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)

A seventy-five-year-old female with general fatigue, high fever and anemia was admitted. Her chest X-ray film revealed pneumonia. She was diagnosed as RAEB-t with the normal karyotype by peripheral blood film and bone marrow aspiration; 125 micrograms/ml of G-CSF was administered s.c. daily in order to increase neutrophil count because of the prolongation of pneumonia. Her blast cells in both peripheral blood and bone marrow showed a remarkable increase by G-CSF. After the cessation of G-CSF administration, blast cells decreased rapidly, and neutrophil count in the peripheral blood increased. Her pneumonia was then cured. After 5 months of stable hematological state, 60% of her bone marrow cells became occupied by blast cells again. So 2 consecutive courses of 14 days p.o. administration of 1,200 mg MST-16/day were tried. Three months after the first MST-16 trial, her bone marrow showed complete remission (CR) which lasted about 4 months. But she died of sepsis after the first relapse. Her bone marrow in CR still revealed several features of dyspoiesis.
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PMID:[A case of RAEB-t treated by G-CSF showing complete remission after MST-16 treatment for subsequent reversible leukemia]. 171 93

The genes for a number of growth factors that stimulate human hematopoietic and lymphoid cells in vitro have recently been cloned and recombinant molecules provided for clinical trials. For three of these (erythropoietin, G-CSF, and GM-CSF), phase I and II studies have been completed and promising results have been obtained. Of particular relevance to the field of bone marrow transplantation (BMT) has been the finding that G-CSF and GM-CSF could shorten the period of neutropenia in patients treated with chemotherapy, including regimens requiring BMT support. Doses of up to 240 micrograms/m2 of GM-CSF have been well tolerated and have increased the peripheral blood neutrophil count in a dose-dependent manner. At higher doses, eosinophils and monocytes were also increased. A continuous infusion over at least 2 h was found to be superior to bolus administration in terms of both efficacy and reduced side effects. These have usually been mild, but bone pain, headache, fatigue and elevated temperature have been encountered. The rise in neutrophil numbers shortly after initiating treatment with GM-CSF is probably due to neutrophil demargination. After a few days increased bone marrow cellularity has also been noted. In addition to these effects on cell numbers, enhancement of granulocyte and monocyte functions has been documented. However, a major concern with the use of G-CSF and GM-CSF in cancer patients, particularly those with hematopoietic malignancies, is the potential of these molecules to stimulate malignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony stimulating factors. 245 88

We investigated a dose-escalation effect of G-CSF (5, 10, and 15 micrograms/kg) on mobilization of committed and primitive hemopoietic progenitor cells, including CFU-GM, BFU-E, and long-term culture-initiating cells (LTC-IC) in addition to CD34+ cells and yields of progenitor cells in PBSC harvests obtained by leukapheresis of healthy adult donors. Results indicate that the mobilization of these progenitor cells is both dose and time dependent. Despite the very small number of healthy donors studied, it is estimated from our data that a sufficient number of CD34+ cells for allogeneic PBSC transplant (PBSCT) could be collected using a 5 day administration of 10 micrograms/kg of G-CSF to normal adult donors. Adverse effects include general fatigue and bone pain in most of the donors and fever and headache in some. These symptoms were well tolerated in most instances. Laboratory test abnormalities, including transient thrombocytopenia, increased platelet aggregation, and increased serum levels of some liver enzymes, were induced by G-CSF administration, but all were reversible within a short time. These observations suggest that hemopoietic stem cells for allogeneic PBSCT can be mobilized by short-term administration of a relatively high-dose G-CSF.
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PMID:G-CSF-induced mobilization of peripheral blood stem cells from healthy adults for allogeneic transplantation. 864 83

We treated fifteen patients with recurrent breast cancer by a combination of mitoxantrone (8 mg/m i.v., day 1), vincristine (1.2 mg/m i.v., day 1), doxifluridine (800 mg/body po, everyday) and prednisolone (30 mg/body po, day 1-7). Cycles were repeated every 3 weeks and all patients received more than 2 cycles. A response to treatment was observed in 9 of 15 evaluable patients (60.0%) with 4 complete remissions and 5 partial remissions. Eight patients were previously exposed to anthracyclines. In 5 of 7 cases with no previous chemotherapy, treatment was effective, and in 4 of 8 cases previous chemotherapy was effective. The toxicity was primarily leucopenia (86.7%), and 9 patients received G-CSF therapy. Other toxicities (alopecia, neurologic and general fatigue) were mild. Two patients with heart failure were recognized and treated with other therapy. This chemotherapy is effective for the treatment of recurrent breast cancer.
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PMID:[Efficacy of combination chemotherapy with mitoxantrone, vincristine, doxifluridine and prednisolone for recurrence of breast cancer]. 942 66

