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)

alpha-Interferon has antitumor activity in a variety of malignancies but is frequently associated with unacceptable toxic side-effects. The routine use of agents potentially capable of reducing these side-effects has not been recommended out of concern for possible reductions in the therapeutic activity of interferon. We conducted a prospective randomized trial of alpha-interferon given with or without indomethacin to patients with malignant melanoma to determine what effect, if any, indomethacin might have on the toxic, immunomodulatory, and therapeutic properties of interferon in this disease. 53 patients were stratified according to performance status and randomized to receive alpha 2b-interferon, 20 million units per m2 i.v., 5 days per week for 4 weeks followed by 10 million units per m2 s.c. three times per week, either with or without indomethacin, 25 mg orally three times a day. The overall major response rate was 13% (three complete responders and three partial responders among 47 evaluable patients) and was the same on both arms. The mean maximal temperature elevation induced by interferon was significantly reduced (from 102.1 to 100.7, P = 0.0002) by indomethacin, but the incidence and severity of interferon-related fatigue, reduction in performance status, headache, depression, confusion, elevations in liver function tests, and myelosuppression were no different in either arm of the study. Indomethacin did not reduce the frequency of dose reductions for toxic side-effects and did not permit the administration of higher interferon doses. Peripheral blood natural killer activity was significantly enhanced in patients during maintenance therapy whether or not they received indomethacin. Indomethacin appeared to inhibit augmentation of natural killer activity during high dose induction therapy. Immunological changes did not correlate with response status. We conclude that indomethacin can reduce the fever associated with interferon therapy in patients with malignant melanoma without interfering with its therapeutic or chronic immunomodulatory activities. Since fever is rarely the dose-limiting toxicity of interferon, indomethacin is of marginal benefit to patients with malignant melanoma receiving interferon at the doses outlined in this study.
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PMID:Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma. 264 94

Eicosanoids may be important factors for tumor cell proliferation, metastatic formation, and development of cancer cachexia. The present study has evaluated the effect of anti-inflammatory treatment on tumor progression in clinical cancer. Patients (n = 135) with insidious or overt malnutrition due to generalized malignancy (various kinds of solid tumors) and an expected survival of more than 6 months were randomized by a computer-based algorithm to receive placebo, prednisolone (10 mg twice daily), or indomethacin (50 mg twice daily) p.o. until death. Patient groups were stratified in the randomization procedure for sex, tumor type, stage, nutritional state, and previous tumor treatment, and biochemical, physiological, and some functional variables (Karnowsky index, fatigue and pain score). A majority of these variables was then registered during the follow-up. Indomethacin and prednisolone treatment maintained Karnowsky index, while placebo-treated patients experienced a decreased index. Indomethacin-treated patients suffered less pain and consumed less additional analgetics compared to the other patient groups. Indomethacin prolonged mean survival compared to placebo-treated patients from 250 +/- 28 days to 510 +/- 28 days (P < 0.05). Survival analysis on observations from all patients treated with either indomethacin or prednisolone demonstrated a significantly prolonged survival by anti-inflammatory treatment compared to placebo treatment (log rank, P < 0.03). The results suggest that not only may prostaglandin synthesis inhibition offer palliative support to patients with solid advanced cancer, but it may also impact on pathways that ultimately determine outcome.
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PMID:Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. 792 4

Combination therapy with docetaxel, cisplatin, and 5-FU has been shown to increase time to progression (TTP) and overall survival (OS) for patients with advanced gastric cancer; this regimen is limited by significant toxicity, including complicated neutropenia. This study was designed to incorporate docetaxel into a tolerable biweekly (once every 2 weeks) oxaliplatin-based chemotherapy regimen. Patients with measurable advanced and metastatic gastric or gastroesophageal cancer, aged >18 years, and with ECOG two or less, received oxaliplatin 85 mg/m(2), docetaxel 50 mg/m(2) on day 1, leucovorin 200 mg/m(2) on days 1 and 2, and 5-FU 1,200 mg/m(2) 24-h infusion on days 1 and 2 of every 2-week cycle. Toxic effects were graded according to NCI-CTC version 3. Responses were classified according to World Health Organization criteria. Fifty patients were included, 47 assessed for efficacy and toxicity. Median age was 55 years. The majority had metastatic disease (72 %). The over all response was observed in 55.3 % patients. Median TTP and OS were 6 and 10 months, respectively. Grade 3 or 4 hematological toxic effects were included neutropenia, leukopenia, and thrombocytopenia observed in 21 (44.7 %), 12 (25.5 %), and 1 (2.1 %) patients, respectively. Non-hematological were diarrhea (14.9 %), fatigue (12.7 %), and peripheral neuropathy (8.5 %). Complicated neutropenia (febrile neutropenia associated with infection) was observed in one (2.1 %) patient only. Biweekly FLOT regimen has tolerable toxicity, and efficacy in line with that of DCF protocol. The FLOT regimen needs more evaluation to be considered as alternative to DCF.
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PMID:The safety and efficacy of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) combination in the front-line treatment for patients with advanced gastric or gastroesophageal adenocarcinoma: phase II trial. 2330 58

Bartter-Gitelman syndromes are rare inherited autosomal recessive salt-losing tubulopathies characterized by severe and chronic hypokalemia associated with metabolic alkalosis and secondary hyperaldosteronism. Bartter syndrome results from a furosemide-like defect in sodium reabsorption in the Henle's loop leading to hypercalciuria and defect in urinary concentration capacity. The antenatal Bartter syndrome is defined by polyhydramnios and an infantile polyuria with severe dehydration whereas classic Bartter syndrome appears during childhood or adulthood. Gitelman syndrome is a thiazide-like salt-losing tubulopathy. It is associated with hypomagnesemia, hypocalciuria without defect in urinary concentration capacity. The diagnosis is most often made in adolescents or adults. Clinical symptoms include tetany, delay in the height-weight growth curves, chronic tiredness, muscle weakness, myalgia and vertigo. Nephrocalcinosis in Bartter syndrome could lead to chronic kidney disease. Antenatal Bartter syndrome requires hospitalization in intensive care unit to manage the severe newborn dehydration. Chondrocalcinosis is the major complication in the Gitelman syndrome. The corner stones of treatment is the fluid and electrolyte management Bartter and Gitelman syndromes need lifelong oral supplementations of potassium, salt (Bartter) and magnesium (Gitelman). Indomethacin is efficient to reduce water and electrolyte loss in Bartter. In Gitelman, potassium-sparing diuretics may be helping for severe hypokaliemia but they will reinforce hypovolemia.
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PMID:[Bartter-Gitelman syndromes]. 3262 51