Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concomitant generation of macrophage-mediated suppressive events, as documented by the increase in neopterin and soluble interleukin-2 (IL-2) receptor (SIL-2R), and the enhanced production of cortisol, would represent the most investigated phenomena responsible for the reduced anticancer efficacy of IL-2 immunotherapy in humans. Based on our preliminary experimental studies suggesting a modulatory role of IL-3 on immune and endocrine effects induced by IL-2, a study was performed to evaluate the influence of IL-3 on biological effects of IL-2 cancer immunotherapy. We have evaluated 12 immunotherapeutic courses with IL-3 plus IL-2, which were performed in 6 patients with metastatic non-small cell lung cancer. The results were compared to those seen in 22 courses with IL-2 alone, carried out in 12 patients with metastatic non-small cell lung cancer. IL-3 was given intravenously at a daily dose of 1 microgram/kg/b.w. at 6 p.m. for 14 consecutive days, starting 7 days before IL-2. IL-2 was given subcutaneously at a dose of 3 million IU twice/daily for 5 days/week for 3 weeks. The increase in serum levels of the specific macrophage marker neopterin, induced by IL-2, was completely blocked by IL-3. The IL-2-induced SIL-2R rise was significantly lower during IL-3 plus IL-2 than under IL-2 alone. The increase in cortisol levels in response to IL-2 was neutralised by IL-3. The increase in lymphocyte, T lymphocyte, natural killer (NK) cell, activated T lymphocyte and eosinophil mean number was significantly higher during IL-3 plus IL-2 than during IL-2 alone. Episodes of fever, asthenia, anorexia, vomiting, anaemia and thrombocytopenia were significantly more frequent in patients receiving IL-2 alone than in those treated with IL-3 and IL-2. This preliminary study would suggest that IL-3 may improve the tolerability of IL-2 immunotherapy and enhance the biological antitumour properties of IL-2 by neutralising cortisol increase and macrophage-mediated suppressive events, with a following potential amplification of Il-2 anticancer efficacy.
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PMID:In vivo biological results of the association between interleukin-2 and interleukin-3 in the immunotherapy of cancer. 839 Aug 45

Seventy patients consecutively admitted to a single institution were treated with high-dose interleukin-2 (IL-2) and analyzed for determining the incidence and risk factors associated with reactions to i.v. contrast media. Patients with metastatic renal cancer (n = 44) or melanoma (n = 26) received 74 cycles of IL-2 administered at 2 to 6 x 10(6) U/m2/d for 10-21 days either alone or with lymphokine-activated killer (LAK) cells or tumor-infiltrating lymphocytes (TILs). Seventy-four computed tomography (CT) scans were performed before administration of IL-2; and 74, 59, and 35 CT scans were performed, respectively, 2, 6, and 10 weeks after administration of IL-2. Of the 168 scans performed after therapy with IL-2, non-ionic media were used in 110 and ionic media were used in 58. There were no reactions before administration of IL-2, but there were nine reactions after therapy with IL-2. Reactions to contrast media occurred 1-4 hours after media infusion and included fever, chills, emesis, diarrhea, rash, wheezing, hypotension, edema, and oliguria. Hospitalization was required in seven cases, including intensive care unit support in four, but all patients recovered fully. Contrast reactions were more frequent 2 weeks after therapy with IL-2 (eight of 74 scans, 11%) compared with 6 weeks after IL-2 (one of 59 scans, 1.7%), but the difference was not statistically significant (McNemar's test). Six patients who reacted to contrast 2 weeks after IL-2 treatment received contrast 4 weeks later: five had no reaction and only one experienced a reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adverse reactions to intravenous contrast media in patients treated with interleukin-2. 847 95

A total of 29 patients with stage IV colorectal cancer were entered into a phase II trial of bolus interleukin-2 (IL-2) and interferon-alpha (IFN alpha) (3 x 10(6) U/m2 of each cytokine given i.v. q8h x 15 doses and repeated in 2 weeks). Immunologic parameters measured on isolated peripheral blood lymphocytes revealed increased activated T cells with upregulated natural killer and lymphokine-activated killer activity. Among 24 evaluable patients, there were 4 partial responses (17%) of short duration ( < or = 6 months). Three of the responding patients had been refractory to prior chemotherapy. Overall median survival in the 24 evaluable patients was 18.5 months. Therapy necessitated an inpatient setting, with the most common toxicities being hypotension, hepatic insufficiency, fever, hypocalcemia, nausea/vomiting, and renal insufficiency. There were two treatment-related deaths. Because neither IL-2 nor IFN alpha alone has significant activity against colorectal cancer, the responses observed in this study suggest a potential synergistic effect between the two cytokines. However, the toxicity and short duration of response without survival benefit do not support the routine use of this regimen as a therapeutic modality for this tumor histology.
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PMID:A phase II trial of interleukin-2 and interferon-alpha in the treatment of metastatic colorectal carcinoma. 868 Jun 53

