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 limited single-agent activity of cisplatin, its toxicity profile, and the inconvenience involved in hydrating patients has compelled researchers to investigate other treatments as possible alternative therapies in non-small cell lung cancer. More recently, interest has focused on the potential of nonplatinum combinations. Phase II studies show that the combination of docetaxel (Taxotere; Aventis, Antony, France) and gemcitabine is active in stage IIIB/IV non-small cell lung cancer not previously treated by chemotherapy. Response rates of up to 54% and a median survival time of 13 months have been reported. These data are comparable with the achievements of cisplatin-based combinations. A randomized phase II trial of docetaxel plus gemcitabine versus docetaxel plus cisplatin found that the two regimens were equally active in terms of response rate, median, and 1-year survival. However, the combination of docetaxel with gemcitabine produced significantly less neutropenia and nonhematologic toxicities. In combination, from 80% to 100% of the full single-agent gemcitabine and docetaxel doses can safely be administered once every 3 weeks. The combination of docetaxel plus vinorelbine is also active in non-small cell lung cancer and preliminary data suggest that this schedule with prophylactic filgrastim may optimize tolerability and dose intensity. In a phase II study using this approach, a confirmed response rate of 51% was obtained in 35 patients. At 12 months, the predicted median survival is 14 months and the predicted 1-year survival rate is 60%. Excessive lacrimation, fatigue, and onycholysis were cumulative toxicities. However, the incidence of mucositis and neuropathy was low with the combination of docetaxel and vinorelbine. Docetaxel combined with other new agents, particularly gemcitabine, may offer another useful alternative to cisplatin-based chemotherapy in patients with good performance status.
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PMID:Challenging the platinum combinations: docetaxel (Taxotere) combined with gemcitabine or vinorelbine in non-small cell lung cancer. 1128 20

Reiter's syndrome is an acute inflammatory arthritis with no standard treatment options for patients unresponsive to nonsteroidal antiinflammatory drugs (NSAID). In patients positive for human immunodeficiency virus (HIV), HIV-RNA levels have been correlated with elevated tumor necrosis factor-alpha (TNF-alpha) levels. We investigated the safety and activity of infliximab, an anti-TNF-alpha chimeric monoclonal antibody, in the treatment of an HIV positive patient with Reiter's refractory to NSAID therapy. A 41-year-old HIV positive man with Reiter's syndrome was treated with infliximab 300 mg intravenously at Weeks 0, 2, and 6 and then every 6 to 7 weeks thereafter. He presented with severe fatigue, pain, muscle wasting, synovitis of the elbows, wrists and knees, a scaly rash in the groin area, burning during urination, and severe onycholysis on all digits. Laboratory assessment revealed hemoglobin 7.8 g/dl, erythrocyte sedimentation rate (ESR) 152 mm/h, white blood cell count 5700 cells/mm3, and C-reactive protein (CRP) 65.7 mg/dl. HIV viral load on presentation was 1600 quantitative:ultrasensitive (Qn:US) copies/ml, decreased from a maximum of 428,000 Qn:US copies/ml at the start of antiretroviral therapy. After 6 months taking infliximab, all complaints resolved, nails regrew, and the rash cleared. CRP decreased to 0.8 mg/dl and ESR to 22 mm/h. During this 6 month period antiretroviral therapy remained unchanged, and the viral titer remained below 400 Qn:US copies/ml.
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PMID:Infliximab in the treatment of an HIV positive patient with Reiter's syndrome. 1256 4

Docetaxel was chosen for study in the combination chemotherapy of advanced non small-cell lung cancer on the basis of its reproducible high single-agent activity, novel mechanism of action, and relative lack of neurotoxicity. Preclinical and clinical data suggested schedule-dependent synergism with vinorelbine. Trials of docetaxel and vinorelbine have explored a variety of schedules. One approach has been to give docetaxel on day 1 of a 3-week cycle with vinorelbine on day 0 or days 1 and 5. Febrile neutropenia and non-neutropenic infections have been dose limiting, and low-dose intensity (8-13 mg/m2/week) of vinorelbine has been achieved. Our phase I study showed that docetaxel 60 mg/m2 and vinorelbine 45 mg/m2 every 2 weeks could be safely given with prophylactic filgrastim. In the ensuing phase II trial, we observed a 51% confirmed response rate in 35 patients (95% confidence interval [CI]: 34-68). With a median follow-up of 12 months, the predicted median and 1-year survivals are 14 months and 60%, respectively. Use of prophylactic filgrastim and the every-2-week schedule of administration allowed for single-agent dose intensity of both drugs to be given. Febrile neutropenia occurred in five patients and 5/384 cycles. Cumulative toxicities of excessive lacrimation, fatigue, and onycholysis were observed. More recently, a weekly schedule of administration for both drugs has been studied. Docetaxel and vinorelbine appear highly active together when given on an every-2-week schedule with prophylactic filgrastim, and the combination may offer one alter-native to cisplatin-based therapy. However, confirmatory phase II and III studies are needed. Certain cumulative toxicities (onycholysis, lacrimation) may limit the duration of therapy. Application of this regimen for a shorter period, such as in induction or postoperative settings, may provide optimal benefit while minimizing toxicity.
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PMID:Trials of vinorelbine and docetaxel in the treatment of advanced non small-cell lung cancer. 1472 39

