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)

We performed a Phase I assessment of recombinant human tumor necrosis factor (rTNF-alpha) in 27 patients with advanced solid neoplasms. Therapy consisted of a 30-minute intravenous (IV) infusion on days 1 through 5, every 2 to 3 weeks. Daily doses ranged from 5 micrograms/m2 to 200 micrograms/m2. Dose-limiting sequelae were hypotension, rigors, and phlebitis. Transient fatigue and fever (median, 38 degrees C) were not clearly dose-related between 5 micrograms/m2/d and 150 micrograms/m2/d. Other reversible complications in three patients included transient leukopenia (leukocyte count, 1.3, 1.2 X 10(3)/microliters in two patients) at a dose of 5 micrograms/m2/d and 150 micrograms/m2/d, respectively; and thrombocytopenia (leukocyte count, 73 X 10(3)/microliters) at 10 micrograms/m2/d. Among 22 patients with initial and subsequent differential counts, the median number of eosinophils at the commencement of therapy was 182 cells/microliters compared with a subsequent median of 462 cells/microliters. We also detected hypertriglyceridemia in all patients. The median baseline increased from 93 mg/dl (range, 56 to 219 mg/dl) to 203 mg/dl (range, 94 to 454 mg/dl). From our experience, a clinically manageable outpatient regimen for Phase II trials consists of rTNF-alpha (150 micrograms/m2) followed by a 1-hour IV infusion of 500 ml of normal saline to abrogate hypotension daily for 5 days every 2 weeks for four cycles, then every 3 weeks thereafter to facilitate recovery from constitutional sequelae.
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PMID:A phase I clinical trial of recombinant human tumor necrosis factor. 319 49

Nine patients with metastatic breast cancer received 30 x 10(6) I.U. of Interferon - Betaser (Betaseron) intravenously daily times five for two consecutive weeks followed by a two week rest period. Only one patient received more than one such cycle of Betaseron. The drug was well tolerated in eight of these patients. One patient, with liver metastases and liver dysfunction, developed hepatic decompensation during therapy. Toxicity consisted of anorexia, chills, fever, fatigue and nausea with an occasional patient having emesis. One patient developed severe thrombocytopenia, two, significant leukopenia and nine, mild elevations of serum transaminase. Two patients developed beta interferon binding antibodies but none developed neutralizing antibodies. No anti-tumor responses were seen and disease progression occurred rapidly during the four week cycle in eight of nine patients.
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PMID:Phase II trial of recombinant beta (IFN-betaser) interferon in the treatment of metastatic breast cancer. 319 87

From 1977 to 1982, 62 patients with various advanced malignant solid tumors were treated by HD-MTX-CFR therapy and totally 129 courses were given. Majority of the patients suffered from malignant lymphoma (10), osteogenic sarcoma (11), lung cancer (16), esophageal cancer (3), breast cancer (3) and malignant melanoma (4). All were confirmed by cytology or pathology except one primary liver cancer. There were clinically measurable lesions in 59 patients for evaluation of the treatment, and 3 osteogenic sarcoma patients without metastasis were given a postoperative adjuvant chemotherapy. 33 out of 62 had received chemotherapy and/or radiotherapy before. Dose of MTX ranged from 2 to 3 gm per course in most patients and dose of CF, from 9 to 12 mg every 6 hours for 3 days. 2 (3.4%) patients achieved complete remission (1 osteogenic sarcoma and 1 malignant lymphoma) and 8 (13.6%), partial remission (1 osteogenic sarcoma, 5 malignant lymphoma, 1 esophageal cancer and 1 breast cancer) with a total response rate of 15.9%. No response was observed in all 16 lung cancers. The main side effects of HD-MTX-CFR therapy were leukopenia, thrombocytopenia, elevation of SGPT, nausea, vomiting, mucositis, skin rash, fever and fatigue. All patients were followed more than 3 years. 4 patients are still alive (9, 9, 4 and 7 years, respectively), including 3 osteogenic sarcoma patients who received postoperative adjuvant chemotherapy and 1 mycosis fungoides.
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PMID:[High-dose methotrexate with citrovorum factor rescue (HD-MTX-CFR) in the treatment of malignant solid tumors--clinical analysis of 62 patients]. 326 85