The toxicity and clinical response to treatment with the combination of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in patients with metastatic melanoma was evaluated. From May 1993 through February 1994, 20 patients were treated with 24 courses of IFN-gamma with or without IL-2. A 7-day course of subcutaneous IFN-gamma alone was administered to cohorts of two or three patients each at doses of 0.1, 0.2, or 0.3 mg/m2. Thirteen patients received escalating doses of IFN-gamma between 0.2 and 0.5 mg/m2 followed by the intravenous (i.v.) administration of IL-2 (720,000 IU/kg) given three times a day. A treatment course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated by a 10-day interval. Five additional patients were treated with five courses of IFN-gamma, IL-2, and tumor-infiltrating lymphocytes (TILs). All patients treated had the diagnosis of metastatic melanoma. The maximal tolerated dose of subcutaneous IFN-gamma was established at 0.3 mg/m2 with dose-limiting hepatotoxicity. Immunohistochemistry analyses showed detectable upregulation of MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received the combination of IFN-gamma and IL-2 had responses, one partial and one complete response. The duration of response was 7 months for the partial response and 12 months for the complete response. IFN-gamma was tolerated with minimal side effects of nausea, vomiting, malaise, and decreased hematopoiesis. No increased toxicities were found with the combination treatment, as compared with IL-2 alone. One death occurred on the third day of treatment with IFN-gamma alone from hemorrhage into brain metastases. There were no responders in the five patients who received the combination treatment of TIL, IL-2, and IFN-gamma. From these findings, we conclude that further studies looking at this combination treatment are not warranted.
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PMID:Combination therapy with interferon-gamma and interleukin-2 for the treatment of metastatic melanoma. 885 24

Because interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) act synergistically in vitro in the generation of lymphokine-activated killer (LAK) cells. we initiated a clinical trial of these lymphokines in combination. Twenty patients with advanced malignancy were treated at fixed dose levels of recombinant IFN-gamma given by intramuscular (i.m.) injections once a day and recombinant IL-2 given by an intravenous (i.v.) bolus injection 3 times a day for 7 days after a 3-day treatment with fixed doses (250 micrograms/m2/day) of IFN-gamma alone. A minimum of four patients were treated at each of the four dose levels studied. The side effects of the combination therapy were similar to those seen with individual lymphokines and included fever and chills, myalgia, headache, fatigue, nausea. vomiting, peripheral edema, skin rash, and hypotension. The maximum tolerated dose for the combination after a fixed dose of IFN-gamma was 2 x 10(5) U/M2/day (10 micrograms/m2/day) of IFN-gamma and 3 x 10(6) U/M2/day of IL-2, with fluid retention as the dose-limiting toxicity. Whereas natural killer (NK) or LAK activity or both were significantly increased in four of eight patients studied, only one patient with renal cell cancer had a minor response for four treatment cycles. We conclude that combination therapy with cytokines IL-2 and IFN-gamma given in this schedule had manageable toxicity and exhibited immunomodulatory effects in some patients but had no significant antitumor activity in this patient population.
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PMID:Recombinant interleukin-2 in combination with recombinant interferon-gamma in patients with advanced malignancy: a phase 1 study. 910 17

Adoptive immunotherapy (AI) with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) is an antineoplastic modality in which immune-activated cells are administered to a host with advanced cancer in an attempt to mediate tumor regression. Levamisole (LEV), an immune stimulant, has been suggested to have therapeutic effectiveness in a variety of cancers. After a phase I trial of recombinant IL-2 plus LEV, a phase II trial of this combination was conducted in patients with advanced malignant melanoma. Nineteen patients were entered in the trial. They received IL-2 at 3 x 10(6) U/m2 subcutaneously daily x 5 plus LEV 50 mg/ m2 orally three times daily (p.o. t.i.d.) x 5. Patients were reevaluated at four-week intervals. None of the patients achieved a partial or complete regression (PR, CR). The median time to treatment failure (refusal, progression, or off study due to toxicity) was 56 days. Grade IV toxicities included vomiting (3 patients), lethargy (1 patient), and musculoskellar pain (1 patient). This regimen is not recommended for further testing in patients with advanced malignant melanoma.
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PMID:Phase II study of combined levamisole with recombinant interleukin-2 in patients with advanced malignant melanoma. 934 34

In this study, the safety with efficacy of infusional 5-fluorouracil (5-FU) (200 mg/m2/day) combined with subcutaneous interleukin-2 (IL-2) (9-27 x 10(6) IU/day) was investigated in patients with metastatic and renal cancer. In the 24 patients evaluated, the overall response rate was 17% (1 CR, 3 PR). The major toxicity was the vascular leak syndrome (VLS) which required inotrope support in 18% of treatment cycles. Other common systemic toxicities were vomiting, oedema and malaise (grades 1 and 2). There was no enhanced or novel toxicity from the combination of drugs. Based on this study, it will be feasible to use infusional chemotherapy with other cytokine combinations.
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PMID:A phase II study of continuous infusional 5-fluorouracil (5-FU) and subcutaneous interleukin-2 (IL-2) in metastatic renal cancer. 937 97

