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 prospective phase I clinical trial with recombinant interferon-alpha-2b as maintenance therapy after cytotoxic chemotherapy was conducted. Twenty-one homosexual and bisexual males with extensive mucocutaneous or visceral epidemic acquired immunodeficiency syndrome (AIDS)-Kaposi's sarcoma (KS) were studied. After a complete response (6 patients) or partial response (15 patients) from chemotherapy consisting of Adriamycin (20 mg/m2), bleomycin (10 U/m2), and vincristine (1.4 mg/m2; 2 mg maximum), patients were given interferon-alpha (IFN-alpha) in an attempt to prolong disease-free survival. Three dose levels of daily IFN-alpha were tested: 5, 10, and 15 million U. The maximum tolerated dose was 10 million units. Dose-limiting toxicities included recurrent grade 3 fatigue, diarrhea, and fever, which resulted in the termination of therapy in eight patients (38%). Hematologic toxicities were infrequent (four patients; 19%). Responses were observed in two patients on IFN-alpha, both at the 10-million-U dose level. The median duration of response on IFN-alpha therapy following chemotherapy was 8 weeks (range, 3-11). We conclude that the duration of IFN-alpha maintenance response following cytotoxic chemotherapy is short with response to residual disease observed in a minority of cases at this dose and schedule. Additional trials of maintenance therapy in patients with advanced AIDS-KS combining antiretroviral agents are in progress.
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PMID:Interferon-alpha maintenance therapy after cytotoxic chemotherapy for treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma. 225 62

Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma.
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PMID:Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma. 233 72

Human lymphoblastoid interferon (IFN-alpha MOR-22; OIF) was administered to forty-two patients suffering from renal cell carcinoma. Twenty-six patients with metastatic lesions or primary tumor were treated in a clinical trial with either MOR-22 alone or combination of MOR-22 and UFT (or FT-207). The efficacy was assessed in ten of twenty patients who had received MOR-22 alone for more than eight weeks, but objective response was not observed. The efficacy was done in eight of fourteen patients with MOR-22 and UFT (or FT-207) in combination. Complete response was achieved in one, and partial response in two, with an objective response rate of 37.5%. But the difference was no statistically significant in the survival rate of each therapy. In evaluable twenty patients with MOR-22 prophylactically, there was only one case who had occurred lung metastases with a refractory rate of 8.3%. Forty-one patients were examined for side effects to drugs. The main side effects were fever, anorexia, general fatigue, hematologic toxicities, and hepatic dysfunction in both therapy. These side effects occurred with more increased frequency in combination therapy of UFT (or FT-207) compared to MOR-22 alone.
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PMID:[Combination therapy of renal cell carcinoma with interferon-alpha and UFT (or FT-207)]. 250 5

Fifteen patients with metastatic malignant melanoma, including 10 who had not previously received systemic therapy, were treated with recombinant alpha2-interferon (IFN-alpha 2) in a dose of 20 million IU/m2 by 30-min i.v. infusion daily for 5 days each 14 days. Evaluable metastatic sites included lung, subcutaneous tissue, liver, nodes, adrenals, and bone. Subjective toxicity was generally mild to moderate, with fever (38.2-40.2 degrees C), occasional rigors, fatigue, myalgia, headache, and nausea. Objective toxicity included transient neutropenia and elevation of hepatic enzymes, particularly gamma-glutamyl transpeptidase. In 1 of the 10 patients receiving more than one cycle, IFN dosage was reduced because of toxicity, but later reescalated. All patients were evaluated for response. No overall partial or complete responses were observed, but two site responses (lung and subcutaneous tissue) were seen. Median survival from start of IFN treatment was 19 weeks. High doses of IFN were reasonably well tolerated in this study, but the results suggest little activity against malignant melanoma.
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PMID:Phase-II study of recombinant alpha 2-interferon in advanced malignant melanoma. 287 Nov 16

