Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085593 (chills)
4,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant interferon alfa-2a (Roferon-A, Hoffmann-La Roche Inc., Nutley, NJ) has been evaluated in clinical trials of more than 1300 patients with a broad spectrum of oncologic disease. Patients with either solid tumors or hematologic malignancies were treated with daily or three-times-weekly intramuscular injections for induction periods ranging from 8 to 16 weeks. Doses ranged from 1 X 10(6) units to 124 X 10(6) units per injection. When administered in low daily doses (approximately 3 X 10(6) units), Roferon-A was well tolerated, and dose attenuation was rarely required. Change to three-times-weekly treatment regimen at the same dose was usually sufficient to control toxicity when it occurred in this group of low-dose patients. Those patients receiving higher doses frequently required dose attenuation to 50% of the starting dose to improve clinical tolerance. Virtually all patients treated with Roferon-A experienced some degree of acute toxicity manifested as fever, chills, myalgia, and/or headache. These reactions usually occurred with initial dosing and frequently improved spontaneously with continued administration of the drug. Acetaminophen pretreatment was generally useful in ameliorating these symptoms. Common adverse experiences occurring after repeated dosing included fatigue, anorexia, and weight loss. Serious adverse reactions including cardiovascular and neurologic toxicity have occurred infrequently, primarily at higher doses. Hematologic toxicity and elevations in liver function parameters were also observed, but rarely required dose attenuation. Adverse effects were usually reversible after dose reduction or discontinuation of therapy. Approximately 27% of all patients developed antibodies to rHuIFN-alpha 2A during treatment. No adverse clinical sequelae have been associated with antibody development to date.
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PMID:Safety and tolerance of recombinant interferon alfa-2a (Roferon-A) in cancer patients. 394 43

Ten patients with advanced cancer were treated with weekly intravenous escalating doses of human beta-interferon (HuIFN beta) 4 days each week. The starting dose of HuIFN beta was 3.0 X 10(6) units/m2 and the dose was doubled each week until dose-limiting toxicity was observed. Subjective toxicity included mild fevers and chills, malaise and flu-like symptoms. The lowest dose which caused suppression of the platelet and/or white cell count was 64 X 10(6) units daily, and the maximum dose given was 320 X 10(6) units daily. Both subjective and objective toxicity were not dose-related, easily managed and reversible. Serum interferon levels and the duration of measurable interferon activity on natural killer cells was in general dose-dependent. Two patients had an objective partial response, and two others showed stable disease while receiving HuIFN beta.
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PMID:Extended phase I study of human beta-interferon in human cancer. 395 19

Because two of five patients with renal cell carcinoma in a Phase I study had partial response to recombinant alpha-2 interferon (IFN), we treated 26 patients with advanced renal cell carcinoma with a 3-month regimen of IFN. Patients were randomized to receive IFN either subcutaneously (2 X 10(6) IU/m2 3 times a week) or intravenously (3 X 10(7) IU/m2 for 5 consecutive days every 2-3 weeks). Patients whose disease was responding or stable were treated further, while those with progressive disease on subcutaneous treatment were offered intravenous therapy. Sites of metastasis included lung (14 patients), bone (7 patients), soft tissue (7 patients) and liver (2 patients). Twenty patients were evaluable for response. One patient had a partial response at the end of the third course of intravenous IFN and subsequently had complete disappearance of a 12 X 7 cm subcutaneous mass after the seventh course of treatment. The disease was stable in 13 patients including two minor responses, and six patients had progressive disease (5 with subcutaneous treatment; 1 with intravenous treatment) including one mixed response. All patients experienced early flu-like symptoms of fever, chills, and rigors during the first few days of treatment and most had mild to moderate fatigue. Three patients left the study because of fatigue, and one had an urticarial rash. From these results and our previous experience, it appears that IFN has activity against renal cell carcinoma with acceptable toxicity.
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PMID:Recombinant interferon alpha-2 (INTRON A) in a phase II study of renal cell carcinoma. 395 53

Recombinant leukocyte A interferon is a highly purified single molecular species of alpha-interferon prepared by recombinant DNA methods. In 1982, a phase II trial to evaluate the efficacy of recombinant leukocyte A interferon for patients with previously treated chronic lymphocytic leukemia was begun, and 19 patients were entered in this study. Patients received one of two dose schedules depending on their pretreatment platelet counts. Those with platelet counts greater than 100,000/mm3 received 50 X 10(6) units/m2 intramuscularly three times weekly, with dose reductions to 25 X 10(6) units/m2 and 5 X 10(6) units/m2 for unacceptable toxicity. Those with platelet counts less than 100,000/mm3 received 5 X 10(6) units/m2 intramuscularly three times weekly. Toxicity was dose-dependent and included fever, chills, fatigue, anorexia, myalgias, headache, leukopenia, and thrombocytopenia. Response was evaluable in all but one of the patients entered in this study. Two of the 12 patients treated with 50 X 10(6) units/m2 had a partial response, three had no response, and seven had progressive disease. Of the six patients starting at 5 X 10(6) units/m2 in whom response was evaluable, two had no response and four had progressive disease. Five patients with progressive disease (three at 50 X 10(6) units/m2 and two at 5 X 10(6) units/m2) had an acceleration of disease while receiving recombinant leukocyte A interferon. It is concluded that the dose and schedule of recombinant leukocyte A interferon therapy tested in this study are not effective in previously treated patients with advanced chronic lymphocytic leukemia.
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PMID:Phase II trial of recombinant leukocyte A interferon in patients with advanced chronic lymphocytic leukemia. 397 47