A prospective phase II trial was carried out to define the activity of a low-dose subcutaneous regimen of interleukin-2 (IL-2) and interferon alpha-2b (IFN-alpha) in combination with intravenous administration of vinblastine (VLB) in patients with metastatic renal cell cancer (RCC). Thirty-one patients with advanced RCC who had received no prior biochemotherapy were treated with IL-2 4.5 MU x 2/24 h thrice weekly for 2 weeks, IFN-alpha 3 MU/24 h thrice weekly (alternating days) for 2 consecutive weeks and VLB 4 mg/m2 every 3 weeks. Patients were to have a 1-week rest period after each 2 weeks of therapy with cytokines. Treatment was repeated every 3 weeks. Maximum duration of treatment was 1 year. Treatment was administered on an outpatient basis. There were 4 complete (12.9%) and 8 partial responses (25.8%), with an overall response rate of 38.7%. The median duration of response was 6.5 months. Responses were seen in lung, lymph nodes, bones, liver and other tumor metastases. Toxicity was mild to moderate, consisting of fever, anorexia, malaise and nausea-vomiting in > 80% of patients. Hypotension and transient alopecia occurred in > 20% of patients. Liver enzyme elevation was frequently observed. Treatment-induced eosinophilia occurred in the majority of patients, while in 52% of patients granulocytopenia grade II and grade III did not require dose modification of drugs. Transient inflammation and local induration at the injection sites was observed in the majority of patients. None of the patients experienced major VLB-related toxicity and no toxic deaths occurred. This three-drug combination immunochemotherapy may be a promising regimen with modest toxicity in advanced RCC.
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PMID:An outpatient phase II study of subcutaneous interleukin-2 and interferon-alpha-2b in combination with intravenous vinblastine in metastatic renal cell cancer. 942 69

Patients treated with high doses of interleukin-2 (IL-2) develop profound anorexia, malaise, loss of energy, mucositis, nausea, and vomiting, which may contribute to poor nutrition. We hypothesized that total parenteral nutrition (TPN) administration would ameliorate these changes and could improve fluid and electrolyte balance. A retrospective analysis of protein and energy intake was performed in 21 sequential patients who received a normal diet (controls) and 16 subsequent patients who received TPN during IL-2 treatment. The effect of TPN on laboratory abnormalities induced by IL-2 was also evaluated. Within 24 h of starting IL-2, mean energy intake declined to 2.5-2.8 kcal/kg in controls in contrast to the energy intake of 25-29 kcal/kg in patients receiving TPN. Protein nutrition was affected in a similar fashion, with a markedly lower protein intake in controls (0.08-0.12 g/kg) than in the TPN group (1.02-1.10 g/kg). TPN improved serum calcium and potassium concentrations, particularly during spontaneous diuresis after completion of IL-2 treatment. Unexpectedly, TPN decreased the frequency and severity of cholestatic jaundice caused by IL-2. Patients receiving TPN had an increased propensity for hyperglycemia and hypophosphatemia. High-dose intravenous bolus IL-2 therapy resulted in a markedly negative nutritional balance in control patients. A brief period of TPN during IL-2 treatment was well tolerated and corrected calorie and protein malnutrition. TPN administration also improved control of serum electrolytes. TPN did not adversely affect tumor progression or patient survival.
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PMID:Effects of total parental nutrition (TPN) during high-dose interleukin-2 treatment for metastatic cancer. 945 39

Natural killer (NK) cells may be expanded in vivo with a prolonged course of daily subcutaneous interleukin-2 (IL-2). However, cellular activation requires higher concentrations of IL-2 than are achieved with low-dose therapy. The objective of the current trial was to determine the toxicity and immunological effects of periodic subcutaneous intermediate-dose IL-2 pulses in patients receiving daily low-dose therapy. A group of 19 patients were treated with daily subcutaneous low-dose IL-2 at 1.25 x 10(6) International Units (1.25 MIU) m(-2) day(-1). After 4-6 weeks, patients received escalating 3-day intermediate-dose IL-2 pulses administered as single daily subcutaneous injections, repeated at 2-week intervals. The maximum tolerated pulse dose was 15 MIU m(-2) day(-1), with transient hypotension, fatigue, and nausea/vomiting dose-limiting. Subcutaneous IL-2 resulted in in vivo expansion of CD56+ NK cells (796+/-210%) and CD56bright natural killer (NK) cells (3247+/-1382%). Expanded NK cells coexpressed CD16, and showed lymphokine-activated killer activity and antibody-dependent cellular cytotoxicity in vitro. Intermediate-dose pulsing resulted in serum IL-2 concentrations above 100 pM. Cellular activation was suggested by rapid margination of NK cells following pulsing, coincident with peak IL-2 levels, with return to baseline by 24 h. In.addition, interferon gamma production in response to lipopolysaccharide was augmented. Subcutaneous daily low-dose IL-2 with intermediate-dose pulsing is a well-tolerated outpatient regimen that results in in vivo expansion and potential activation of NK cells, with possible application in the treatment of malignancy and immunodeficiency.
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PMID:Evaluation of natural killer cell expansion and activation in vivo with daily subcutaneous low-dose interleukin-2 plus periodic intermediate-dose pulsing. 975 16


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