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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase II trial of intermittent high-dose recombinant interleukin-2 (rIL-2) was initiated to evaluate the response rate, remission duration, and toxic effects in patients with measurable metastatic renal cell carcinoma. The rIL-2 was administered as a bolus intravenous infusion at a dose level of 10.0 x 10(6) U/m2 three times weekly, preceded by indomethacin (50 mg orally). Dose reductions of rIL-2 for hypotension and other grade 3 or 4 toxic effects were permitted. Forty-four patients were entered and 41 were eligible. Previous treatment included nephrectomy (23 patients), radiation therapy (seven), and hormone therapy (three). Most toxic effects observed were moderate and included nausea, vomiting, anorexia (85%); hypotension (85%); fever, chills (78%); central nervous system changes (24%); myelosuppression (27%); and creatinine elevation (15%). Four instances of grade 4 toxicity were observed and included nausea, vomiting with dehydration; hypotension; and myocardial infarction. Thirty patients (73%) required dose adjustments because of toxicity. Five responses (12%) were seen, which included one complete and four partial. Sites of response included lung, liver, and soft tissue; the duration of response ranged from 2 to 20+ months. These results demonstrate that this schedule of rIL-2 can be administered in an outpatient setting, and can produce tumor regression in patients with metastatic renal cell carcinoma, including durable complete responses.
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PMID:Phase II trial of high-dose intermittent interleukin-2 in metastatic renal cell carcinoma: a Southwest Oncology Group study. 229 24

Continuous long-term 5-fluoro-2'-deoxyuridine (floxuridine; FUDR) infusion frequently causes severe and dose-limiting gastrointestinal toxicity when administered at a constant rate at commonly prescribed dose levels. In preclinical studies, a circadian infusion pattern peaking late in the daily activity phase was better tolerated and had superior antitumor activity than a constant infusion against a transplanted tumor. Based upon these data and upon other chronobiological cytokinetic and pharmacologic considerations, we compared a circadian patterned variable rate infusion with a maximal flow rate in the late afternoon/early evening and minimum flow rate during the early morning hours to a constant rate infusion in 54 patients with widespread cancer. All FUDR infusions were administered using an implanted drug pump. In a pilot crossover study and a second randomized trial, patients with metastatic malignancies treated with equal dose intensities experienced less frequent and less severe diarrhea, nausea, and vomiting following variable rate infusion. In a third study, the dose intensity of variable rate infusion was escalated stepwise to determine the maximum-tolerated dose. Patients receiving time-modified FUDR infusion tolerated an average of 1.45-fold more drug per unit time while evincing minimal toxicity. FUDR infusion was found to have activity against progressive metastatic renal cell cancer (RCC). Increased dose intensity achieved by optimal circadian shaping may improve the therapeutic index of infusional FUDR and may help control malignancies that are refractory to conventional chemotherapy.
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PMID:Circadian patterning of continuous floxuridine infusion reduces toxicity and allows higher dose intensity in patients with widespread cancer. 253 Mar 18

Sixteen patients with metastatic melanoma or metastatic renal cell carcinoma were treated with six weekly 24-hour infusions of recombinant interleukin-2. At least three patients were treated at each dose, beginning at 3.0 mU/m2 for 24 hours each week for 6 weeks. Subsequent patients were treated at 4.5, 6.0, 8.0, and 10.0 mU/m2 for 24 hours. The incidence of diarrhea, rigors, rash, edema, and symptomatic hypotension was positively correlated with dose level. Symptomatic hypotension was dose limiting at the 10-mU/m2 level. Fever, nausea, and vomiting were seen at each dose level and could not be correlated with dose level. Lymphopenia and eosinophilia were observed at the completion of each 24-hour infusion, and an increase in peripheral blood absolute lymphocytes and eosinophils was observed over the 6-week treatment period. No thrombocytopenia was observed. No change in delayed-type hypersensitivity (type IV) as determined by skin testing could be demonstrated at any dose level. Natural killer cell cytotoxicity of peripheral blood lymphocytes increased over the treatment period, but the increase was unrelated to dose level in the range studied. One minor response was documented in a patient with renal cell carcinoma.
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PMID:Phase I study of weekly 24-hour infusions of recombinant human interleukin-2. 326 71

Twenty-four patients with measurable metastatic renal cell carcinoma were treated in a phase I-II trial with alpha (human leukocyte) interferon (alpha IFN) and vinblastine (VBL) in combination. Patients received 3 X 10(6) IU/day of alpha IFN im 5 days/week and VBL iv weekly (at a starting dose of 0.15 mg/kg), with doses modified for toxicity. All patients were evaluable for toxicity; 23 patients were evaluable for response. An objective response rate of 13% was observed (three partial responses). An additional 22% of patients had minimal responses (five patients). The occurrence of nausea, vomiting, thrombocytopenia, hepatic dysfunction, and fever was comparable to that seen in previous studies of alpha IFN alone. Granulocytopenia, neurotoxicity, and malaise, however, occurred with increased frequency and severity. alpha IFN and VBL administered in combination in this dose schedule demonstrated activity similar to but toxicity greater than that seen in previous trials of alpha IFN alone.
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PMID:Treatment of renal cell carcinoma with alpha (human leukocyte) interferon and vinblastine in combination: a phase I-II trial. 397 56