Ixabepilone (Ix) (BMS-247550) is a potent member of a new class of microtubule-stabilizing cytotoxic agents known as epothilones. In pre-clinical studies, Ix has shown anticancer activity against several cancer types, including paclitaxel-resistant models, both in vitro and in vivo. The major toxicities associated with Ix are myelosuppression, sensory neuropathy and neutropenia. Other minor side-effects include asthenia/fatigue, stomatitis, anorexia, alopecia, skin reaction, hypersensitivity reactions and a fluid-retention syndrome. Although Ix is functionally correlated to taxanes, no previous evidence exists regarding Ix-related nail disorders. Here, we report a case of a 59-year-old woman treated with Ix at 40 mg/m2 day 1 q 21 days who, after 8 cycles of therapy, developed onycholysis and subungual hemorrhagic bullas in the fingernails.
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PMID:Nail disorders in a woman treated with ixabepilone for metastatic breast cancer. 1610 Nov 75

Psoriasis is a chronic, inflammatory disease affecting 1-3% of the world's population. Joints can be affected in up to 30% of patients. About one third of patients have either severe or moderate (involving more than 10% of body surface area) disease. Patients affected with extensive psoriasis have an impaired quality of life. Psoriasis has a large spectrum of clinical features and evolution, so no complete agreement on the classification of the clinical variants exists. Plaque psoriasis is the commonest form (more than 80% of affected patients). The course of plaque psoriasis varies. Spontaneous resolution is possible, but rarely occurs. Plaques tend to remain static or slowly enlarge. Flexural (inverse, intertriginous) psoriasis manifests with lesions thinner than those of plaque form with no or minimal scaling, and is localized in the skin folds. Guttate (eruptive) psoriasis has frequently a sudden onset and frequently appears abruptly after a bacterial or viral febrile episode of inflammation of the upper ways. Pustular and erythrodermic psoriasis are the most severe clinical variants. In the diffuse pustular form recurrent episodes of fever occur, followed by new outbreaks of pustules. Erythrodermic psoriasis corresponds to the generalized form of the disease. The entire skin is bright red and is covered by superficial scales. Fatigue, myalgia, shortness of breath, fever and chills may also occur. In sebopsoriasis (seborrheic dermatitis + psoriasis) the lesions tend to occur at the same sites as seborrheic dermatitis; greasy scales predominate, but silvery scales can be found in some areas. Nail psoriasis shows various features: nail pits; oil spots; subungual hyperkeratosis; onycholysis. Rare forms include psoriasis circinata, lip psoriasis and oral psoriasis. Differential diagnosis includes many other dermatological conditions.
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PMID:Clinical presentation of psoriasis. 1782 42

The limited single-agent activity of cisplatin, its toxicity profile, and the inconvenience involved in hydrating patients has compelled researchers to investigate other treatments as possible alternative therapies in non-small cell lung cancer. More recently, interest has focused on the potential of nonplatinum combinations. Phase II studies show that the combination of docetaxel (Taxotere; Aventis, Antony, France) and gemcitabine is active in stage IIIB/IV non-small cell lung cancer not previously treated by chemotherapy. Response rates of up to 54% and a median survival time of 13 months have been reported. These data are comparable with the achievements of cisplatin-based combinations. A randomized phase II trial of docetaxel plus gemcitabine versus docetaxel plus cisplatin found that the two regimens were equally active in terms of response rate, median, and 1-year survival. However, the combination of docetaxel with gemcitabine produced significantly less neutropenia and nonhematologic toxicities. In combination, from 80% to 100% of the full single-agent gemcitabine and docetaxel doses can safely be administered once every 3 weeks. The combination of docetaxel plus vinorelbine is also active in non-small cell lung cancer and preliminary data suggest that this schedule with prophylactic filgrastim may optimize tolerability and dose intensity. In a phase II study using this approach, a confirmed response rate of 51% was obtained in 35 patients. At 12 months, the predicted median survival is 14 months and the predicted 1-year survival rate is 60%. Excessive lacrimation, fatigue, and onycholysis were cumulative toxicities. However, the incidence of mucositis and neuropathy was low with the combination of docetaxel and vinorelbine. Docetaxel combined with other new agents, particularly gemcitabine, may offer another useful alternative to cisplatin-based chemotherapy in patients with good performance status.
 ...
PMID:Challenging the platinum combinations: Docetaxel (Taxotere) combined with gemcitabine or vinorelbine in non-small cell lung cancer. 2814 77