Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyinosinic-polycytidylic acid, a double-stranded ribonucleic acid that is a potent inducer of interferon production, was used in a stabilized form to treat 11 patients with metastatic renal cell carcinoma. Seven patients completed a full course of 8 infusions at maximum tolerated dosage. All patients experienced transient fever and marked fatigue. Anorexia was mild. Transient leukopenia occurred in 3 patients and reversible elevation in creatinine was observed in 1. All 4 patients with brain metastases became lethargic, and 3 died during or shortly after therapy. Only 2 patients demonstrated measurable total regression of isolated metastases (pleural/pulmonary in 1 and bone in 1) but in both metastases at other sites progressed. No partial regressions were seen. Metastases at all other sites (liver, brain and renal fossa) progressed during therapy. Patients who appeared to respond and who performed best during therapy generally demonstrated a higher performance status initially. Expression of natural cytotoxicity in in vitro testing did not correlate with a demonstrated response to treatment.
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PMID:Immunotherapy of metastatic renal cell carcinoma with polyinosinic-polycytidylic acid. 380 4

Twenty patients with measurable metastatic renal cell carcinoma (RCC) were were treated with interferon alfa-2a (Roferon-A), 36 X 10(6)U intramuscularly 3 times weekly, alone (2 patients) or in combination with vinblastine, 0.10-0.15 mg/kg intravenously every 2 to 3 weeks. Objective responses in the lung, bone, liver, and lymph node metastases were seen in 6 of 18 evaluable patients. Dose reduction of interferon alfa-2a was necessary in 19 of the 20 patients due to intolerable flu-like side effects and fatigue. Bone marrow suppression and increase of gamma-GT represented the most often observed objective toxicity. The preliminary results of this combination treatment in RCC are promising and warrant randomized studies exploring the role of vinblastine. The dose of interferon alfa-2a should be reduced by 50% to avoid excessive toxicity and to maximize patient compliance.
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PMID:Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma. 394 41

An extended phase II trial of human leukocyte (alpha) interferon was done in 48 patients with measurable metastatic renal cell carcinoma, 43 of whom were evaluable. Of these patients 1 (2.5 per cent) had a complete response that was maintained after 19 months, 6 (14 per cent) had a partial response and an additional 23 per cent had either a minimal response or stabilization of previously growing metastases for greater than 3 months. Toxicity caused termination of treatment in only 1 patient and generally was tolerable. Major toxicity consisted of fever (80 per cent), fatigue (80 per cent) and hematologic toxicity (42 per cent), which was severe in only 2 patients. Characteristics of patients responding to therapy were good performance status, previous nephrectomy and metastases limited to the lungs. The results achieved with human leukocyte interferon were superior to those achieved by immunotherapy or chemotherapy at this and other institutions, and further trials are warranted.
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PMID:The treatment of renal cell carcinoma with human leukocyte alpha-interferon. 664 83

The conditions of ten patients with metastatic renal cell carcinoma were serially evaluated by neuropsychiatric examination to determine the nature of the fatigue-asthenia symptoms resulting from human leukocyte interferon alpha therapy. The majority of the patients had moderate to severe behavioral changes and mild to moderate cognitive, affective, and personality changes within the first week of daily intramuscular administration of 3 X 10(6) units of interferon. This descriptive clinical study suggests that the intense fatigue may be a manifestation of a complex neurotoxicity, most suggestive of frontal lobe changes, and resulting in neurasthenia syndrome with reversible impairment of some higher mental functions.
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PMID:Neuropsychiatric manifestations of human leukocyte interferon therapy in patients with cancer. 674 98

A phase II multiinstitutional clinical trial was conducted to evaluate the safety and efficacy of the subcutaneous outpatient administration of recombinant human interleukin-2 and alpha-interferon in patients with progressive metastatic renal cell carcinoma. One hundred and forty-five patients were entered on this study between October 1989 and May 1991. Among 134 patients evaluable for treatment response, there were six complete (4.5%) and twenty partial (14.9%) responders, with an overall response rate of 19.4% (95% confidence interval, 13-26%). The median duration of complete remissions was 228 (range 51(+)-520+) days; the median duration of partial tumor regressions was calculated at 226 (range 112-473+) days. The overall median survival from start of therapy was 14.2 (range 1-23+) months. Fever, chills and general fatigue occurred in the majority of patients treated and were measured at grade II, III and IV in up to 55%, 24% and 3% of all evaluable patients, respectively. Three patients each developed grade III hypotension, dyspnea and diarrhea; two patients each had grade III and grade IV elevations of alkaline phosphatase; two and one patients respectively, exhibited grade III anemia and grade IV thrombocytopenia; two patients experienced severe cutaneous toxicity. The majority of patients received treatment in the outpatient setting. In summary, the outpatient use of subcutaneous interleukin-2 and alpha-interferon was effective in patients with advanced metastatic renal cell carcinoma; it was associated with less toxicity and thus, could improve the therapeutic index of interleukin-2 based biologic therapy when compared against high dose intravenous therapy.
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PMID:Subcutaneous recombinant interleukin-2 and alpha-interferon in patients with advanced renal cell carcinoma: results of a multicenter Phase II Study. 780 70

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

The combination of interleukin-2 (IL-2) and interferon-alpha-2a (IFN-alpha-2a) has synergistic bioactivity in numerous preclinical model systems. Thirty-nine patients with metastatic renal cell cancer were treated with continuous intravenous infusion IL-2 for 4-5 days plus intramuscular IFN-alpha-2a 2-3 days a week for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Thirty-one of the 39 patients were assessable for response determination. Response rate (six complete+seven partial remissions) was 33.3% for all patients, or 41.9% when the analysis was restricted to the 31 evaluable patients. Three patients were unable to tolerate treatment due to anorexia, weight loss, and severe fatigue. This therapy was relatively well tolerated in the outpatient setting in the other patients despite fever, chills, fatigue, anorexia, and weight loss. There was no correlation of response with site of metastases or bulk of disease.
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PMID:Interleukin-2 and interferon-alpha-2a outpatient therapy for metastatic renal cell carcinoma. 831 97

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

We report on the clinical course of 15 patients with metastatic renal cell carcinoma (RCC) who were treated with recombinant beta-interferon as part of a phase I-II study. There were no objective responders among the 15 patients treated with recombinant beta-interferon at an i.v. dose escalating from 90 X 10(6) U given three times a week until there was documented disease progression or complete response (CR). Overall median survival was 24 months. One patient refused further treatment after 7 weeks. The major side effects of treatment included cardiovascular events (20%), mental status change requiring cessation of drug (6.7%), and grade 3 headaches/myalgias (26.7%). There were no life-threatening side effects observed; however, cardiac events led to the termination of treatment in three patients. Other minor toxicities included fatigue (46.7%), proteinuria (60%), diarrhea (6.7%), nausea and vomiting (13.3%), persistent fever (6.7%) and transient visual disturbance (6.7%). Thus, at our institution, in a cohort of 15 patients with metastatic RCC, recombinant beta-interferon when given i.V. at a dose < or equal to 720 X 10(6) U three times per week, yielded no clinical antitumor activity. A review of the literature on the use of beta-interferon for metastatic RCC suggests that there may be some efficacy, but our experience with escalating i.v. doses < or equal to 720 X 10(6) U given three times a week does not support it. Moreover, at these doses, one may find serious cardiovascular events although further studies need to be done in order to clearly define dose-related side effects as well as optimal efficacy-to-toxicity ratio.
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PMID:Recombinant beta-interferon in the treatment of patients with metastatic renal cell carcinoma. 861 Jun 47


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