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)

A principal side effect of biological response modifiers (BRMs) is a constellation of constitutional symptoms often referred to as a "flu-like syndrome" (FLS). Precisely what this syndrome encompasses is frequently unclear, but its major components appear to be fever, chills, rigors, myalgias, and headache. Other components variously included are anorexia, nausea, upper respiratory symptoms such as nasal congestion and cough, and the ill-defined symptom, malaise. The manner in which the "flu-like" syndrome manifests itself during treatment with interferon (IFN), interleukin-2 (IL-2), tumor necrosis factor (TNF), monoclonal antibodies (MoAbs), and colony stimulating factors (CSFs) will be described with attention to frequency, duration and severity. The common mechanisms underlying the appearance of a flu-like syndrome during biotherapy will be elucidated with emphasis on the role of endogenous pyrogens and prostaglandins and on the physiology of the process. Methods to prevent or alleviate these uncomfortable side effects, including medical interventions such as alterations in schedule/route/dose of BRM administration and premedication with a variety of agents, as well as nursing measures such as patient education will be discussed.
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PMID:Recent advances in the management of biotherapy-related side effects: flu-like syndrome. 268 12

Twenty-seven patients with metastatic carcinoid tumor, 24 of whom had the malignant carcinoid syndrome, were treated with recombinant leukocyte A interferon at a planned dose of 24 x 10(6) U/m2. Twenty percent of patients with measurable tumor experienced an objective regression and 39% of those with the carcinoid syndrome experienced a reduction of more than 50% in urine 5-hydroxyindoleacetic acid (5HIAA) excretion. Flushing was partially or completely relieved in 65% of patients and diarrhea was relieved in 33%. Regrettably, these favorable treatment effects were transient in nature, with objective regressions persisting for a median of only 7 weeks and hormonal responses for a median of only 4 weeks. Any therapeutic gain experienced by these patients seemed to be outweighed by the frequency and severity of toxic reactions, which consisted primarily of chills and fever, fatigue, anorexia, weight loss, leukopenia, and abnormalities of liver function. Whereas other interferons, administration by alternative dosages and regimens, or incorporation of interferons into drug combinations may merit future study, we cannot recommend recombinant leukocyte A interferon, administered by the methods we employed, for routine therapy of the carcinoid tumor or syndrome.
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PMID:Therapy of metastatic carcinoid tumor and the malignant carcinoid syndrome with recombinant leukocyte A interferon. 273 23

In this phase I study 15 patients with metastatic tumors were given interferon (IFN)-beta by i.v. bolus injections. Twelve individual doses of 1, 2, 3.3, 5, 7, 9, 12, 16, 21, 27, 35, and 46 x 10(6) IU were administered every other day. The single maximal tolerated dose ranged from 9 to 46 x 10(6) IU. Eight patients tolerated the dose of 46 x 10(6) IU without side effects. Disturbances of cardiac rhythm were observed, but were closely related temporally to severe chills and appeared to be the consequence of adrenergic stimulation associated with this side-effect. In addition, no significant variations in the left ventricular function as assessed by nuclear stethoscope were observed. Neurotoxicity was not a major side-effect. The toxicity of IFN-beta given as scheduled in this study was significant, but acceptable.
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PMID:A phase I study of human natural interferon-beta in cancer patients. 274 22

Based on a preclinical study demonstrating the synergistic antitumor effect of recombinant interleukin 2 (rIL-2) and beta-interferon (IFN-beta) on mouse tumors and previous results of a phase I study of rIL-2, a phase I study of combination therapy with human rIL-2 and IFN-beta was conducted in 26 patients with advanced malignancy. Patients were given rIL-2 by 24-h continuous i.v. infusion and IFN-beta by 2-h i.v. infusion for 5 days each week for 4 weeks. The common side-effects were fever, malaise, chills, appetite loss, and diarrhea. Leukocytosis and eosinophilia were observed in 56% and 69% of the patients, respectively. Transient leukopenia and thrombocytopenia were also observed in some patients. Dose-limiting manifestations were intolerable fatigue and liver dysfunction, and it was concluded that the maximum tolerated doses of rIL-2 combined with IFN-beta were 1.1 x 10(6) U/m2/day for rIL-2 and 6.0 x 10(6) IU/m2/day for IFN-beta. No patients achieved complete and partial response to therapy in this study. One patient with pulmonary metastasis from pharyngeal cancer showed a minor response. Natural killer (NK) and lymphokine-activated killer (LAK) activities increased during the 5 days of treatment and decreased during the 2-day intermission. The percentage of IL-2 receptor-positive cells increased markedly until Day 12, and gradually decreased thereafter. The percentage of OKT 4-positive cells and the OKT 4/OKT 8 ratio increased. In contrast, the percentage of Leu 7- or Leu 11-positive cells decreased over the 4-week treatment. A phase II study of this combination therapy is ongoing against head and neck cancer, and renal cell carcinoma.
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PMID:Phase I study of combination therapy with interleukin 2 and beta-interferon in patients with advanced malignancy. 278 85