Twenty-four patients with advanced and therapy-resistant ovarian carcinoma were treated with escalating daily doses of human leukocyte interferon (IFN). Doses ranged from 3 X 10(6) to 27 X 10(6) IU/day. Fatigue, fever, thrombocytopenia, and leukopenia were the limiting factors in the escalation of doses. Of nine patients treated for at least 2 months, there were two patients with partial remissions and six with stable disease. Ascites production present in four patients became reduced in three. The level of 2',5'-oligoadenylate synthetase in peripheral blood lymphocytes increased following initiation of IFN therapy. We conclude that IFN-alpha can exert an antitumor effect in some patients with ovarian carcinoma that have previously failed on other therapy regimens.
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PMID:A phase II study on escalating interferon doses in advanced ovarian carcinoma. 327 73

Recombinant human tumor necrosis factor (rH-TNF) is a cytotoxic monokine with pleiotropic effects. A phase I trial of rH-TNF was initiated using a five-day continuous intravenous (IV) infusion repeated every 28 days. Thirty-eight courses of therapy were administered to 19 patients. The starting dose was 5 X 10(4) U/m2/d, with escalations to 1.0 X 10(5), 2.0 X 10(5), 2.4 X 10(5), and 3.0 X 10(5) U/m2/d. Systemic side effects, including fever, chills, hypotension, fatigue, anorexia, and headaches, were mild and self-limiting. At the maximum tolerated dose of 3.0 X 10(5) U/m2/d, dose-limiting hematologic toxicity was manifested by transient thrombocytopenia and leukopenia. Elevated bilirubin levels were also seen at the higher dose levels. Lipoprotein analysis demonstrated that the five-day treatment with rH-TNF was associated with decreases in high-density lipoproteins, as well as increases in triglycerides and very-low-density lipoproteins. Pharmacokinetic studies using an enzyme-linked immunosorbent assay (ELISA) test indicated plasma rH-TNF levels less than 0.2 U/mL. The recommended phase II dose of rH-TNF administered as a five-day continuous infusion is 2.4 X 10(5) U/m2/d.
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PMID:Recombinant human tumor necrosis factor administered as a five-day continuous infusion in cancer patients: phase I toxicity and effects on lipid metabolism. 333 98

In order to further extend the duration of remission induced by high-dose CAF therapy, maintenance therapies based on long-term oral administration of cyclophosphamide and fluorouracil (CF) were applied for patients with advanced and recurrent breast cancer. The duration of remission was compared by the envelope method among the basic therapy (Arm I), Arm I plus intermittent administration of adriamycin (Arm II) and Arm I plus tamoxifen from the start of high-dose CAF therapy (Arm III). The response rate of 163 evaluable patients in 30 institutes was 42.1% (27/57) and 44.4% (25/54) for Arm I and Arm II (CAF therapy). The rate for Arm III (CAF therapy) was 61.5% (32/52), a little higher than that for the other two. As side effects due to the induction therapy, alopecia, fatigue, anorexia, nausea and vomiting, and leukopenia were observed in a relatively high proportion of patients. Mean values of CR duration, PR duration and the whole duration of remission in responding patients were 14.0 approximately 21.5 weeks, 24.0 approximately 32.2 weeks and 28.0 approximately 42.6 weeks, respectively, without any significant difference among the three groups given different maintenance therapies. The mean values of survival duration in responding patients were 27.1, 22.0 and 17.2 months, respectively for Arm I, Arm II and Arm III no significant difference being recognized in this point, either.
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PMID:[Clinical evaluation of adriamycin in advanced and recurrent breast cancer (No. 4)--Joint study by 30 institutes on the duration of remission using various maintenance therapies in patients treated with CAF. Clinical Study Group of Adriamycin for Breast Cancer in Japan]. 338 38

A phase II study of epirubicin, a new anthracycline derivative, was performed in 23 patients with advanced gastric cancer. Epirubicin was administered intravenously at a dose of 20-30 mg/m2/day for two or three consecutive days every two or three weeks. Sixteen cases were evaluable and there were two partial responses and one minor response. Overall response rate (more than PR) was 12.5% (2/16). Leukopenia (less than 4,000/mm3) and anemia (less than 11.0 g/dl) were observed in 71.4% and 69.2% of patients, respectively. No thrombocytopenia was observed. Other toxicities were alopecia (71.4%), nausea and vomiting (42.9%), anorexia (25.0%), stomatitis (12.5%), fatigue (12.5%), fever (6.3%) and tachycardia (6.3%), but these effects were relatively mild in most cases.
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PMID:[Phase II study of epirubicin on gastric cancer--a cooperative study of the Tokai Cancer Chemotherapy Group]. 346 May 30

