Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Combined results of two phase II studies of Taxol (paclitaxel) in patients with relapsed or refractory lymphomas. 1043 66

Adverse events were analyzed in 94 normal donors who underwent PBSC harvest with G-CSF. The median dose of G-CSF was 9.7 microg/kg/day (range, 2.0-16.7), and the duration of administration was 4-6 days. Frequent symptoms were bone pain (71%), general fatigue (33%), headache (28%), insomnia (14%), anorexia (11%), nausea and/or vomiting (11%). One donor (1%) developed grade 3 toxicity bone pain (WHO criteria). WBC counts and ANC increased during G-CSF administration. After leukapheresis, three donors (3%) developed grade 3 toxicity neutropenia. Platelet counts decreased after leukapheresis. Three donors (3%) developed grade 3 thrombocytopenia. The means of both ALP and LDH increased approximately 1.9-fold compared with pretreatment levels. In one pediatric donor (1%), ALP was elevated to the grade 3 toxicity level. From multivariate analysis, the incidence of bone pain increased when G-CSF was given at a dose of 8.8 microg/kg/day or more, headaches were frequent in donors younger than 35 years, and the incidence of nausea and/or vomiting was high in female donors. The peak levels of WBC counts and ANC and post-treatment level of LDH increased in correspondence with the escalation of G-CSF dose. All adverse events normalized on follow-up evaluation. In conclusion, although PBSC harvest for normal donors is acceptable, care must be taken for all donors in terms of their sex and age as well as the G-CSF dose. We recommend less than 8.8 microg/kg/day as the G-CSF dose for PBSC mobilization in normal donors.
 ...
PMID:Peripheral blood stem cell mobilization and apheresis: analysis of adverse events in 94 normal donors. 1057 56

An important issue in allogeneic peripheral blood progenitor cell transplantation is the optimization of the regimen of mobilization of progenitor cells from normal donors. It has been shown that for G-CSF doses up to 10 microg/kg/day, a dose-response relationship exists for the degree of progenitor cell mobilization. Formal comparisons with doses higher than 10 microg/kg/day, however, have not been reported. The aim of this study was to compare the mobilization and collection results of two different G-CSF (Filgrastim) schedules: 10 microg/kg/12 h (n = 20; group A) vs 10 microg/kg/24 h (n = 20; group B). Apheresis sessions were started on day 5 (after 4 days of G-CSF). Adverse events consisted of bone pain, headache, and fatigue which required treatment with acetaminophen +/- codeine in both donor groups. Discontinuation of G-CSF administration for intolerable side-effects was not necessary in any case. The increase in peripheral leukocyte and lymphocyte counts x 109/l on day 5 was higher in group A (56.2 (37.1-75.2) and 4.4 (2. 1-14.6), respectively) than in group B (27.5 (13.2-53.9) and 2.6 (1. 9-5.1), respectively) (P < 0.0001 and P = 0.008). Platelets x 109/l decreased in group A from 228 (161-286) before G-CSF administration to 207 (155-328) on day 5 (P = 0.03), whereas no change was observed in group B. Following the first apheresis, a significant decrease in platelet count was observed with both G-CSF schedules without any differences between groups. The number x 106/kg of both nucleated and CD34+ cells collected after the first apheresis session was higher in group A (672 (462-992) and 5.9 (3.4-10.4), respectively) than in group B (427 (319-608) and 3.1 (1.1-6.8), respectively) (P = 0.0003 in both cases). The median number of CD3+cells x 106/kg collected after one apheresis session was similar with both G-CSF schedules (212 (91-430) in group A and 170 (110-291) in group B) (P = NS). In conclusion, the schedule of 10 microg/kg/12 h was well tolerated and resulted in the collection of a higher number of progenitor cells than 10 microg/kg/24 h without increasing the T cell content. This approach could avoid the donor having to undergo a second apheresis, and facilitate further graft manipulation.
 ...
PMID:Efficacy and toxicity of a high-dose G-CSF schedule for peripheral blood progenitor cell mobilization in healthy donors. 1062 34

