Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028961 (oliguria)
 1,847 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Published data indicate that when recombinant interleukin-2 (rIL-2) is administered to children as a 15-min i.v. bolus, doses of 18 x 10(6) IU/m2 are poorly tolerated, requiring intensive care unit (ICU) management of IL-2-induced hypotension. We administered rIL-2 as a 1- or 2-h i.v. infusion to 11 children with malignancies refractory to conventional therapy. IL-2 was given every Monday/Wednesday/Friday for 3 weeks. Four children received 12 x 10(6) IU/m2/dose, four received 18 x 10(6) IU/m2/dose, and three received 24 x 10(6) IU/m2/dose (1 Cetus Unit = 6 IU). Fever, chills, flushing, nausea, vomiting, transient weight gain, and oliguria were observed at all three dose levels (not dose-limiting toxicities). Cardiovascular toxicity was significantly reduced compared to the bolus regimen. Mild hypotension was observed at all three dose levels; however, there was no severe dose-limiting hypotension. Because of reduced cardiovascular toxicity, IL-2 was safely administered on an outpatient basis. This regimen induced marginal transient increases in natural killer cell activity and lymphokine-activated killer cell activity. No measurable clinical tumor response was observed in any of the 11 children. The maximum-tolerated dose has not been reached. This regimen allows for a considerable cost reduction (outpatient care instead of ICU care) and safety, making further clinical trials on the use of IL-2 in children more feasible.
 ...
PMID:Phase I study of recombinant human interleukin-2 for pediatric malignancies: feasibility of outpatient therapy. A Pediatric Oncology Group Study. 150 55

Immunotherapy with interleukin (IL)-2 possesses great potential in the treatment of immune-mediated diseases and cancers. However, only a few reports on a small number of children have appeared in the literature. From March 1988 to March 1989, 11 children and adolescents were treated with IL-2. They included 1 patient with hepatocellular carcinoma, 1 with hepatoblastoma, 6 with childhood atopic dermatitis, and 3 with juvenile rheumatoid arthritis. The dosages ranged from 10,000 to 50,000 U/kg every 8 hours by intravenous drip. The following side effects were observed: anorexia, fever, and chillness (100%), general malaise (82%), irritability (64%), diarrhea (100%), nausea and vomiting (73%), weight gain (82%), edema (82%), abdominal distension (73%), oliguria (82%), cough (91%), dyspnea (27%), pleural effusion (40%), hypotension (82%), skin eruption (82%), oral ulcer (18%), enlarged liver (73%) liver function abnormalities (82%), renal function impairment (36%), electrolyte imbalance (73%), anemia (91%), thrombocytopenia (54%), leukopenia (18%), and eosinophilia (73%). Immunologically, numbers of natural killer cells were increased and natural killer and lymphokine-activated killer cell activities were augmented after IL-2 treatment. There was a tendency for serum levels of IL-2 and receptor IL-2 to decrease, especially in patients with atopic eczema. Ten patients (91%) completed one course (9 to 12 days) of therapy, and the remaining patient interrupted the treatment because of intolerable adverse effects. Clinically, complete remission for 3 months was obtained in 1 juvenile rheumatoid arthritis patient, transient improvement (2 to 6 weeks) in all atopic dermatitis patients, minor response in the hepatoblastoma patient, and no response in the patient with hepatocellular carcinoma.
 ...
PMID:Interleukin-2 immunotherapy in children. 217 36

Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.
 ...
PMID:Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. 221 99

Fifty patients with advanced melanoma received high-dose bolus and continuous infusion interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells in an attempt to improve the therapeutic index of this active but toxic therapy. Treatment began with up to nine bolus doses of IL-2 administered over 3 days. After 1 day of rest, patients underwent daily leukapheresis for 4 days, and the leukocytes were cultured with IL-2 in vitro to prepare LAK cells. Continuous infusion IL-2 was begun 1 day after the last leukapheresis and continued for up to 148 hours; LAK cells were administered on days 1, 2, and 4 of the infusion. Responding patients were eligible to receive up to two additional cycles of therapy at 3-month intervals. Most patients completed each cycle without dose reduction. One patient had a complete response and six patients had partial responses (14% response rate). The complete responder and three of the partial responders (8%) remain free from disease progression with follow-up of 21 to 24 months. Of these four patients with durable remissions, one had extensive liver and lymph node metastases, one had lymph node, pleural, and parenchymal lung metastases, and two had disease limited to lymph nodes or subcutaneous tissues. Seventeen patients (34%) required pressors for hypotension, three patients (6%) developed hemodynamically significant arrhythmias, and six patients (12%) developed dyspnea at rest, but none required intubation and there were no treatment-related deaths. Unacceptable toxicity developed in two patients during bolus IL-2 administration and therapy was aborted; both returned to baseline status within 4 days of discontinuing IL-2. Fever, oliguria, and elevated creatinine or transaminase levels occurred frequently but were also transient. Despite less frequent severe toxicity with this modified regimen, these results confirm the ability of IL-2 and LAK cell therapy to induce durable remissions in some patients with advanced melanoma.
 ...
PMID:Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells. 219 16

