Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel approach to adoptive immunotherapy is described in this study. Of 13 patients with malignant effusions, nine were treated by intraperitoneal (IP) instillation of intracavitary lymphocytes (ICL), activated ex vivo by recombinant interleukin-2 (rIL-2, Cetus Co., Emeryville, CA) with escalating doses of IP rIL-2 and four by IP rIL-2 alone. ICL and rIL-2 were administered by repeated peritoneal punctures. Patients were divided into two groups: group I of six patients, who received activated ICL with low doses of IP rIL-2 (total dose not exceeding 6 X 10(5) units) and group II of seven patients, in whom escalating higher doses of rIL-2 were administered IP with or without activated ICL, in doses ranging from 10(6) up to 16 X 10(6) units, total dose. Total dose of ICL given ranged from 2 X 10(8) to 2 X 10(9) in both groups. The main objectives of this pilot study was to establish the feasibility of treatment by ex vivo activated ICL and IP rIL-2, to assess the toxicity associated with such a treatment, to escalate doses of rIL-2 to a maximal tolerable dose, and to look for clinical responses. The first two goals were achieved: such a treatment approach is feasible and is not associated with severe toxicity. The side effects observed during this study were usually mild in group I patients and more pronounced in group II patients. These included transient fever, chills, nausea, cellulitis at the puncture site, and one case of peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A pilot study of intraperitoneal recombinant interleukin-2 and ex vivo activated intracavitary lymphocytes in patients with malignant peritoneal spread: I. Clinical aspects. 260 15

The purposes of this work are to: review the biological activities of Interleukin-2 (IL-2); evaluate the reported therapeutic benefits and toxicity of IL-2/lymphokine activated killer (LAK) cells; and project the role of IL-2/LAK cells in cancer therapy. Interleukin-2 is a glycoprotein lymphokine (mw 15,000) produced naturally by mitogen or antigen stimulated T-lymphocytes. The activities of IL-2 include: enhancement of IL-2 receptor positive T-lymphocytes and a variety of other in vitro and in vivo alterations of T cell function. The IL-2 gene has been cloned from the Jurkat leukemia cell line and expressed by recombinant biotechnology in an E. coli vector. In vitro incubation of IL-2 with selected T-lymphocytes results in the formation of lymphocyte activated killer (LAK) cells. Rosenberg and colleagues, in 1983, demonstrated that both exogenous IL-2 and LAK cells were needed in order to get maximum tumor regression in a murine model and later humans. Patients selected for IL-2/LAK cell therapy have clinical metastases or advanced unresectable cancers. Almost all patients treated demonstrate some toxic effects, including chills, fever, nausea, vomiting, diarrhea and hepatic dysfunction. Approximately 75 percent of the patients have profound hypotension and require intensive nursing care. A review of the literature indicates that tumor responsiveness will range from negligible (adenocarcinoma of the lung with metastases) to a 30+ percent response in renal cell carcinoma when complete and partial responders are totalled. Interleukin-2/LAK cell therapy has promise for some wide spread tumors for which no other therapy is available.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-2 and lymphokine activated killer cells: promises and cautions. 264 90

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

High-dose interleukin-2 (IL-2) with or without lymphokine-activated killer (LAK) cells has been reported to have activity in certain solid tumors, but toxicity has usually required hospitalization for administration. The purpose of this trial was to determine the antineoplastic effect and toxicity of IL-2 administered at a lower dose in an outpatient setting. Eligibility criteria included measurable disease, Karnofsky performance greater than or equal to 70%, age greater than 18 years, and adequate bone marrow, renal, and hepatic function. The median age of 35 patients was 56 years (range, 20 to 75). Diagnoses included malignant lymphoma (ML), (nine patients), chronic lymphocytic leukemia (CLL) (eight), melanoma (eight), colorectal cancer (six), renal cancer (two), and breast cancer (two). The initial 18 patients were treated with 1 mg/m2 (3 x 10(6) U/m2 intravenous [IV] bolus) for five days every other week for a total of 4 treatment weeks (8 weeks total). The subsequent 17 patients were treated with 0.5 mg/m2 (1.5 x 10(6) U/m2). All patients were evaluable for toxicity, and 26 for tumor response. Toxicities included fatigue (71%), nausea (69%), hypotension (54%), fever (51%), chills (40%), weight gain (37%), pruritus or rash (31%), dyspnea (14%), azotemia (6%), confusion (6%), thrombocytopenia (6%), and myocardial infarction (3%). Four patients died from apparently unrelated causes within the first 2 weeks of treatment. Treatment was discontinued before the completion of 8 weeks of treatment because of progressive disease (12 patients), severe hypotension (three), azotemia (one), myocardial infarction (one), early death (four), and miscellaneous causes (two). IL-2 at 1 mg/m2 IV for five days is associated with moderate toxicity, but a dose of 0.5 mg/m2 is tolerable for outpatient administration. Three partial responses (PR) and one minor response (MR) lasting 1 to 17+ months have been observed in 12 patients with ML and CLL evaluable for response. One additional MR was observed in a patient with melanoma. IL-2 deserves further study in patients with ML and CLL.
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PMID:Phase II trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia, and selected solid tumors. 278 39