Human leukocyte interferon, HuIFN-alpha (LE), has been tested in combination with radiotherapy and chemotherapy for previously untreated small cell lung cancer. Nine patients with limited disease received high-dose IFN followed by a low-dose regimen; and six patients had a low-dose regimen from the beginning. The high dosage of IFN consisted of 800 X 10(6) IU given as a continuous intravenous infusion for 5 days, followed by 6 X 10(6) IU i.m. three times weekly. If the first site of disease progression was local or in a central nervous system location, radiotherapy (55 Gy/20 F/7 weeks locally and/or 30 Gy/10 F/2 weeks whole brain) was applied and IFN was continued. Chemotherapy was administered only if there was disease dissemination outside the chest. Three patients achieved minor response for as long as 20, 25, and 42 weeks, respectively, with IFN alone. Three of five complete responders to IFN-radiotherapy died 18, 33, and 41 weeks from the start of IFN treatment without chemotherapy. Autopsy did not reveal macroscopic or microscopic tumor at any site, but there was severe radiation pneumonitis. Four of nine patients were administered chemotherapy subsequent to IFN-radiotherapy because of disease dissemination. The median length of survival of the entire group was 41 weeks. On the low-dose regimen, one patient achieved partial response with IFN alone (duration, 12 weeks); of five evaluable patients three achieved complete remission and two partial remission to IFN-radiotherapy, and one of the three complete responders to IFN-radiotherapy died of severe radiation pneumonitis at 21 weeks from the start of IFN treatment. No tumor was detected at autopsy. The study is in progress. Average survival at present is 33 weeks. The results derived from both our studies suggest a growth-delaying effect of HuIFN-alpha (Le) on small cell lung cancer. They also suggest potentiation of radiation by HuIFN-alpha (Le). Memory and psychomotor dysfunction, fatigue, and anorexia were dose limiting with both short-duration, high-dose and long-duration, low-dose IFN therapy. We feel that IFN, as part of a combined multimodality treatment of small cell lung cancer, may play a role by delaying metastatic dissemination.
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PMID:Human leukocyte interferon as part of a combined treatment for previously untreated small cell lung cancer. 298 40

A 59-year-old male was admitted to our hospital with complaints of general fatigue, abdominal distension and edema in the legs in February, 1985. Laboratory findings were as follows: GOT 152 IU/l, GPT 129 IU/l, LDH 555 IU/l, ALP 1147 IU/l, gamma-GTP 413 IU/l, T.-Bil 2.1 mg/dl and AFP 422.6 ng/ml. Multiple SOLs were recognized in both lobes of the liver by abdominal CT scan and echography. Interferon-gamma (gamma-IFN: KW-2202; Kyowa Hakko Co.) therapy was started in March from an initial dose of 1 X 10(6) units and was increased up to 4 X 10(6) units, 2 X 10(6) units being administered as a maintenance therapy for 12 weeks. The tumors became remarkably smaller in size, AFP was decreased to 38.8 ng/ml, and PR was obtained. The only side effect was temporary fever. The patient was subsequently followed without gamma-IFN at an outpatient clinic for about 100 days, but finally died due to rupture of esophageal varices and hepatic failure.
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PMID:[A case of hepatoma with a remarkable response to gamma-interferon administration]. 301 53

Interferon gamma (IFN-gamma) is a lymphokine with potent in vitro effects on cell growth and immune function. We have investigated the effects of rIFN-gamma (sp act approximately 2 X 10(7) U/mg, purity greater than 99%) in 16 evaluable patients with advanced malignancy in a phase 1 trial. Patients were treated with six-hour intravenous (IV) infusions daily, five days a week for 2 weeks. After a 2-week rest period, the IV treatment cycle was repeated. Responders were maintained on repeated IV treatment cycles or daily intramuscular (IM) injections. Patients were entered at fixed dose levels of 0.1, 0.5, or 1.0 mg/m2/d. The maximum safely tolerated dose was 0.5 mg/m2. The most common side effects were constitutional symptoms, including fever, chills, fatigue, and myalgias. Reversible and transient increases in hepatic transaminase and decrease in granulocyte counts were seen. Treatment was associated with a dose-dependent increase in serum levels of beta 2 microglobulin. Partial responses (PRs) were observed in one patient with Hodgkin's disease and one patient with chronic lymphocytic leukemia. Fairly constant levels of serum IFN were found at four and six hours during infusion, followed by a rapid decline within one to two hours. We conclude that rIFN-gamma can be safely administered by a six-hour IV infusion and that it can induce in vivo some of the biologic effects reported in in vitro studies.
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PMID:Phase I trial of recombinant interferon gamma in cancer patients. 308 May 51