Clinical trials of IL-3, IL-11 and thrombopoietin (TPO) against chemotherapy-induced thrombocytopenia were reviewed. Many clinical trials of IL-3 were conducted, which increased the platelet nadir counts and improved the recovery from thrombocytopenia at a dose of 5 micrograms/kg/day for 7 to 14 days. Major side effects, fever and headache, were tolerable. The combination with G-CSF was also examined. IL-11 improved the platelet nadir counts and the recovery from thrombocytopenia at a dose of 50 micrograms/kg/day for 14 days. Adverse events of IL-11 were general fatigue and edema, which were mild. Phase I/II studies of TPO were conducted, which showed a marked increase of platelet counts and improvement in recovery from thrombocytopenia. A few patients experienced mild thrombo-embolism. Improved QOL and survival benefits in the evaluation of these cytokines must be demonstrated.
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PMID:[Cytokine in cancer chemotherapy--clinical trials of IL-3, IL-11 and thrombopoietin against thrombocytopenia]. 947 25

Deferiprone, also known as L1, is an orally active iron chelator that has been studied extensively in clinical trials. The sporadic occurrence of agranulocytosis in association with deferiprone and the highly variable frequency of other possible side effects such as arthralgia have created uncertainty about the true incidence of deferiprone-related complications. A multi-center, 1-year trial was initiated to determine the safety profile of deferiprone. Using the Apotex formulation of deferiprone, 187 patients with thalassemia who were unable or unwilling to use deferoxamine were enrolled in four centers; 162 patients completed one year of therapy. Agranulocytosis (ANC < 500/mm3) occurred in one patient after 15 weeks of treatment, was not accompanied by infection and resolved following treatment with G-CSF. Nine other subjects developed less severe neutropenia (ANC 500-1500/mm3) with the lowest absolute neutrophil count reaching 500-1250/mm3. The neutropenia in these patients developed after 1-50 weeks of therapy, frequently accompanied febrile illnesses, and occurred predominantly in non-splenectomized patients. Reasons other than neutropenia for discontinuing use of deferiprone included nausea (4), voluntary withdrawal (3), high ALT (2), platelet count < 100,000/mm3 (2), low but unconfirmed ANC (1), protocol violation (1) fatigue (1), and depression (1). Mean ALT levels rose within three months of therapy and stabilized thereafter. Arthralgia and nausea and/or vomiting occurred in 6% and 24% of subjects, respectively. In this multi-center trial with weekly monitoring of blood counts, the incidence of agranulocytosis was 0.58 per 100 patient-years, and the frequency of agranulocytosis after one year was 0.5%. These findings support the safety of this formulation of deferiprone, using the careful monitoring system employed in this trial.
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PMID:A multi-center safety trial of the oral iron chelator deferiprone. 966 43

Allogeneic peripheral blood stem cell transplantation leads to an earlier engraftment compared to BMT. The feasibility, acceptance and long-term side-effects of G-CSF mobilisation of PBSC in unrelated healthy donors needs to be evaluated. Forty unrelated healthy donors received G-CSF in a dose of 10 microg/kg bodyweight for 5 days and two aphereses were performed. The donors were monitored prospectively. The data were compared to bone marrow harvests from unrelated donors. Almost all stem cell donors reported some side-effects due to Filgrastim application. Bone pain (32), headache (20), chest pain (two) and night sweats (one) were complained of. By taking analgesics, the pain was relieved in most cases. No donor discontinued the filgrastim application. Bone pain and headache resolved within 2-4 days after termination of Filgrastim application. There was, as expected, a seven-fold increase in the number of total WBCs. There were no significant changes of platelet counts during G-CSF application. After 4 weeks haemoglobin concentration and platelet counts showed no significant differences compared to baseline values. The aphereses were mostly tolerated very well. Eighteen donors reported paraesthesia, one donor developed dizziness, two complained of nausea and vomiting. There was a significant decrease in platelet count (242 before, 98 x 10(9)/l after aphereses). Autologous platelets were transfused after the second aphereses in four donors. These data were compared to data from 245 unrelated bone marrow donors, who had on average, 14 days bone pain and tiredness after donation. The G-CSF mobilisation and apheresis of peripheral blood stem cells is an alternative to traditional bone marrow harvesting in unrelated healthy donors. It is well tolerated and the duration of side-effects on average is shorter than after the surgical procedure. So far no long-term effects have been observed in the follow-up.
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PMID:Acceptance and feasibility of peripheral stem cell mobilisation compared to bone marrow collection from healthy unrelated donors. 971 88

This study was aimed to determine the activity and toxicity of combination paclitaxel and carboplatin in stage III B and IV NSCLC. Eligibililty required performance status. Paclitaxel was administered at a dose of 200 mg/m2, 3-hour infusion, followed by carboplatin at a tartgeted area under the concentration-time curve (AUC) of 6. Treatment was repeated at 3-week intervals for 6 courses. G-CSF 5 micrograms/kg was subcutaneously injected during subsequent courses if there was grade 3-4 leukopenia or granulocytopenia in the previous course. From August 1996 through June 1997, 15 patients were enrolled. The median age was 47 years (range 20-68 years), 60 per cent were female. 73.3 per cent had adenocarcinoma, and 66.7 per cent had stage III B disease. Eighty three courses were administered; 13 patients (86.7%) completed all six cycles. The objective response rate was 53.3 per cent, with 1 (6.7%) complete response and 7 (46.7%) partial responses. Pleural effusion, lung lesion and lymph node were the three most common sites that responded to chemotherapy. The major toxicity was myelosuppression. Grade 3 or 4 granulocytopenia, anemia and thrombocytopenia were observed in 18 per cent, 7.2 per cent and 1.2 per cent, respectively, of 83 courses administered. Four episodes of febrile neutropenia (4.8%) occurred in 3 patients. There was one episode of anaphylaxis during Paclitaxel infusion. Other common toxicities were mild myalgia, paresthesias, alopecia and fatigue. Most of the toxicities showed cumulative effect. Paclitaxel plus carboplatin is a moderately active regimen in advanced NSCLC. Toxicities of this regimen are well tolerated.
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PMID:Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer (NSCLC): a preliminary study. 980 67