The efficacy and safety of high-dose lenograstim on CD34 positive (CD34+) cell mobilization into peripheral blood were investigated in 18 healthy male volunteers. The volunteers were divided into 3 lenograstim dose groups of 6 subjects each. Lenograstim was administered at a dose of 2, 5, or 10 micrograms/kg/day, b.i.d. by subcutaneous injection for a total of 5 days. The median peak number of CD34+ cells/microliter of blood was 16.3, 53.9, and 96.6 in the 2, 5, and 10 micrograms/kg/day groups, respectively. A positive correlation was observed between the peak CD34+ level and dose of lenograstim (P = 0.002). The percentage of volunteers achieving more than 50 CD34+ cells/microliter of blood was significantly higher in the 10 micrograms/kg/day group (83.3%, P = 0.010) than in the 2 micrograms/kg/day group (0%). On the subject of safety, at least 1 adverse drug reaction (ADR) was observed in each of the volunteers, and a total of 12, 33, and 45 ADRs were observed in the 2, 5, and 10 micrograms/kg/day groups, respectively. A dose-dependent increase in the number of ADRs was also observed, including an elevation of LDH (P < 0.001), bone pain (P < 0.001), and fatigue (P = 0.008). However, no volunteers required symptomatic treatment or discontinuation of lenograstim. We concluded that administration of lenograstim at a dose of 10 micrograms/kg/day for 5 days is highly effective for CD34+ cell mobilization into peripheral blood and tolerable in healthy volunteers.
 ...
PMID:[Effect of lenograstim (glycosylated recombinant human granulocyte-colony stimulating factor) on peripheral blood stem cell mobilization in healthy volunteers]. 1077 48

The use of salvage chemotherapy in advanced non small cell lung cancer (NSCLC) is controversial. However, many patients need to be treated in order to achieve relief of their symptoms. Docetaxel (taxotere) is one of the most active drugs for the treatment of advanced NSCLC and several studies have also shown its effectiveness in pretreated patients. In the present study, 23 patients were treated in order to evaluate both the effectiveness and toxicity of the single agent docetaxel. Furthermore, granulocyte-colony stimulating (G-CSF) factor was administered in order to reduce neutropenia related to docetaxel. Docetaxel was administered intravenously at a dose of 100 mg/m2, on day 1, and it was repeated every 3 weeks. G-CSF was administered for primary prophylaxis of neutropenia at the standard dose of 30 mg/day from day 4 to day 10 of each cycle. The treatment was tolerated well and 5 (21.7%) partial responses were obtained. The median time to progression and the median survival time were 3 and 5 months, respectively. The main side effect noted was fatigue, the intensity of which was grade 2 in 43.4% of cases and grade 3 in 8.7% of patients, respectively. One patient (4.3%) had grade 4 cutaneous toxicity. No cases of grade 4 neutropenia were reported. In conclusion, docetaxel is active when used for salvage chemotherapy in advanced NSCLC whilst concurrent primary prophylactic administration of granulocyte-colony stimulating factor seems to decrease severe neutropenia.
 ...
PMID:Single agent docetaxel plus granulocyte-colony stimulating factor (G-CSF) in previously treated patients with advanced non small cell lung cancer. A phase II study and review of the literature. 1081 Apr