Fourteen patients with metastatic renal cell carcinoma received methyl-G weekly at a starting dose of 600 mg/m2 (five patients) and 500 mg/m2 (nine patients) intravenously. All 14 patients are evaluable for response and toxicity. No antitumor responses were observed. Six patients achieved stabilization of disease for 8 to 42 weeks. Toxicity was nonhematologic and included nausea or vomiting (35%), fever with shaking chills (28%), diarrhea (21%), myalgia (63%), paresthesia (49%), and bilateral foot drop (7%). Methyl-G does not appear to have activity against renal cell carcinoma.
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PMID:Phase II trial of methyl-G (methylglyoxal bis-guanylhydrazone) in patients with metastatic renal cell carcinoma. 731 23

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.
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PMID:Phase II evaluation of merbarone in renal cell carcinoma. 786 Feb 33

A double-institution phase II study was performed in patients with metastatic renal cell carcinoma treated subcutaneously (s.c.) with interleukin 2 (IL-2) and alpha-interferon (INF-alpha). Thirty-eight patients were treated over a course of 7 weeks. Initially (day 1 + 2) patients received s.c. IL-2 at 18 x 10(6) IU m-2. During the following 6 weeks, patients received s.c. IL-2 at 3.6 x 10(6) IU m-2 for 5 days per week and s.c. INF-alpha at 5 x 10(6) for 3 days per week. Thirty-eight patients were evaluated for response. An objective response was seen in seven patients (18.4 +/- 12.3%), with one complete response and six partial responses. Median duration of response was 6.7 months. Toxicity could be evaluated in 38 patients and was limited. Mild to moderate toxicity included fever (97%), fatigue or malaise (76%), nausea or vomiting (50%), anorexia (32%), hypotension (26%), neurological disturbances (26%) and hypercreatininaemia (39%). In addition, four grade IV haematological toxicities were noted. No cardiac side-effects were seen. IL-2 and INF-alpha given by this schedule can be safely administered in an outpatient setting. The objective response rate was similar to our previous treatments with high-dose IL-2 given as a continuous infusion.
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PMID:Subcutaneous low-dose recombinant interleukin 2 and alpha-interferon in patients with metastatic renal cell carcinoma. 819 79

Sixteen patients with histologically-proven metastatic renal cell carcinoma (RCC) were treated after nephrectomy with a daily continuous 24-hour i.v. infusion of recombinant human interleukin-2 (rIL-2) at a dosage of 18 x 10(6) IU/m2 daily for 5 days per week and of recombinant interferon alpha-2a (rIFN-alpha 2a) 5 x 10(6) IU/m2 subcutaneously on days 2 and 4. The treatment cycles were repeated at 3-weekly intervals. Altogether 38 treatment cycles were given, but only 14/16 patients were evaluable for response rates. The main toxic side effects were fever, nausea, chills, anorexia, hypotension and hepatotoxic syndrome (Toxicity grades I-III, WHO). There were 3 objective responses among the 14 evaluable patients (21%); 2 patients have remained in complete remission for 12 and 8 months, respectively until now whilst 1 has shown a partial response for 21 months.
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PMID:[Combination therapy with recombinant interferon alpha-21 (rIFN alpha 2a) and recombinant interleukin 2 (rIL-2) in metastatic renal cell cancer]. 851 56

We report the clinical course of eight patients with metastatic renal cell carcinoma (RCC) who were treated with recombinant gamma-interferon (Immuneron) as part of a phase II-III study comparing the safety and efficacy of gamma-interferon with that of medroxyprogesterone acetate (Depo-Provera). There were no objective responders among the eight patients treated with recombinant gamma-interferon at an i.v. dose of 1 mg/m(2) daily for five days every other week for four weeks then 1 mg/m(2) three times a week given every other week until there was documented disease progression or complete response (CR). Overall median survival was 17.3 months (range 1.4 to 184). The major side effects of treatment included fever/chills (75%), mild anorexia and fatigue (75%), nausea/vomiting (80%), leukopenia (38%), and abnormal liver function tests (25%). There were no life-threatening side effects observed. At our institution, in a random cohort of eight patients with metastatic RCC, recombinant gamma-interferon when given at a dose of 1 mg/m(2) per day given three times per week on an every other week schedule yields no clinical antitumor activity. A review of the literature on the use of gamma-interferon for metastatic RCC suggests that low-dose combination therapy with other cytokines may yield the best response-to-side effect ratio. Higher doses yield more responses but an added cost of more toxicity.
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PMID:Single institution experience with recombinant gamma-interferon in the treatment of patients with metastatic renal cell carcinoma. 861 Jun 39

A phase II trial investigating the anti-tumour effects of recombinant human interleukin 6 (rhIL-6) in patients with metastatic renal cell cancer was carried out. RhIL-6 (150 microgram) was administered as a daily subcutaneous injection for 42 consecutive days on an outpatient basis. Forty-nine patients were studied, 12 with and 37 without previous immunotherapy. Forty patients were evaluable for response. A partial remission was noted in two patients, stable disease in 17 and progressive disease in 21. Toxicity was moderate and reversible and consisted mainly of fever, flu-like symptoms, nausea, weight loss and hepatotoxicity. Anaemia, leucocytosis and thrombocytosis and induction of acute phase protein synthesis were noted in most patients. In 15% of the patients anti-IL-6 antibodies developed, and were neutralising in only one patient. Baseline plasma IL-6 concentrations did not correlate with tumour behaviour before or after rhIL-6 treatment. In conclusion, rhIL-6 can be safely administered on an outpatient basis for prolonged period of time and has moderate, reversible toxicity. Its administration induces IL-6-antibody production in only a minority of patients. Antitmour effects of rhIL-6 in metastatic renal cancer are limited.
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PMID:Recombinant human interleukin 6 in metastatic renal cell cancer: a phase II trial. 861 81


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