The efficacy of the combination chemoendocrine therapy CAUT against advanced and recurrent breast cancer was examined. One course of this therapy lasted 3 weeks and consisted of adriamycin (i.v.) at 30 mg/m2 on day 1, cyclophosphamide (p.o.) at 65 mg/m2 and UFT (p.o.) at 300 mg/m2 on days 1-14, and tamoxifen (p.o.) at 20 mg/body on days 1-21. Twenty patients were enrolled, of whom 19 were eligible including seven with advanced cancer and 12 with recurrent cancer. One patient achieved CR, ten PR, three NC, and five PD, for a response rate of 58% (95% CI: 29-87%). The response rates according to type of lesion were 73% (8/11) for the soft tissue, 38% (3/8) for the bone, 20% (1/5) for the lungs and pleura, and 50% (2/4) for the liver. Adverse events with a severity of grade 3 or more included a reduction in WBC in six patients (31.6%), a reduction in RBC in one (5.3%), alopecia in four (21.1%), and severe general fatigue in one (5.3%). One patient experiencing a grade 4 reduction in WBC, and one of five patients experiencing a grade 3 reduction with a fever, recovered after treatment with G-CSF. The other four patients recovered following suspension of administration. This therapy is considered useful, exhibiting a high response rate and relatively slight adverse effects.
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PMID:[A study on the efficacy of combination chemoendocrine therapy consisting of cyclophosphamide, adriamycin, UFT, and tamoxifen for advanced or recurrent breast cancer]. 1043 80

This study was performed to determine the clinical activity and safety of paclitaxel in the treatment of patients with refractory or relapsing aggressive Non-Hodgkin's lymphoma (NHL). Between May 3, 1994 and February 16, 1996, 39 patients with refractory or relapsing NHL consented to be enrolled in two, multicenter, open-labelled studies to evaluate the efficacy, safety, time to progression and overall survival of paclitaxel given at a dose of 175 mg/m2 by a 3-hour IV infusion every three weeks without G-CSF use. Data from the two studies is combined. One patient, although registered, did not receive treatment. Of the remaining 38 patients, 17 men and 21 women aged 26-82 years (median 60) were given 104 courses of paclitaxel [median 2 (range 1-6)]. Seventeen patients had stage IV, 7 stage III, 8 stage II, 5 stage 1 and 1 unknown stage of disease. Histologic grades included 1 low, 33 intermediate, and 4 high. Three patients had bone marrow involvement. Median time from diagnosis to study entry was 19 months (1-160). The median number of previous chemotherapy regimens was 2 (range 1-6). Three of the 35 (8.6%) patients evaluable for response had partial remission (PR) of their disease for 1-7 months (median 2) and 11/35 (31.4%) stable disease (SD) for 1 to 19 months (median 3). All three responders and 3 of the 11 SD patients had received paclitaxel after relapsing from a CR. At analysis, nine of the 38 patients were alive. Median duration of follow up at analysis was 6 months (3 days-29 months). The estimated survival rates for all patients at 1 and 2 years are 34% and 27%, respectively (Kaplan-Meier) from the start of paclitaxel treatment. The median survival time was 5.4 months (3 days to 28+ months). Febrile neutropenia occurred in two patients. Seven (18%) patients developed a neutrophil nadir of < 0.5 x 10(9)/L and 2 (5%) patients developed a platelet nadir of < 50 x 10(9)/L. Six patients received blood transfusions. Non-hematologic toxicity was generally mild to moderate with all patients experiencing some toxicity. Twenty-seven patients experienced grade III toxicity including: alopecia (n = 19), pain (n = 9), fatigue (n = 5), nausea/vomiting (n = 3), diarrhoea (n = 2), pulmonary/shortness of breath (n = 2), anorexia (n = 1) and fluctuating levels of consciousness and somnolence (n = 1). Two patients experienced grade IV toxicity (infection, peripheral neuropathy, pain). No patient discontinued paclitaxel for a severe hypersensitivity reaction. In summary, administered as a 3-hour infusion, paclitaxel 175 mg/m2 results in mild myelotoxicity but minimal antitumor activity in patients with refractory NHL.
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PMID:Combined results of two phase II studies of Taxol (paclitaxel) in patients with relapsed or refractory lymphomas. 1043 66


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