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)

Thalidomide has been reported to be effective in treating graft-versus-host disease, a condition with many clinical and pathological similarities to primary biliary cirrhosis. We performed a double-blind, placebo-controlled pilot study to assess the efficacy of thalidomide in 18 patients with biopsy-proven primary biliary cirrhosis (10 thalidomide, 8 placebo). Each patient was treated for 6 months and had a liver biopsy before and after treatment. Side effects, particularly sedation and fatigue, were more common on thalidomide and two patients were withdrawn from this group. There were no improvements in liver function tests or in liver histology, assessed morphometrically. A number of patients treated with thalidomide reported an improvement in pruritus. This study suggests that thalidomide is unlikely to be effective in altering the natural history of primary biliary cirrhosis.
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PMID:Thalidomide as therapy for primary biliary cirrhosis: a double-blind placebo controlled pilot study. 781 94

Although it is usually accepted that the pathogeny of HIV infection is related to the direct cytotoxic effect of the virus or indirectly by the invasion of T4 cells altering the T4/T8 ratio, clinical and serological and biochemical manifestations of the B cell polyclonal activation were described early in HIV infection epidemy. It is postulated that the central pathophysiologic mechanism in HIV infection is a high and inefficient production of interferon-gamma, genetically determined, leading to a production of autoantibodies that blocks the target organs even the immune system as well as a progressive interleukins levels increase, including tumor necrosis factor-alpha (TNF-alpha), responsible for many of the symptoms of these patients like fever, headache, fatigue, myalgia, hypotension, seizure and other neurological disorders, hematologic and hepatic disorders. Thalidomide reduces polyclonal hypergammaglobulinemia, that is associated with a clinical and laboratorial improvement, in a dose dependent manner as well as TNF-alpha levels. It seems that HIV infection is more a disease of abnormal host response triggered by HIV than an HIV disease.
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PMID:Autoimmunity in human immunodeficiency virus infection and the use of thalidomide. 809 May 35

Thalidomide is currently under investigation for its proposed value in treating a number of AIDS-related conditions. Banned in the 1960s because it was found to cause birth defects, thalidomide has been found to inhibit tumor necrosis factor (TNF), a cytokine associated with the development of aphthous ulcers, dementia, fevers, fatigue and wasting, as well as enhanced HIV replication. Development rights to use the drug are owned by Celgene, which calls the drug Synovir. Celgene is currently developing several new TNF inhibitors which are chemically analogous to thalidomide but which might be safer or more effective. Currently, at least 38 sites around the country are testing thalidomide for HIV-related ulcers, and six trial sites are testing for wasting syndrome. Thalidomide is in trials for the treatment of primary HIV infection at five sites. However, it is unclear whether thalidomide does more to curb HIV activity beyond inhibiting TNF. Thalidomide trials have been slow to recruit, therefore buyers clubs are working to make the drug available through their services.
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PMID:Thalidomide and HIV: several possible uses. 1136 2

In addition to immunomodulatory and cytokine-modulatory properties, thalidomide has antiangiogenic activity. It has been investigated in a number of cancers including multiple myeloma, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Its role has been best explored in myeloma, where, at daily doses of 100 to 800 mg, it is remarkably active, causing clinically meaningful responses in one-third of extensively pretreated patients and in over half of patients treated early in the course of the disease. It also acts synergistically with corticosteroids and chemotherapy in myeloma. Thalidomide produces improvement of cytopenias characteristic of myelodysplastic syndrome, resulting in the reduction or elimination of transfusion dependence in some patients. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high grade glioma and, in combination with irinotecan, in some patients with colon cancer. Thalidomide is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation and fatigue are common adverse effects seen in 75% of patients. Symptoms of peripheral neuropathy and skin rash are seen in 30%. A minority of patients experience bradycardia and thrombotic phenomena. Despite the high frequency of adverse effects, those severe enough to necessitate cessation of therapy are seen in only 10 to 15% of patients. A therapeutic trial of thalidomide should be considered in all patients with myeloma who are unresponsive to or relapse after standard therapy. In other malignant diseases, the most appropriate way to use the drug is in the setting of well designed clinical trials. In the absence of access to such studies, thalidomide could be considered singly or in combination with standard therapy in patients with no meaningful therapeutic options.
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PMID:Thalidomide in cancer: potential uses and limitations. 1143 82