Because recombinant interleukin 2 (rIL-2) and recombinant alpha-interferon (rIFN-alpha) exhibit synergistic antitumor activity in C3HMT1820 T-cell lymphoma and B16 melanoma tumor systems, we have performed a Phase I study of this combination in 55 patients with advanced malignancies for whom no standard therapy exists. Successive groups of greater than or equal to 4 patients have been entered into 12 dose levels (1A-3D), with dose levels 1-3 referring to doses of rIL-2 of 0.1, 0.5, and 2.0 x 10(6) units/m2, respectively, and dose levels A-D referring to doses of recombinant human alpha 2a-interferon (rHuIFN-alpha 2a) of 0, 0.1, 1.0, and 10.0 x 10(6) units/m2. Both agents were given on Mondays, Wednesdays, and Fridays, with rIL-2 being given as i.v. bolus injections and rHuIFN-alpha 2a being given intramuscularly. Myelosuppression was dose-limiting and was related primarily to the dose of rHuIFN-alpha 2a. The maximum-tolerated dose level was reached at a dose of rIL-2 of 2.0 x 10(6) units/m2 and of rHuIFN-alpha 2a of 10.0 x 10(6) units/m2 (dose level 3D). At this dose level, 3/6 patients developed grade 3 neutropenia (absolute granulocyte count less than 1 x 10(9)/liter). Myelosuppression was transient, with no documented infections being associated with neutropenia. Hypotension was mild; a single patient was treated with a vasopressor, but all other cases of hypotension responded to fluid administration. No significant pulmonary toxicity was produced. Fever, chills, and malaise were universal but not dose-limiting. Three partial responses and one minor response were observed in patients with malignant melanoma, renal cell carcinoma, and breast cancer. Immunological studies suggested that natural killer activity was related to both the dose of rIL-2 and the dose of rHuIFN-alpha 2a, with natural killer activity being positively related to the dose of rIL-2 and maximal at the lowest dose of rHuIFN-alpha 2a of 0.1 x 10(6) units/m2.
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PMID:Phase I clinical trial of interleukin 2 and alpha-interferon: toxicity and immunologic effects. 280 86

Eighteen patients with advanced non-small-cell lung cancer (NSCLC) received recombinant beta interferon, 90 million units three times weekly. No complete or partial responses were seen. Five patients had stable disease for several months. Most patients experienced some toxicity, most commonly fever and chills. No dose reduction of interferon had to be made due to toxicity. Tachyphylaxis to symptoms of fever and chills occurred in most patients. While 33% of patients developed beta-interferon-binding antibodies, the incidence of interferon-neutralizing activity was 0%. This dose and schedule of beta interferon did not result in significant anti-tumor effects in advanced NSCLC. Stabilization of disease for up to 9 months in patients with previously progressive disease was of interest. Tachyphylaxis of symptoms should allow for dose escalation within patients. A dose-escalating study has been initiated to evaluate the efficacy of beta interferon when given at each patient's maximally tolerated dose.
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PMID:Phase II study of recombinant beta interferon in patients with advanced non-small-cell lung carcinoma. 282 2

Sixteen patients with cervical intraepithelial neoplasia (CIN), grades 2 and 3, and vulvar intraepithelial neoplasia (VIN), grade 3, associated with human papillomavirus (HPV) infection were treated with human fibroblast interferon (HFI). Treatment consisted of 2-3 X 10(6) IU/day injected intra- and perilesionally for five days per week for two to three weeks with or without topically applied cream (1.2 X 10(6) IU/day for five days). Eight complete and two partial regressions occurred. The duration of the response ranged from 4 to 20 months. Fever, chills and fatigue with or without headache were the side effects. Our preliminary results indicate that HFI was active against CIN and VIN associated with HPV infection.
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PMID:Human fibroblast interferon in cervical and vulvar intraepithelial neoplasia associated with viral cytopathic effects. A pilot study. 298 15

Fifteen patients with advanced malignancy were treated with recombinant interferon gamma (rIFN-gamma) (specific activity approximately 2 X 10(7) units/mg, purity greater than 99%) given by 1-hour iv infusion three times a week for 6 weeks, at fixed dose levels of 0.1, 0.5, 1.0, or 2.0 mg/m2/day. The common side effects were constitutional symptoms, including fever, chills, myalgias, and headache, but these were less severe than those observed following daily 6-hour iv infusions. Significant changes in blood cell counts and routine serum chemistries were not observed, but there was a dose-dependent increase in serum triglyceride levels. The maximum safely tolerated dose achieved was 1.0 mg/m2/day. Peak serum interferon levels occurred at the midpoint of the infusion and were dose-dependent. rIFN-gamma was rapidly cleared from serum and no detectable activity was found 2 hours after the infusion. Two patients, both with B-cell malignancies, showed objective evidence of tumor regression during the treatment. Treatment was associated with an increase in serum levels of beta 2-microglobulin and the H2O2 secretory capacity of peripheral blood monocytes. We conclude that rIFN-gamma administered by short iv infusion can induce biological activities and causes less toxicity than when given by prolonged iv infusion.
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PMID:Phase I trial of recombinant interferon gamma by 1-hour i.v. infusion. 308 30

Recombinant human gamma interferon (Biogen) and vinblastine were administered in a phase I study. Side effects included fever and chills, nausea and vomiting, acute symptomatic hyponatremia, reversible myelosuppression, hepatitis, transient hypotension, congestive heart failure, renal insufficiency, and nonselective proteinuria. In most patients, additional host factors contributed to these toxic effects. Side effects occurred despite dose reduction; therefore, protocol accrual was prematurely closed. No correlation between serum concentrations and toxicity was noted. Median serum vinblastine concentration was 1.04 ng/ml; median serum interferon concentration was 17.3 IU/ml.
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PMID:Hyponatremia and other toxic effects during a phase I trial of recombinant human gamma interferon and vinblastine. 309 Dec 46

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


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