The effect of the addition of G-CSF to carboplatin, ifosfamide and doxorubicin (CIA) at the maximally tolerated dose (MTD) was studied in a phase I clinical trial. Nine patients with incurable solid tumors were treated: six endometrial and epithelial ovarian cancers, one colon cancer with pelvic masses and two unknown primary cancers. The carboplatin dose was calculated using the Calvert formula and administered in a standard 30-min intravenous infusion. The initial carboplatin dose was AUC 4.0 mg/ml per min. Fixed doses of ifosfamide (1.25 g/m2 per day), mesna (1.0 g/m2 per day, and doxorubicin (15 mg/m2 per day) were combined and given as a 4-day continuous intravenous infusion in an attempt to decrease nonhematologic toxicity. The dose-limiting toxicity of CIA was myelosuppression, mainly neutropenia and thrombocytopenia. Nonhematologic toxicities were hemorrhagic cystitis, weakness, fatigue, and nausea and vomiting. The MTD for CIA was established at the first dose level of carboplatin (4.0 mg/ml per min). Following this, G-CSF was added to the regimen in an unsuccessful effort to escalate the carboplatin dose. Free and total carboplatin pharmacokinetics were determined using flameless atomic absorption spectroscopy. There was one complete response and one partial response among eight evaluable patients. Both responding patients had advanced ovarian cancer. We conclude that carboplatin dose intensification beyond an AUC of 4.0 mg/ml per min is not made feasible by the addition of G-CSF to infusional doxorubicin and ifosfamide in patients with advanced gynecologic cancer.
 ...
PMID:A phase I trial of AUC-directed carboplatin with infusional doxorubicin and ifosfamide plus G-CSF in patients with advanced gynecologic malignancies. 1112 46

The present study was aimed at defining the antitumour activity of the cisplatin-paclitaxel-topotecan (CPT) weekly administration with G-CSF support in chemo-naive SCLC patients with extensive disease (ED-SCLC). Chemonaive ED-SCLC patients received cisplatin 40 mg/m(2), paclitaxel 85 mg/m(2), and topotecan 2.25 mg/m(2)weekly, with G-CSF (5 microg/kg days 3-5) support, for a maximum of 12 weeks. 37 patients were treated, for a total of 348 cycles delivered. 8 complete responses (22%) and 22 partial responses (59%) were recorded, giving an 81% [95% CI = 65-92%] ORR. At a 13-month (range, 4-26) median follow-up, median progression-free and overall survival were 8 months and 12.5 months, with 1-year and 2-year projected survivals of 55% and 21%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 3 patients, respectively. Only one case of neutropenic sepsis was recorded, while haemorrhagic thrombocytopenia was never observed. Diarrhoea, paraesthesias and fatigue were the main nonhaematologic toxicities being severe in 6, 2 and 10 patients, respectively. The weekly CPT combination with G-CSF support represents a well tolerated therapeutic approach in chemo-naive ED-SCLC patients. The activity rate seems at least similar to that achievable with the standard front-line approaches.
 ...
PMID:A weekly regimen of cisplatin, paclitaxel and topotecan with granulocyte-colony stimulating factor support for patients with extensive disease small cell lung cancer: a phase II study. 1133 65

Dose-dense sequential chemotherapy appears to be a promising approach in the management of patients with operable breast cancer. We evaluated the tolerability of such a novel chemotherapeutic regimen in high-risk patients. From February 1995 until September 1997, 49 women with histologically confirmed breast cancer and > or =10 involved axillary nodes were treated postoperatively with three cycles of epirubicin (110 mg/m(2)) followed by three cycles of paclitaxel (250 mg/m(2) in a 3-hour infusion) followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m(2), methotrexate 57 mg/m(2), fluorouracil 840 mg/m(2); E-T-CMF). All cycles were repeated every 2 weeks with G-CSF support. Ovarian ablation with monthly injections of triptorelin for 1 year was performed in premenopausal patients and tamoxifen was prescribed for 5 years to all women with positive receptor status after the completion of chemotherapy. A total of 456 cycles of chemotherapy were administered, 363 (80%) of them at full dose. Forty-seven (96%) patients received all 9 cycles of chemotherapy. Relative dose intensity of epirubicin was 0.98, of paclitaxel 0.97, of cyclophosphamide 0.99, of methotrexate 0.98 and of fluorouracil 0.99. Grade 3--4 toxicities included anemia (8%), leukopenia (8%), peripheral neuropathy (6%), neutropenia (4%), thrombocytopenia (4%), stomatitis (2%), diarrhea (2%), fatigue (2%) and hypersensitivity reaction (2%). Febrile neutropenia occurred in 2 patients. Alopecia was universal. After a median follow-up of 3 years, 11 women (22%) relapsed and 4 (8%) died. The 3-year actuarial disease-free survival rate was 72% and the 3-year overall survival rate 90%. The E-T-CMF regimen is well tolerated, as adjuvant treatment, in patients with operable breast cancer with promising activity and deserves further evaluation in phase III studies.
 ...
PMID:Dose-dense sequential adjuvant chemotherapy with epirubicin, paclitaxel and CMF in high-risk breast cancer. 1134 Mar 72

