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)

Interferon (IFN) related neurotoxicity includes somnolence and confusion, fatigue, lethargy, psychiatric symptoms, conceptual disorganization, neurological deficits, cortical blindness, coma and, rarely, death. The neurologic syndromes seem to be more common in elderly patients, following intramuscular or intravenous administration, at higher doses of frequent injections of IFN-alpha and in primary renal cell carcinoma. The duration of the treatment was not strongly related to neurotoxicity. Computed tomography findings were non-specific and included atrophy or periventricular lucencies. Electroencephalograph studies demonstrated a generalized increase in slow wave activity which returned to normal after cessation of treatment. Behavioral and mental changes in patients treated with IFN are warning signs, and indicate the need to withdraw treatment.
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PMID:Neurotoxicity of interferon-alpha. 128 26

The role of combination chemotherapy in the treatment of advanced non-small-cell lung cancer is controversial. At best, a small survival benefit can be achieved. Therefore, other treatment modalities are needed. On the basis of the promising treatment results with interleukin-2 (IL-2) -containing immunotherapy in renal cell cancer and melanoma, we performed a phase I-II study with IL-2 and interferon alpha (IFN-alpha). Eligible patients were treated with IL-2 18 x 10(6) IU/m2/day by continuous intravenous infusion (c.i.v.) for 3 days. On the same days, 5 x 10(6) U/m2/day IFN-alpha was given intramuscularly. After a rest period of 4 days, patients at the first dose level received IL-2 2.4 x 10(6) IU/m2/day c.i.v. for a period of 28 days, followed by 14 days' rest, 14 days' treatment, 7 days' rest, and a final treatment for 14 days. Patients at the second dose level were treated according to the same schedule, in which the dose of IL-2 was increased to 3.6 x 10(6) IU/m2/day. During low-dose IL-2 treatment, patients received IFN-alpha 5 x 10(6) U/m2/day on days 1 and 4 of each week. Eleven patients were admitted to the study, six at the first and five at the second dose level. Median age was 54 years; all patients had a performance status of 0 or 1. The most important adverse effects included anorexia, fatigue, nausea, and headache, which were not dose limiting. In the 11 patients treated, no responses were seen. Nine patients developed progressive disease during the first 5 weeks of treatment. We concluded that this regimen of IL-2 and IFN-alpha is ineffective.
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PMID:Interleukin-2 and interferon-alpha in the treatment of patients with advanced non-small-cell lung cancer. 132 67

Computed tomography (CT) was carried out in 31 patients 10-43 years after surgery for renal cell carcinoma, 10 belonging to a consecutive series of patients operated upon at one urological department 10 years previously. Twenty-eight patients were symptomless, and 3 had flank pain, severe fatigue and hematuria, respectively. Cancers in the remaining kidney were found 13-21 years after nephrectomy in 4 of 31 patients (12.9%). The 3 patients with symptoms were among these 4. An adenoma was found in 1 patient 10 years after nephrectomy. The cancers were treated by renal resection in 2 patients, multiple tumors made nephrectomy necessary in 1 patient and 1 patient was not operated upon because of disseminated disease. The adenoma indicated future checkup by CT. Three of the 4 new cancers had a dismal outcome. The renal parenchyma was found to be essentially normal in all the other 26 patients, irrespective of the widely varying time interval between nephrectomy and CT. Asynchronous bilateral renal cell carcinoma has a poor outcome which presumably can be improved by early diagnosis and aggressive treatment. CT is the method of choice for early detection and follow-up of renal tumors. It should be carried out every other year after nephrectomy for renal cell carcinoma.
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PMID:Bilateral asynchronous renal cell carcinoma. Computed tomography of the contralateral kidney 10-43 years after nephrectomy. 146 77

A clinical trial using interferon alpha 2b (IFN alpha-2b) for prophylactic therapy was done on 44 patients who had received nephrectomy for renal cell carcinoma. Principally, the daily intramuscular injection of 3 of 6 million units of IFN alpha-2b was done for 4 consecutive weeks after 2 weeks postoperatively and thereafter followed by injection once every 2 weeks. The clinical evaluation was done for the recurrence rate, the survival rate, the IFN alpha and IFN gamma producing ability, the activity of 2',5' oligoadenylate synthetase (2-5AS) and the side effect. Out of 44 cases entered, 42 were completely evaluable and recurrence was observed in 5 (11.9%) of the 42 cases. The recurrence rate was 5.5% and 16.4%, at the first and second year, respectively. Three (7.1%) of the 42 patients died. The survival rate was 97.6% at the first year, 89.7% at the second year for the followup study. The IFN alpha producing capacity was low in all of the 4 evaluable cases. The IFN gamma producing capacity was high in 3 cases and normal in 1 case. 2-5AS, the enzyme produced by IFN, was activated by IFN alpha-2b administration in all of the 4 evaluable cases. Side effects were observed in 24 (54.5%) of the 44 cases. The main side effect was fever. Leucopenia, general fatigue, appetite loss, temporary elevation of liver transaminase were also observed. However, there were only 5 cases (11.4%) in which administration of IFN alpha-2b had to be discontinued.
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PMID:[Clinical study of prophylactic therapy of interferon on postoperative renal cell carcinoma]. 152 80