Combinations of interferon-alpha and interferon-gamma demonstrate synergistic antiviral and anti-proliferative activity in vitro. Therefore, we initiated a clinical study of combination interferon therapy in humans. Eighteen patients with metastatic solid tumors received daily intramuscular (IM) injections of recombinant interferon-alpha-A (IFN alfa-2a, Roferon-A; Hoffman-LaRoche, Nutley, NJ) and recombinant IFN-gamma (rIFN-gamma) for 6 weeks. The dose levels were 0.5, 1.0, 2.0, and 5.0 X 10(6) U/m2/d of each interferon. A minimum of two patients were entered sequentially at each dose level. Fever, chills, fatigue, and a greater than or equal to 50% drop in granulocyte counts were observed at all doses. Severity of symptoms corresponded to increasing dose levels. In contrast to the tachyphylaxis to these symptoms that usually develops in patients treated with the individual interferons, many patients on this study experienced persistent fever and worsening fatigue over 6 weeks. The maximum tolerated dose was 1 X 10(6) U/m2/d of each interferon. One patient with renal-cell carcinoma achieved a partial remission (duration, 3 months). Enzyme-linked immunoassay analysis in all four patients for whom complete data were available revealed that peak blood levels of IFN alfa-2a on day 22 were about tenfold higher than on day 1. Because of the possibility of cumulative toxicity, the recommended starting dose for further studies is 0.5 X 10(6) U/m2/d of each interferon, with escalation to 1.0 X 10(6) U/m2/d after 1 month if tolerance is acceptable. Phase II investigations to explore the antitumor efficacy of this regimen are planned.
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PMID:Phase I study of a combination of recombinant interferon-alpha and recombinant interferon-gamma in cancer patients. 309 4

Gamma-interferon appears to be a pivotal molecule in the immune system. Recombinant DNA technology has permitted the cloning and expression of the gene for gamma-interferon (gamma-IFN), leading to an exponential increase in the level of knowledge both in vitro and in vivo. Laboratory evidence suggests a clinical role for gamma-IFN in collagen vascular disease, chronic granulomatous infectious diseases, hematology, and medical oncology. Phase I trials have identified the toxicities; these toxicities are primarily clinical and include fever, fatigue, flu-like symptoms, and hypotension. Antitumor activity has been noted in the early development of the drug.
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PMID:Gamma-interferon: physiology and speculation on its role in medicine. 311 Mar 78

Six patients with hairy-cell leukemia were treated with gamma-(IFN-gamma) and alpha-(IFN-alpha-2b) interferon; 3-35 months following splenectomy, treatment was started with 4 X 10(6) U/m2 IFN-gamma sc (iv) every second day for 9-35 weeks. Although the white blood cell counts decreased during therapy from 4.1-49 X 10(9)/l to 1.5-43 X 10(9)/l, no hematological or clinical improvement was obtained. Subsequently (interval 0-13 weeks), IFN-alpha-2b was given at an initial dose of 4 X 10(6) U/m2 sc every second day to all patients. After a treatment period corresponding to that of IFN-gamma administration, a significant hematological improvement was observed in five patients (one early death due to pulmonary embolism). At the last follow-up (9-14 months after start of treatment; maintenance therapy, 1 X 10(6) U every second day), these patients exhibited normal peripheral blood cell counts, and in bone marrow biopsy specimens a marked decrease of hairy cells was seen (1 CR, 3 PR, 1 MR). Adverse reactions including fever, headache, nausea, dryness of the mouth, myalgia, and fatigue did not significantly differ between the two interferon preparations. Whereas IFN-gamma is unlikely to have any significant impact on the course of hairy cell leukemia, IFN-alpha-2b does result in improvement of hematological values and well-being in almost all patients.
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PMID:[Effectiveness of gamma interferon and alpha interferon in hairy cell leukemia]. 311 51


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