Tumor angiogenesis is a critical factor in the growth and metastasis of most malignant neoplasms. Thalidomide (Thalomid), banned from clinical use in the 1960s because of severe teratogenicity, has been shown to possess antiangiogenic properties. A recent clinical trial of antiangiogenic therapy with thalidomide demonstrated significant activity in a group of patients with relapsed refractory myeloma. Although its mechanism of action remains unclear, several trials have since confirmed that thalidomide is active in 25% to 35% of patients with relapsed myeloma. As a result, thalidomide has reemerged in clinical practice and is now actively being studied in the treatment of several cancers. Major toxicities associated with the use of thalidomide include constipation, sedation, skin rash, fatigue, and peripheral neuropathy. This article summarizes the current status of thalidomide therapy in cancer.
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PMID:Current status of thalidomide in the treatment of cancer. 1149 88

New therapeutic alternatives are needed to improve outcomes in patients with androgen-independent prostate cancer (AIPC). For several years, researchers at the National Cancer Institute have been interested in elucidating the importance of angiogenesis in the pathogenesis of prostate cancer and in identifying inhibitors of this process. Thalidomide has been shown to inhibit the ability of tumors to recruit new blood vessels. In a recent phase II trial of thalidomide in AIPC, 28% of patients achieved a prostate-specific antigen (PSA) decrease of >40%. The taxane docetaxel also produces PSA and measurable disease responses when used as monotherapy or as a component of combination chemotherapy for AIPC. Thus, based on the single-agent activity of thalidomide and docetaxel, we initiated a randomized phase II study of weekly docetaxel with or without thalidomide, 200 mg at bedtime, in patients with chemotherapy-naive metastatic AIPC. Docetaxel, 30 mg/m(2) intravenously, was administered every 7 days for 3 weeks, followed by a 1-week rest period. Both regimens have been well tolerated among the first 59 treated patients, with a near absence of grade (3/4) myelosuppression. Fatigue, hyperglycemia, and pulmonary toxicity were seen in both groups. Thrombotic events have been seen in the combination arm. Thirty-five percent (6 of 17) of the patients receiving docetaxel alone and 53% (19 of 36) of those receiving docetaxel and thalidomide have had a PSA decrease of at least 50%. Combining a cytotoxic agent with an angiogenesis inhibitor is a promising area of investigation for prostate cancer management.
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PMID:A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgen-independent prostate cancer. 1168 31

Treatment options and prognosis remains poor for patients with recurrent glioblastoma multiforme. These tumors are highly vascularised and over express angiogenic factors such as vascular endothelial growth factor and may potentially be responsive to antiangiogenic therapies. We present the results of a phase II trial of Thalidomide, an antiangiogenic agent, in the treatment of recurrent glioblastoma multiforme. Patients were treated with 100 mg/day of Thalidomide, increased at weekly intervals by 100 mg to a maximum tolerated dose of 500 mg/d. Forty-two patients were enrolled, with 38 patients being assessable for response and 39 for toxicity. Two patients (5%) achieved a partial response and 16 (42%) had stable disease. The median survival was 31 weeks and the 1-year survival was 35%. Patients who had a partial response or stable disease had either a stabilisation or improvement in quality of life scores or performance status. Overall Thalidomide was well tolerated with no grade 4 toxicities and no treatment related deaths. The median maximum tolerated dose was 300 mg/day. The most common toxicity was fatigue to which patients developed tachyphylaxis. There was no correlation demonstrated with plasma vascular endothelial growth factor levels and response or survival. Thalidomide is a well-tolerated drug that may have some activity in the treatment of recurrent glioblastoma. Optimum dosing with antiangiogenic agents is currently under investigation. Chronic low dose therapy may be required to see conventional responses or improvements in time to progression. The dose required to achieve optimal biological impact may be better defined once we have established reliable surrogate endpoints.
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PMID:Phase II study of thalidomide in the treatment of recurrent glioblastoma multiforme. 1176 20

