 4 years. Initially, IFN was administered subcutaneously at a dosage of 6-45 MU/week. The dosage was adjusted according to individual tolerance and response. The median dose during induction was 20 MU/week, 10 MU/week during the remaining first year, 6 MU/week during the second year and 2 MU/week thereafter. 13 patients (65%) achieved complete remission (platelet count less than 440/nl), four patients (20%) had partial remission (greater than 440/nl but a reduction by more than 50% of the initial count). The median platelet count remained steady throughout the 4-year period of treatment, in spite of extreme dose reductions. After withdrawal of IFN, however, platelet counts again increased. The white blood cells showed a marked decrease similar to that of platelet counts, whereas the haemoglobin level remained fairly stable. In the bone marrow, a significant decrease in megakaryocyte density and size could be observed. Concurrently with the improvement of haematological parameters, clinical symptoms improved, but reappeared after withdrawal of IFN. During induction, fever, bone and/or muscle pain, fatigue, lethargy and psychological symptoms were the most prominent side-effects in the majority of patients. In three patients these symptoms led to discontinuation of the treatment. With repeated dose reductions, excellent long-term tolerance was achieved, and during late maintenance treatment the only observed side-effect was an induction of thyroid autoimmunity in three patients. IFN is an effective, well-tolerated alternative in the long-term treatment of symptomatic ET. However, since withdrawal of IFN leads to recurrence of thrombocytosis, continued treatment is to be recommended.
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PMID:Interferon in essential thrombocythaemia. 193 8


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