The optimal schedule for recombinant interleukin-2 (rIL-2) administration is unclear. Because the clinical and immunological effects of prolonged continuous exposure to rIL-2 are unknown, we have conducted a phase I study to assess the toxicity and feasibility of continuous low dose infusion of rIL-2 (EuroCetus) using central venous access with a portable infusion device on an out-patient basis. Twenty-two patients entered the study, 13 with melanoma and nine with renal cell cancer, age range 26-66 years (median 51), performance status less than or equal to 1. They were treated with one of the following doses per m2 per 24 h: 0.18 x 10(6) IU, 0.6 x 10(6) IU, 1.8 x 10(6) IU, 3 x 10(6) IU, 6 x 10(6) IU and 9 x 10(6) IU. Toxicity was evaluable in 20 patients receiving greater than or equal to 3 weeks treatment duration or in whom treatment was discontinued prematurely because of toxicity. Constitutional symptoms consisting of fatigue, malaise and fever up to 40 degrees C without significant organ dysfunction occurred with doses greater than or equal to 1.8 x 10(6) IU m-2. The maximum tolerated dose was 6 x 10(6) IU m-2 24 h-1. In all patients toxicity reached a peak at 3 weeks and resolved thereafter despite continued rIL-2 treatment. Peripheral blood eosinophilia (up to 66% of white blood cell count) followed the same pattern. An infection of the central venous access occurred in 55% of the patients but this was mostly asymptomatic. Thirteen patients were treated greater than or equal to 6 weeks and were evaluable for tumour response. A partial remission occurred in a patient with melanoma with a dose of 1.8 x 10(6) IU rIL-2 m-2 24 h-1.
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PMID:A phase I study of prolonged continuous infusion of low dose recombinant interleukin-2 in melanoma and renal cell cancer. Part I: Clinical aspects. 158 2

We describe the surgical management and followup of 11 patients with local recurrence of renal cell carcinoma in the renal fossa, 10 of whom demonstrated no evidence of distant metastatic disease at the time of recurrence. Average interval to recurrence was 31 months from nephrectomy, with the majority of patients presenting with symptoms of weight loss, fatigue and lumbar discomfort. A total of 13 resections of recurrent carcinoma was performed with 3 immediate postoperative complications, including a retroperitoneal abscess, jejunal necrosis requiring resection and a duodenal obstruction requiring duodenojejunostomy. There were 2 postoperative deaths, 2 patients died of disseminated disease at 8 and 22 months, and 3 died of causes unrelated to cancer recurrence at 4 months, 6 months and 10 years. Four patients were without disease at a followup of 35, 46, 48 and 211 months. We include in this review a report on 1 patient who maintains a disease-free survival of 17 years after resection of a recurrent spindle cell carcinoma. We conclude that an aggressive surgical approach to recurrent renal cell carcinoma within the renal fossa can produce long-term disease-free survival and is justified when compared to the results reported for chemotherapy.
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PMID:Experience with fossa recurrence of renal cell carcinoma. 159 72

We conducted a phase I study of low-dose cyclophosphamide and recombinant interleukin-2 (rIL-2) in 66 patients with advanced cancer resistant to standard therapy. All patients were evaluable for toxicity and 46 patients were evaluable for antitumor response. Patients evaluable for antitumor response included 23 with malignant melanoma, 10 with renal cell carcinoma, 4 with colon cancer, and 9 with various other solid tumors. All patients received i.v. cyclophosphamide (350 mg/m2) on day 1 followed by rIL-2 via 15 min i.v. infusion on days 4-8 and 11-15. The doses of rIL-2 ranged from 6.0 to 36.0 x 10(6) IU/m2. Each treatment cycle consisted of 21 days and a total of 113 cycles was administered. The number of treatment cycles administered per patient ranged from 1 to 8. The dose-limiting toxicities associated with rIL-2 included altered mental status, arthralgias, diarrhea, fatigue, fever, hypotension, nausea/vomiting, and peripheral edema. Twelve patients (18%) were removed from the study secondary to toxicity. Among the evaluable patients, 2 (4%) (malignant melanoma, renal cell carcinoma) developed a partial remission, 13 (29%) maintained stable disease, and 31 (67%) developed progressive disease. We conclude that the combination of low-dose cyclophosphamide and rIL-2 is tolerable in most patients but our data do not suggest an improved response rate for the combination vs. rIL-2 alone.
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PMID:Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer. 159 14