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.
 ...
PMID:A phase I clinical trial of recombinant interleukin-2 by periodic 24-hour intravenous infusions. 278 32

The systemic administration of recombinant interleukin-2 (IL-2) either alone or in combination with lymphokine activated killer cells is a new approach to the immunotherapy of metastatic cancer in man. Renal toxicity is often a dose-limiting side effect of IL-2 administration. This prospective study of 17 consecutive patients receiving parenteral high dose IL-2 documents a reversible syndrome of hypotension, oliguria, fluid retention, azotemia and very low urinary excretion of sodium (median FeNa of 0.04%). The median nadir urinary uric acid to urinary creatinine ratio during IL-2 therapy was 0.2. This IL-2 regimen induces a reversible renal hypoperfusion syndrome (pre-renal azotemia) without evidence of acute uric acid nephropathy. Hypophosphatemia [median serum phosphorus of 1.9 mg/dl (0.61 mmol/l)] prompted further study of tubular function. Urinary excretions of phosphorus, calcium and magnesium were very low. Arterial blood gases revealed hyperventilation without alkalemia. The hypophosphatemia probably reflects increased utilization of inorganic phosphorus by rapidly proliferating lymphoid cells.
 ...
PMID:Metabolic and renal effects of interleukin-2 immunotherapy for metastatic cancer. 326 37

We studied the effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells plus interleukin-2 or therapy with high-dose interleukin-2 alone in 157 patients with metastatic cancer for whom standard therapy had proved ineffective or no standard effective treatment was available. One hundred eight patients were treated with 127 courses of LAK cells plus interleukin-2, and 49 patients were treated with 53 courses of high-dose interleukin-2 alone. Of 106 evaluable patients receiving LAK cells plus interleukin-2, 8 had complete responses, 15 had partial responses, and 10 had minor responses. The median duration of response was 10 months among those with complete responses and 6 months among those with partial responses; the patient with the longest complete response was still in remission 22 months after treatment. Of 46 evaluable patients treated with high-dose interleukin-2 alone, 1 had a complete response (remission greater than 4 months), 5 had partial responses (2, greater than 3, greater than 5, 7, and greater than 11 months), and 1 had a minor response. Seven of the total of nine complete responses still remain in remission. Hypotension, weight gain, oliguria, and elevation of bilirubin and creatinine levels were common, but these side effects resolved promptly after interleukin-2 administration was stopped. There have been four treatment-related deaths among these 157 patients. This immunotherapeutic approach can result in marked tumor regression in some patients for whom no other effective therapy is available at present. Determining its ultimate role in cancer therapy awaits further attempts to increase the therapeutic efficacy of treatment and decrease its toxicity and complexity.
 ...
PMID:A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. 349 32

Adoptive transfer of autologous lymphokine-activated killer cells in conjunction with recombinant interleukin-2 in patients with advanced cancer has produced significant regression of metastatic disease in selected patients. We analyzed the effects of interleukin-2 regimens on renal function in 99 consecutive patients. Interleukin-2 therapy with or without lymphokine-activated killer cells was associated with varying degrees of hypotension, fluid retention, azotemia, oliguria, and low fractional sodium excretion. After the patients completed the interleukin-2 regimens, their renal function improved promptly. Renal function values returned to baseline levels within 7 days in 62% of patients, within 14 days in 84%, and within 30 days in 95%. Pretherapy serum creatinine values above 1.4 mg/dL predicted the severity of azotemia and prolonged duration of renal functional recovery, interleukin-2 therapeutic regimens induce prerenal azotemia. Careful selection of patients and early detection of adverse physiologic changes may alleviate the side effects of interleukin-2 therapy.
 ...
PMID:Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer. 349 13

Recombinant interleukin (IL)-2 is a newly approved immunoregulatory protein produced by lymphocytes that exhibits a wide range of immunologic effects. It is a true biologic response modifier in that is has no known direct antitumor activity, but mediates its cytotoxicity through activation of effector cells including T cells, natural killer cells, and lymphokine-activated killer cells. Recombinant IL-2 has demonstrated activity in patients with renal cell carcinoma and melanoma, with objective response rates of approximately 15-20%. The median duration of response in renal cell carcinoma is 23 months. Toxicity experienced with high-dose IL-2 can be significant. The most common dose-limiting toxicities are hypertension, weight gain, oliguria, respiratory insufficiency, and neurotoxicity. These effects are generally manageable and reversible on discontinuation of therapy. Administration of low-dose IL-2 has emerged as a means of substantially reducing toxicity. At least in renal cell carcinoma, it appears that the response rate to low-dose IL-2 is comparable to that with higher dosages.
 ...
PMID:Recombinant interleukin-2. 788 67

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)
 ...
PMID:Adverse reactions to intravenous contrast media in patients treated with interleukin-2. 847 95


1