Twenty-two patients with measurable metastatic renal carcinoma were treated with human alpha lymphoblastoid interferon (Wellferon) (3 million units/m2 of body surface area) im three times a week for 6 weeks; 21 were evaluable for response and toxicity. One patient had a partial regression of disease lasting 39 weeks and another had a minor response. Six patients had partial or minor response in one area but no change in the disease elsewhere (mixed response); they were classified as having stable disease. An additional seven patients had no change in measurable disease and in six the disease progressed. The tumor regressions by metastatic site were four of 14 patients, pulmonary; three of four, soft tissue; one of nine, bone (? soft tissue); none of three, mediastinal; none of four, renal; none of five, liver; and none of ten, other abdominal sites of tumor. The side effects were fever (101 degrees F-103 degrees F), chills, malaise, anorexia, minor (10%-20%) decrease in performance status, and weight loss. We concluded that interferon had some activity against metastatic renal carcinoma, although clinically useful responses were quite infrequent. While lung metastases appeared to be more responsive than those at other sites, careful examination of the data suggests that this simply reflects differences in the bulk of the metastatic disease. Smaller metastases appear more likely to respond than bulky metastases.
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PMID:Phase II study of human lymphoblastoid interferon in patients with advanced renal carcinoma. 401 92

Human alpha lymphoblastoid interferon (Wellferon) was administered to 33 patients in a phase I study. Patients received Wellferon intramuscularly every 12 hours for 14 doses in nine dosage levels ranging from 0.75 X 10(6) units to 50.0 X 10(6) units. Toxicity tended to be dose dependent and included fever/chills, malaise, hematologic toxicity, and digestive tract toxicity. Thirty X 10(6) u q 12 h was felt to be the maximum tolerated dose. Three partial responses (renal cell carcinoma, diffuse histiocytic lymphoma, Hodgkin's disease) were achieved. Interferon rapidly (2 to 3 hours after the initial injection) reached peak serum levels which varied generally with dose and exceeded 500 u/ml at the 30 and 50 X 10(6) u dosages. Multiple doses of interferon resulted in cumulative peak levels substantially higher than first dose levels (greater than 500 u/ml at dosages greater than 3 X 10(6) u/ml and greater than 1,500 u/ml at dosages greater than or equal to 18 X 10(6) u). Interferon given at high dosages persisted up to 10 days beyond the final injection. Despite hematologic toxicity, inhibition of CFU-GM was not seen.
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PMID:Human alpha-lymphoblastoid interferon. A phase I study including pharmacokinetics and effects on hematologic stem cells (CFU-GMs). 406 75

The follow-up is presented for 13 patients with cervical intraepithelial neoplasia (CIN) grade II-III and vulvar intraepithelial neoplasia (VIN) grade III associated with papilloma virus infection, treated with human fibroblast interferon. Treatment consisted of 2-3 X 10(6) IU interferon per day injected intra- and peri-lesionally for five days per week for 2-3 weeks, with or without a cream topically applied at the dose of 1.2 X 10(6) IU/day X five days. Among the 13 patients with CIN and VIN, 7 complete (54%) and 2 partial regressions were observed. The duration of response appeared to be between 2 and 14 months. Fever, chills and fatigue were the tolerable side-effects. Our results indicate that treatment with interferon is active against CIN and VIN associated with papilloma virus infection.
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PMID:Human fibroblast interferon in cervical and vulvar intraepithelial neoplasia associated with papilloma virus infection. 609 44

Sixteen patients with advanced cancer were treated with recombinant-DNA-produced pure leukocyte A interferon (IFLrA) intramuscularly in doses ranging from 3 to 198 X 10(6) units. with interval periods of 72 to 96 hours between doses. At the two lowest doses of 3 and 9 million units, there was a cross-over evaluation between IFLrA and partially pure leukocyte interferon (IFN-C) produced from human cells. THe maximum observed serum concentration of IFLrA measured by enzyme immunoassay and bioassay increased with increasing doses. The mean serum concentrations of IFLrA and IFN-C were similar. Clinical effects produced by IFLrA and IFN-C were similar, including fever, chills, myalgias, headache fatigue, and reversible leukopenia and granulocytopenia. Eight patients had transient and mild numbness of the hands or feet, or both. Three patients developed low titers of antibody to IFLrA, Seven of 16 patients showed objective evidence of tumor regression during the study.
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PMID:Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients. 617 59

6 patients with amyotrophic lateral sclerosis were treated with intravenous infusion of 100-200 million IU per day of human leukocyte interferon. Side effects of treatment included fever, chills, malaise, nausea, marked leukopenia, mild anemia, and thrombocytopenia. Tiredness, confusion, papilledema, and overall signs of acute encephalitis were observed. Tendon reflexes and muscle force decreased. EEG activity was slowed, and evoked potentials showed significant slowing of conduction times. Neuropsychological tests revealed congitive dysfunction. The syndrome of inappropriate antidiuretic hormone secretion developed in all patients. All side effects were reversible with cessation of interferon treatment.
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PMID:Neurotoxic and other side effects of high-dose interferon in amyotrophic lateral sclerosis. 620 81

The induction of endogenous interferon (IFN) was studied in 28 cases of Argentine hemorrhagic fever (AHF), a severe systemic disease caused by Junin virus. Serum samples were taken daily during the acute period, both before and after administration of immune plasma. This form of treatment has been found to reduce mortality when given early in the course of AHF. High titers of circulating IFN were present in the serum samples taken before treatment. IFN titers drastically dropped after transfusion of immune plasma. The antiviral activity was stable at pH 2 and was completely neutralized only by antibodies against IFN-alpha. Thus, we concluded that circulating endogenous IFN in patients with AHF can be considered as typical IFN-alpha. Fever, chills, and backache were associated with the higher levels of IFN. An inverse correlation between days of evolution of the disease and IFN activity was also observed.
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PMID:Endogenous interferon in Argentine hemorrhagic fever. 623 26


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