Recombinant interleukin-2 (rIL-2) (NSC# 600664; Hoffmann-La Roche, Inc., Nutley, NJ) was studied in a phase I clinical trial in 33 patients with advanced, measureable cancer of the colon or malignant melanoma, Eastern Cooperative Oncology Group (ECOG) performance status O-1, and no prior chemotherapy or radiotherapy. The goal of the study was to identify a dose and schedule of IL-2 to generate maximal immune modulation with tolerable toxicity. Such a regimen might allow the addition of other treatment modalities and/or prolonged treatment duration in later trials. Each patient received IL-2 as a continuous 24-hour infusion once weekly for 4 weeks and then twice weekly for 4 weeks. Five treatment groups received from 10(3) U/m2 to 3 x 10(7) U/m2 per 24-hour infusion. The maximal tolerated dose was 3 x 10(7) U/m2/d twice weekly. Patients treated twice weekly at 1 x 10(7) and 3 x 10(7) U/m2/d had immune modulation in terms of lymphocytosis, eosinophilia, increased natural killer (NK) activity, and elevated numbers of peripheral blood mononuclear cells expressing CD16, OKT10/Leu-17, and Leu-19 surface markers. Endogenous generation of peripheral blood lymphokine-activated killer (LAK) activity was demonstrated by lysis of NK-resistant Daudi targets, in patients treated at 3 x 10(7) U/m2/d. Biochemical and hematological abnormalities were moderate and reversible. Clinical toxicity included hypotension, myalgia, arthralgia, stomatitis, fever, fatigue, nausea, headache, chills, diarrhea, and oliguria at high doses. Cardiovascular toxicity was tolerable for most patients and reversed after IL-2 was stopped. Two of six melanoma patients at 3 x 10(7) U/m2/d achieved partial responses by the end of the eighth week. This IL-2 schedule appears to produce potentially clinically useful immune enhancement with tolerable toxicity.
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PMID:A phase I clinical trial of recombinant interleukin-2 by periodic 24-hour intravenous infusions. 278 32

Nineteen evaluable patients with advanced malignancy were treated with recombinant methionyl human interleukin-2 (Ala 125), 5 days per week by intravenous bolus. Patients were entered in five groups at starting doses ranging from 0.05 to 2.56 x 10(6) U/m2. Doses were escalated weekly as tolerated toward a potential maximal dose of 11.6 x 10(6) U/m2. Maximal tolerated dose was 3.84 x 10(6) U/m2. Dose-limiting toxicity included fatigue, rigors, nausea/vomiting, fever, and diarrhea. Other toxicities included hyperesthesias, arthralgias/myalgias, rash, fluid retention, balanitis, and mild confusion. Leukocytosis, including granulocytosis, eosinophilia, and mild lymphocytosis, was observed, as was rare mild thrombocytopenia. No partial or complete response occurred. T1/2 alpha averaged 13.4 min, with interleukin-2 detectable 2 h after doses of greater than or equal to 2.56 x 10(6) U/m2. Three patients developed anti-IL-2 antibodies without demonstrable clinical significance.
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PMID:Systemic administration of recombinant methionyl human interleukin-2 (Ala 125) to cancer patients: clinical results. 278 63

Interleukin-2 (IL-2) and beta-interferon (beta-IFN) are cytokines with profound immunobiological effects on T-cell and natural killer (NK) cell activity; IL-2 also induces lymphokine-activated killer (LAK) cell cytotoxicity in humans. Both lymphokines induce antineoplastic activity against several refractory tumors. This Phase I study of 50 patients assessed the toxicities, maximally tolerated dose (MTD), effects on certain immune effector cells, pharmacokinetics of IL-2, and development of antibodies to the combination of subcutaneously administered IL-2 and intravenously administered beta-IFN. Fever was common. Indomethacin reduced the incidence and severity of fever and was necessary to prevent it from becoming dose-limiting. Hypotension occurred but never required pressors or produced complications. Constitutional symptoms, local skin toxicity at the site of IL-2 injection, generalized desquamation, eosinophilia, nausea, and vomiting were also observed. One patient had reversible renal dysfunction. Two patients experienced drug-related dyspnea without evidence of capillary leak syndrome; neither required intubation. Fluid retention and cardiotoxicity were not observed. The MTD was 5 x 10(6) U/m2 s.c. of IL-2 and 2 x 10(6) U/m2 i.v. of beta-IFN when given in combination. Enhancement of in vivo NK cell cytotoxicity and proliferation of T4+, T8+, and NK cells occurred. In vivo induction of LAK cell cytotoxicity was observed in three patients. Four patients developed nonneutralizing anti-IL-2 IgG antibodies, but none developed antibodies to beta-IFN. Peak IL-2 serum levels typically occurred 4 h following drug administration. Serum levels were within a factor of 3 of the peak level in the period studied, 1-6 h postinjection. No complete responses occurred. One patient with rectal cancer and one with transitional cell carcinoma each had a partial response, and 13 other patients (5 with renal cell, 4 with colorectal, and 4 other cancers) had stable disease. Induction of NK cell cytotoxicity was seen more commonly in patients with stable disease than in those with progressive disease. Combined administration of these agents is feasible with acceptable toxicity, and Phase II trials are warranted.
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PMID:Phase I trial of recombinant interleukin-2 and recombinant beta-interferon in refractory neoplastic diseases. 278 53