This double-blind, placebo-controlled study evaluated the efficacy and safety of sc administered recombinant alpha 2 interferon (IFN-alpha 2) in the suppression of frequently recurrent genital herpes simplex virus (HSV) infection. Seventy-six otherwise healthy subjects who had eight or more recurrences during the preceding year received 1 X 10(6) IU of IFN-alpha 2, 3 X 10(6) IU of IFN-alpha 2, or placebo three times per week for 12 weeks. Recipients of the higher dose of IFN-alpha 2, had fewer outbreaks during the study (2 vs. 3), a shorter period of viral shedding (2 vs. 4 days), less itching (1 vs. 3 days), and a faster healing time (6 vs. 8 days). The lower dose of IFN-alpha 2 was not effective. Significant side effects (fever, malaise, myalgia, fatigue, and arthralgia) occurred after the first injection of 3 X 10(6) IU of IFN-alpha 2 in 91% of the subjects, but subsequent injections produced only mild and intermittent side effects that were well tolerated. Mild leukopenia was noted in subjects treated with IFN-alpha 2. Treatment with IFN-alpha 2 resulted in moderate suppression and decreased duration of recurrent genital HSV infection in patients with frequent recurrences.
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PMID:Suppression of recurrent genital herpes simplex virus infection with recombinant alpha 2 interferon. 352 95

Current therapy for condylomata acuminata (genital warts) is not consistently effective. Therefore, we conducted a randomized, double-blind trial to compare interferon alpha-2b with placebo in the treatment of this disorder. Our rationale was that interferon has both antiproliferative and antiviral properties. The placebo or interferon (1 X 10(6) IU) was injected directly into one to three warts three times weekly for three weeks. The injections were well tolerated by both groups of patients. The side effects of fever, chills, myalgia, headache, fatigue, and leukopenia occurred more commonly in the interferon group than in the placebo group, but such effects rarely disrupted daily routines. Only 13 of 296 patients (4 percent) discontinued therapy because of side effects (11 in the interferon group and 2 in the placebo group). Twenty-six other patients were excluded from analysis because of a loss to follow-up or other deviations from protocol, thus leaving 257 patients in the final evaluation. At one week after the completion of therapy, interferon had produced a large and significantly greater reduction in mean wart area (a 62.4 percent decrease), as compared with placebo (a 1.2 percent increase in mean area) (P less than 0.001). At the conclusion of the study (13 weeks after the completion of therapy), the mean wart area was still decreased 39.9 percent below the initial size in the interferon group, whereas it had increased by 46 percent over base-line measurements in the placebo group (P less than 0.001). At the same time, all treated warts had completely cleared in 36 percent of the interferon recipients and in 17 percent of the placebo recipients (P less than 0.001), whereas treated warts progressed in 13 percent of the interferon recipients and in 50 percent of the placebo recipients (P less than 0.001). We conclude that injection of interferon alpha-2b directly into genital warts appears to be an effective and fairly well-tolerated form of therapy.
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PMID:Interferon therapy for condylomata acuminata. 353 60

Nine patients with hormone-resistant prostate carcinoma were treated with subcutaneous injection of recombinant human interferon-alpha 2 (rHuIFN-alpha 2), 5-10 X 10(6) U/m2, three times a week. One patient had a mixed clinical response with reduction of bone pain. The study was closed due to intolerable grade III and IV toxicities including weight loss (8/9), fatigue/malaise (7/9), central nervous system toxicity (4/9), leukopenia (3/9), and uncontrollable nausea and vomiting (2/9). These toxicities resulted in deterioration of performance status. It is concluded that rHuIFN-alpha 2, at least at the dose and schedule studied, should not be used for the treatment of patients with hormone-resistant prostate carcinoma.
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PMID:Toxicities of human recombinant interferon-alpha 2 in patients with advanced prostate carcinoma. 357 90


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