Thalidomide has immunomodulatory and anti-angiogenic properties which may underlie its activity in cancer. After its success in myeloma, it has been investigated in other plasma cell dyscrasias, myelodysplastic syndromes, gliomas, Kaposi's sarcoma, renal cell carcinoma, advanced breast cancer, and colon cancer. Thalidomide causes responses in 30-50% of myeloma patients as a single agent, and acts synergistically with corticosteroids and chemotherapy. Thalidomide results in the reduction or elimination of transfusion-dependence in some patients with myelodysplastic syndrome. Responses have also been seen in one-third of patients with Kaposi's sarcoma, in a small proportion of patients with renal cell carcinoma and high-grade glioma, and in some patients with colon cancer in combination with irinotecan. The drug is being investigated currently in a number of clinical trials for cancer. Drowsiness, constipation, and fatigue are common side effects, whereas peripheral neuropathy and skin rash are seen in one-third. A minority of patients experience bradycardia. Thrombotic phenomena are especially common when thalidomide is combined with chemotherapy. Adverse effects severe enough to necessitate cessation of therapy are seen in around 20% of patients. A therapeutic trial of thalidomide is essential in all patients with relapsed or refractory myeloma. In other cancers, the best way to use the drug is in the setting of clinical trials. In the absence of access to studies or alternative therapeutic options, thalidomide could be considered singly or in combination with standard therapy.
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PMID:Thalidomide in cancer. 1190 8

Thalidomide--banned from clinical use in the 1960s because of severe teratogenicity--is now back in clinical practice as an effective agent in the treatment of relapsed and refractory multiple myeloma. Several clinical trials have determined that thalidomide is active in 25-35% of patients with relapsed myeloma. The role of thalidomide in early-stage myeloma is being actively investigated. Thalidomide has antiangiogenic and immunomodulatory properties and is an effective inhibitor of TNF-alpha. However, the mechanism of its action in myeloma remains unclear. Major toxicities of thalidomide include constipation, sedation, skin rash, fatigue and peripheral neuropathy. This paper summarizes the current status of thalidomide in multiple myeloma.
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PMID:Thalidomide in the treatment of multiple myeloma. 1211 24

We conducted a nonrandomized prospective phase II study of thalidomide in anemic patients with myelofibrosis with myeloid metaplasia (MMM), with or without preceding polycythemia vera or essential thrombocythemia, with a primary aim to improve anemia. Thalidomide was given in escalating doses with a target dose of 800 mg daily, but the median dose of thalidomide that was actually tolerated was 400 mg daily. Fifteen patients were entered into the study and 14 were evaluable for response. Five of 14 (36%) patients discontinued thalidomide before 3 mo because of side effects, and none of these five patients had a response at the time when thalidomide was stopped. When evaluated after 3 mo of therapy, none of the remaining nine patients exhibited a discernible clinical response. Three patients showed progressive disease defined as > 50% increase in the need for red cell transfusions. Treatment was poorly tolerated, with all patients reporting side effects of thalidomide, the most prominent being fatigue documented in 80% of patients. Two patients died while on study, one from acute myelogenous leukemia and one from pneumonia. We conclude that thalidomide given in doses employed in the treatment of multiple myeloma gives no clinically relevant hematological effects in advanced MMM and is hampered by a very high incidence of side effects.
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PMID:Negligible clinical effects of thalidomide in patients with myelofibrosis with myeloid metaplasia. 1218 Apr 84


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