The authors performed a Phase I study to assess the toxicity and hematologic effect of recombinant human interleukin-2 (rIL-2) in seven children with advanced malignancies. The rIL-2 was given as a bolus injection of 1 or 3 X 10(6) U/m2/dose three times a week (Monday, Wednesday, and Friday) for 3 weeks. No life-threatening toxicity occurred with the dose of 1 X 10(6) U/m2 of rIL-2. At a dose of 3 X 10(6) U/m2, therapy had to be terminated due to cardiovascular toxicity in two patients. Toxic effects at low-dose rIL-2 included fever, nausea, vomiting, and mild hypotension. High-dose rIL-2 toxicity included fluid retention, increased creatinine, oliguria, elevated liver enzymes, and significant hypotension. Immunologic studies showed that rIL-2 caused a drop in the number of circulating peripheral blood mononuclear cells, T-cells, and natural killer cells which returned to pretherapy levels or above by 24 to 48 hours. The rIL-2 exerted no growth or stimulatory activity on the leukemic cell population. To the authors' knowledge, this is the first report of a Phase I study of IL-2 therapy in children.
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PMID:A phase I study of interleukin-2 in children with cancer and evaluation of clinical and immunologic status during therapy. A Pediatric Oncology Group Study. 278 1

Twenty-seven patients with metastatic cancer were treated with a daily continuous intravenous (IV) infusion of recombinant human interleukin-2 (rhIL-2) along with daily intramuscular recombinant interferon-alpha-2a (rIFN-alpha-2a) 4 days per week for 4 weeks with repeated treatment after 2 to 4 weeks of rest. The maximum-tolerated dose (MTD) was 3 million U/m2/d of rhIL-2 with 5 to 10 million U/m2/d of rIFN-alpha-2a. The dose-limiting toxicities are moderate hypotension requiring low doses of pressors and chronic fatigue associated with decreased performance status. Other common side effects included fever, chills, fluid retention, nausea/vomiting, erythrodermia, weight loss, elevated liver transminase levels, anemia, thrombocytopenia, and CNS toxic effects. There were seven objective responses among 25 evaluable patients. Four major responses (one complete response and three partial responses) were observed among 10 patients with melanoma treated with the MTD level. These data suggest that for cancer patients, concomitant rhIL-2 and rIFN-alpha-2a therapy is tolerable and has manageable side effects. Further phase II studies will be needed to define the antitumor activity of this combination.
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PMID:Concomitant administration of recombinant human interleukin-2 and recombinant interferon alpha-2A in cancer patients: a phase I study. 280 85

Recombinant human interleukin-2 (rIL-2) was administered to 34 patients with advanced malignancy. Three schedules of rIL-2 administration employed were as follows: (A) 2-hr iv infusion of 6.7 X 10(5) U/m2/day (A1, 6 cases) or 2.2 X 10(6) U/m2/day (A2, 8 cases) for five consecutive days; (B) 24-hr continuous iv infusion of 3.3 X 10(5) U/m2/day (B1, 3 cases), 6.7 X 10(5) U/m2/day (B2, 7 cases) or 1.1 X 10(6) U/m2/day (B3, 5 cases) for 28 consecutive days; and (C) 24-hr continuous iv infusion of 6.7 X 10(5) U/m2/day (C, 5 cases) for 5 consecutive days per week for four weeks. The common side effects were fever (79%), eosinophilia (61%), malaise (56%), erythema or rash (50%), chills (38%) and nausea or vomiting (35%), with the dose-limiting toxicities being hypotension in group A, and renal dysfunction with fluid retention in groups B and C. In the case of 2-hr iv infusion, rIL-2 was rapidly cleared from the plasma, with a half life of about 30 min, while in the case of 24-hr continuous infusion, more than 1 U/ml serum IL-2 activity was maintained for 14 days in group B3. Natural killer (NK) and lymphokine-activated killer (LAK) activities were augmented by rIL-2 administration in patients of groups A, B3 and C. In eight patients of group B, NK and LAK activities transiently decreased after rIL-2 administration, and recovered by day 3. The percentage of IL-2 receptor and Leu HLA-DR positive cells reached the peak level on day 7 in group B. In patients of group C, the percentage of Leu HLA-DR positive cells as well as NK and LAK activities increased upon rIL-2 administration and decreased during an intermission of two days. However, the percentage of rIL-2 receptor positive cells increased during the intermission of rIL-2. The most effective schedule of rIL-2 administration was considered to be the schedule of group C on the basis of this study.
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PMID:Three schedules of recombinant human interleukin-2 in the treatment of malignancy: side effects and immunologic effects in relation to serum level. 312 1


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