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)

The combination of cisplatin 100 mg/m2 every 3 weeks and mitoguazone 500 mg/m2 every week with dose escalation was administered as a 9-week induction regimen to 27 patients with previously untreated Stage III or IV squamous cell carcinoma of the head and neck. This was followed by full-course radiation therapy for unresectable patients or surgery and postoperative radiation therapy for those with resectable disease. Sixteen patients had bulky unresectable disease, and ten were candidates for curative resection at study entry. Of 26 patients evaluable for response to chemotherapy, there were seven complete responses (CR) (five of six pathologically confirmed) and ten partial responses (PR) (65% CR + PR). Toxicity was generally mild with Grade 3 or 4 nausea and vomiting occurring in 15% and diarrhea in 12%. Nineteen percent of the patients developed transient nephrotoxicity (serum creatinine greater than 2), 62% anemia (hemoglobin decrease greater than 2 g/dl), 23% leukopenia (leukocyte count less than 3500 cells/microliters) and 8% thrombocytopenia (platelets less than 50,000 cells/microliters). Anorexia, fatigue, and weight loss occurred in nearly all patients. The median survival time of all patients was 17.5 months; complete responders, 43 months; partial responders, 16 months; and nonresponders, 9 months (P = 0.0025). In a multivariate analysis of stage, primary site, resectability status, response to chemotherapy, and local treatment (surgery plus radiation versus radiation), complete response was the only statistically significant covariate for survival. In Phase II single agent trials, mitoguazone has been shown to have a 15% response rate in head and neck cancer and cisplatin, a 30% to 40% response rate (less than 10% CR). Thus, our results, both complete and overall response rates, were higher than would be expected from either drug alone. A possible mechanism for this high response rate may be mitoguazone-induced cell synchronization. In vitro studies demonstrate the accumulation of tumor cells exposed to mitoguazone in S- and G2-phases of the cell cycle. These results would support further evaluation of mitoguazone in combination to explore the theoretical potentiation of antitumor effects by sequencing with cycle-specific agents.
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PMID:Cisplatin and mitoguazone. An induction chemotherapy regimen in advanced head and neck cancer. 317 46

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

Confirmation of a causal relationship between hemolytic-uremic syndrome (HUS) and verotoxin-producing Escherichia coli (VTEC) infection is provided by the case of a 22-year-old West German woman. The patient presented with fatigue, nausea, and headache. Ultrasonography revealed enlarged kidneys, and laboratory investigations showed uremia, hemolytic anemia, lactate dehydrogenase, haptoglobin below the detection limit, and thrombocytopenia. She received hemodialysis and drug treatment (heparin, dopamine, and furosemide). To investigate the kinetics of the humoral response to verotoxin, the patient was followed for 3 months. Fecal specimens on day 23 yielded E coli serotype 0111:NM, and stool filtrates on days 16 and 23 showed highly cytotoxic activity for HeLa cells. While the patient's initial serum showed a high IgM immune response against purified Shiga toxin, there was a steady decline in IgM and steady increase in IgG antibodies over the ensuing 3 months. These findings are suggestive of a recent infection by a verotoxin-producing organism. This is the 1st reported case of VTEC-associated HUS with e coli 0111 infection in an adult, and the patient's 4-year history of oral contraceptives (OCs)--ethinyl estradiol and chlormadinoneacetate--is considered to be of etiologic significance. The diminished antibody coating of bacteria in the urinary tract of OC users may have facilitated invasion of verotoxin across the mucosal barrier in this patient. Severe hypertension has been reported previously in OC users with HUS. It is speculated that verotoxin may trigger HUS in longterm OC users, initiating vasoconstriction and microangiopathic hemolysis.
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PMID:Hemolytic-uremic syndrome associated with an infection by verotoxin producing Escherichia coli 0111 in a woman on oral contraceptives. 328 32

A 20-year-old white male was initially suspected clinically and pathologically of having an acute lymphoblastic leukemic process because of fatigue, severe anemia, thrombocytopenia, a leuko-erythroblastic peripheral blood picture, and a diffusely infiltrated bone marrow. Subsequent review of the bone marrow material indicated cytologic features consistent with either an embryonal, undifferentiated small cell mesenchymal malignancy or reticulo-endothelial malignancy. Ultimately, the electron microscopic (EM) study of the tumor proved to be diagnostic of rhabdomyosarcoma. An extensive search for a primary site of rhabdomyosarcoma did not show any lesion, although the genitourinary region was clinically suspected. The clinical course was a rapidly downhill one with extensive bone and CNS involvement. The patient died 5 months later. An autopsy permit was not obtained. This case emphasizes the occasional tendency of rhabdomyosarcoma to masquerade as a hematopoietic malignancy at the time of presentation and the usefulness of EM study in confirming a diagnosis.
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PMID:Systemic rhabdomyosarcoma presenting as leukemia: case report with ultrastructural study and reviews. 330 41

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

We report a phase I clinical investigation of 30-minute and four-hour intravenous (IV) infusions of recombinant tumor necrosis factor (rTNF)-alpha. Thirty-nine patients with disseminated cancer received escalating doses of rTNF-alpha for five consecutive days every 2 weeks for a total duration of 8 weeks. Dose escalations followed a modified Fibonacci scale with a minimum of four patients entered at each dose level: 5, 10, 25, 50, 75, 100, 150, 200, and 250 micrograms/m2/d. Toxicities consisted mainly of constitutional symptoms including fever, chills, headache, and fatigue, increasing in severity with dose escalation. No significant differences in dose-limiting toxicities were seen between the two rates of IV infusion. The maximum tolerated dose (MTD) was 200 micrograms/m2 with dose limiting toxicity being constitutional symptoms and hypotension. Hematologic changes included median decrease in both granulocyte and platelet counts of 38% and 41%, respectively (range, 16% to 85%), although clinically significant granulocytopenia and thrombocytopenia were not observed. Hematological parameters returned to baseline within 72 hours after rTNF-alpha was stopped. rTNF-alpha induced changes in lipid metabolism were manifested by median fasting triglyceride elevations above baseline (median, 103 micrograms/dL) of 157% (range, 16% to 389%) after five days of therapy with doses greater than 75 micrograms/m2, associated with a median increase in very-low-density lipoprotein (VLDL) of 80%. Serum rTNF peak levels exceeding 10 ng/mL were observed 30 minutes following rTNF-alpha infusions at MTD dose. Twelve of 34 patients had no change in their evaluable disease for a median duration of 18 weeks (range, 8 to 30 weeks), and 22 patients showed progressive disease. This study forms the framework for phase II trials of IV administered rTNF-alpha.
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PMID:A phase I trial of intravenously-administered recombinant tumor necrosis factor-alpha in cancer patients. 341 44

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


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