Histamine is a classical, but still interesting inflammatory mediator. Many people have long believed that histamine is derived from mast cells or basophils alone. However, the histamine-forming enzyme, histidine decarboxylase (HDC), is induced in a variety of tissues in response (i) to gram-positive and gram-negative bacterial components (lipopolysaccharides, peptidoglycan, and enterotoxin A) and (ii) to various cytokines (IL-1, IL-3, IL-12, IL-18, TNF, G-CSF, and GM-CSF). HDC is induced even in mast-cell-deficient mice. The histamine newly formed via the induction of HDC is released immediately and may be involved in a variety of immune responses. Reviewing our work and that of Schayer and Kahlson, the pioneers in this field, lead us to the conclusion that nowadays we need to understand that histamine can be produced via the induction of HDC by a mechanism coupled with the cytokine network. We call this histamine "neohistamine", to distinguish it from the classical histamine derived from mast cells or basophils. Neohistamine is involved in physiological reactions, inflammation, immune responses and a variety of diseases such as periodontitis, muscle fatigue (or temporomandibular disorders), stress- or drug-induced gastric ulcers, rheumatoid arthritis, complications in diabetes, hepatitis, allograft rejection, allergic reactions, tumor growth, and inflammatory side effects of aminobisphosphonates.
 ...
PMID:[Induction of histidine decarboxylase in inflammation and immune responses]. 1149 27

Thirty-nine patients with advanced non-small cell lung cancer, refractory or resistant to platinum or taxanes derivatives were treated on an out-patient basis with vinorelbine 25 mg/m2 intravenous (I.V.) on days 1 and 8 followed by gemcitabine 800 mg/m2 l.V. on days 1 and 8. Chemotherapy was repeated every 3 weeks. The patients were evaluated for response every two cycles of treatment. All 39 patients were assessable for toxicity and 35 were assessable for response. On an intent to treat analysis, only 1 (2.6%) patient achieved a partial response (PR) (95% CI 0.09% to 17.6%); fourteen patients (35.9%, 95% CI 29.45% to 67.4%) had stable disease (SD) and 24 (61.5%) had progressive disease (PD). The median time to tumor progression (TTP) was 4.7 months (range 0.13 to 18.9 months), the median survival time was 7.3 months (range 0.6 to 18.9 months) and the 1-year survival rate was 35%. Clinical benefit response including improvement of PS, dyspnea and anorexia, pain and cough reduction and cessation of hemoptysis and fever was observed in 10% to 50% of patients. Grade 3/4 neutropenia occurred only in 2 (5.2%) patients. Five patients experienced febrile neutropenia, which was successfully treated with G-CSF and broad-spectrum antibiotics. No patient experienced grade 3/4 anaemia or thrombocytopenia. One patient experienced grade 4 fatigue and stopped the treatment. Nausea / vomiting, fatigue, neurotoxicity, diarrhea and fever were mild in the majority of patients and did not result in any clinically significant problem. There were no treatment-related deaths. In conclusion, the combination of gemcitabine and vinorelbine showed low objective response rate in patients previously treated with CDDP/taxanes-containing regimens. This regimen was relatively well-tolerated and was associated with prolonged 1-year survival and improvement in cancer related symptoms. To validate these findings a randomized trial of gemcitabine and vinorelbine versus taxotere or best supportive care is required.
 ...
PMID:An out-patient second-line chemotherapy with gemcitabine and vinorelbine in patients with non-small cell lung cancer previously treated with cisplatin-based chemotherapy. A phase II study of the Hellenic co-operative Oncology Group. 1171 2


<< Previous 1 2 3 4 5 Next >>