Fifteen patients with advanced, measurable renal cell carcinoma entered a Phase II clinical trial of interleukin-2 (IL-2) (Teceleukin, Hoffmann-La Roche Inc., Nutley, NJ) and interferon (IFN) (Roferon A, Hoffmann-La Roche Inc.). IL-2 was administered by continuous infusion daily for 4 days and IFN was administered by intramuscular injection daily for 4 days; therapy continued for 4 weeks. Eight men and seven women were treated in this trial (median age, 61 years). Toxicity was moderate to severe with fatigue, nausea, vomiting, hypotension, and elevated blood urea nitrogen bunion and creatinine levels seen in all patients. Two patients achieved a complete remission and two patients achieved a partial remission. The median duration of response was 18 months. IL-2 and IFN is an active combination in the treatment of renal cell carcinoma and warrants further investigation.
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PMID:A phase II trial of interleukin-2 by continuous infusion and interferon by intramuscular injection in patients with renal cell carcinoma. 171 25

The National Cancer Institute (NCI) Canada Clinical Trials Group conducted a phase II study of recombinant tumor necrosis factor (rTNF) given intravenously daily for 5 days every other week, in measurable metastatic renal cell carcinoma. Two of 26 patients responded with responses lasting greater than 200 days. Toxicity was severe including rigors, fever, headache, fatigue, hypotension, and localized pain. We conclude that rTNF, given as described, has only modest antitumor activity in renal cell carcinoma and produces considerable toxicity. We plan no further studies of rTNF in this disease.
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PMID:A phase II study of recombinant tumor necrosis factor in renal cell carcinoma: a study of the National Cancer Institute of Canada Clinical Trials Group. 173 50

Recombinant interleukin 2 (IL-2) is a potent inducer of lymphokine-activated killer (LAK) activity directed against autologous and allogeneic tumors; these effects are mediated by CD3-negative, CD56-positive, and CD16-positive lymphocytes. Although IL-2 therapy has been associated with clinical responses, particularly in patients with renal cell carcinoma and melanoma, these responses have occurred with high, toxic doses of this cytokine. Since gamma-interferon (IFN-gamma) potentiates LAK activity in vitro and in animal models, we initiated a dose-escalating Phase I trial of IFN-gamma and IL-2 in patients with advanced cancer. Patients were treated three times weekly (Monday, Wednesday, and Friday) for 6 weeks with bolus injections of IL-2; each dose was preceded 2 h earlier by a s.c. injection of IFN-gamma. Patients were treated with IFN-gamma at 0.01, 0.05, 0.1, or 0.25 mg/m2/dose. At each IFN-gamma dose, cohorts of at least three patients were treated with IL-2 at 1, 2.5, 5.0, or 7.5 x 10(6) Cetus units/m2 dose. Patients with clinical responses continued therapy three times weekly, while those with stable disease at 6 weeks were then treated twice weekly. A total of 41 patients were treated, all with Eastern Cooperative Oncology Group performance status 0 or 1. All patients were evaluable for toxicity. Dose-limiting toxicities were cumulative fatigue and constitutional symptoms. One documented transmural myocardial infarct occurred. The maximally tolerated dose combination, based on analysis of IL-2 dose intensity, was 0.1 mg IFN-gamma/m2 and 7.5 x 10(6) Cetus units IL-2/m2 per dose. Two partial responses and two minor responses were observed. Treatment was not associated with dose-associated changes in peripheral blood lymphocyte phenotype, but there was a trend favoring IFN-gamma dose-associated rises in IL-2 induction of natural killer and LAK activity by treated patients' lymphocytes. Analysis of the cumulative effects of therapy on induction of natural killer and LAK activity by measurement of the median area under the curve of activation showed clear evidence of IFN-gamma and IL-2 dose-associated changes. The IL-2 dose effects on cell lysis were monotone, while the optimal IFN-gamma dose appeared to be 0.1 mg/m2/dose, with a bell-shaped dose-response curve described previously for other effects of this cytokine. Using this novel statistical method of evaluating the biological effects of treatment, the optimal biological dose was identical to the maximally tolerated dose.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phase I evaluation of combination therapy with interleukin 2 and gamma-interferon. 190 79


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