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)

Both paclitaxel and gemcitabine (Gemzar) have shown activity and manageable toxicity when used as single agents in heavily pretreated patients with metastatic breast cancer. This phase II study evaluated their use in combination for metastatic breast cancer patients whose disease recurred or progressed following treatment with anthracycline-containing regimens. Twenty-nine patients ranging from 32 to 68 years of age received paclitaxel at 175 mg/m2 i.v. over 3 hours on day 1 and gemcitabine at 1,000 mg/m2 i.v. on days 1, 8, and 15 every 28 days. Because of unacceptable thrombocytopenia in the first five patients, the gemcitabine schedule was changed to days 1 and 8 of a 21-day cycle for the remainder of the study. All 29 patients were evaluable for response and toxicity. Seventeen patients (59%) were considered truly anthracycline- or anthracenedione-refractory. A total of 137 cycles (median: 4 per patient) were administered. The regimen was well tolerated. Grade 3/4 thrombocytopenia was observed in 5 (18.5%) of the first 27 cycles and in 6 (5.4%) of the 110 cycles following dosage reduction (P = .04). Five patients had grade 1 and two patients had grade 3 neuropathy. Eight patients had grade 3 neutropenia, two had grade 4 neutropenia with fever at the higher dosage, and eight had grade 1/2 myalgia and fatigue. Five patients (17%) had a complete response and 11 (38%) a partial response, yielding an objective response rate of 55% (95% confidence interval = 36%-73%). Six patients (20.7%) had stable disease. Median response duration was 8 months (range: 4-26 months), and median overall survival was 12 months (range: 4-48+ months). Survival at 1, 2, 3, and 4 years was 45%, 30%, 20%, and 10%, respectively. The combination of paclitaxel on day 1 with gemcitabine on days 1 and 8 of a 21-day cycle appears to have promising activity in heavily pretreated patients with metastatic breast cancer. Phase III trials comparing this promising doublet to paclitaxel monotherapy and to other chemotherapeutic strategies for advanced breast cancer will clarify the role of this regimen.
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PMID:Paclitaxel and gemcitabine as salvage treatment in metastatic breast cancer. 1476 2

Aromatase inhibitors and inactivators are playing an increasing greater role in breast cancer treatment. Exemestane, a highly specific, steroidal aromatase inactivator, is the newest agent in this class. The drug is highly specific, and inhibits the in vivo conversion of androstenedione to oestrone (aromatization) by a mean of 97.9%. Exemestane has shown good efficacy and tolerability in multiple clinical trials among patients with metastatic breast cancer who have failed one or more previous hormonal therapies. Exemestane 25 mg/day slows disease progression and reduces tumour-related signs and symptoms and the drug exhibits a partial lack of cross-resistance with the non-steroidal aromatase inhibitors. Response rates to exemestane of 14% to 29% were observed including patients with visceral metastases, who have historically proven difficult to treat. In a large phase III trial, exemestane was found to be superior to megestrol acetate with respect to time to progression and overall survival. In addition, exemestane is currently under investigation as first-line therapy in metastatic disease and in sequence with tamoxifen in the adjuvant setting. Adverse events include low-grade hot flashes, nausea, and fatigue--mostly of mild to moderate intensity--and treatment-related discontinuations are rare. In conclusion, exemestane represents a novel and interesting drug for the treatment of advanced breast cancer, with exciting prospects for use in adjuvant therapy and, potentially, breast cancer prevention.
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PMID:Exemestane: a review of its clinical efficacy and safety. 1496 85

The potential value of baseline health-related quality-of-life (HRQOL) and clinical factors in predicting prognosis was examined using data from an international randomised phase III trial which compared doxorubicin and paclitaxel with doxorubicin and cylophosphamide as first line chemotherapy in 275 women with metastatic breast cancer. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the related breast module (QLQ-BR23) were used to assess baseline HRQOL data. The Cox proportional-hazards regression model was used for both univariate and multivariate analyses of survival. In the univariate analyses, performance status (P<0.001) and number of sites involved (P=0.001) were the most important clinical prognostic factors. The HRQOL variables at baseline most strongly associated with longer survival were better appetite, physical and role functioning, as well as less fatigue (P<0.001). The final multivariate model retained performance status (P<0.001) and appetite loss (P=0.005) as the variables best predicting survival. Substantial loss of appetite was the only independent HRQOL factor predicting poor survival and was strongly correlated (/r/>0.5) with fatigue, role and physical functioning. In addition to known clinical factors, appetite loss appears to be a significant prognostic factor for survival in women with metastatic breast cancer. However, the mechanism underlying this association remains to be precisely defined in future studies.
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PMID:Baseline health-related quality-of-life data as prognostic factors in a phase III multicentre study of women with metastatic breast cancer. 1509 77

Breast cancer in elderly patients (70+) is a major health problem that will only increase in the future. Besides adequate local treatment and hormone therapy, there can be an indication for chemotherapy in this patient group. Due to concerns of excessive toxicity, there is often a defeatist attitude towards chemotherapy in elderly patients. As taxanes are considered to be the most effective drugs in breast cancer, and as the weekly regimens seem at least as effective as the 3-weekly regimens but with less toxicity, these weekly regimens are very attractive for elderly breast cancer patients. Many different doses have been used for the weekly taxane regimens in phase II trials. Although large comparative studies are lacking, pharmacological studies are suggestive for a decreased clearance of both paclitaxel and docetaxel in elderly patients compared to non-elderly patients. It seems therefore safe to use the lower range of proposed doses of the weekly regimens until further data provide stronger evidence for optimal dosing in elderly patients. A dose of paclitaxel 80 mg/m(2)/week and docetaxel 36 mg/m(2)/week seems tolerable for elderly patients without excessive toxicity and with impressive response rates. The dose limiting toxicity for 3-weekly taxanes, severe neutropaenia, is generally very limited in weekly regimens, also in the elderly or frail patients. However, neuropathy (paclitaxel) or fatigue and fluid retention (docetaxel) can be troublesome, and eventually require dose modifications. In general however, weekly taxanes are a reasonable option for older patients with metastatic breast cancer.
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PMID:Taxanes in elderly breast cancer patients. 1514 8

Recombinant human erythropoietin (r-HuEPO) corrects cancer-related anemia and, thereby, improves quality of life. The purpose of the present study was to measure the impact of erythropoietin on hemoglobin and mood state in patients with metastatic breast cancer and mild anemia (Hgb < 12.0 g/dL). Women were randomized to receive usual care (G1) or usual care plus r-HuEPO (G2). Usual care included transfusions as necessary and fatigue education. R-HuEPO was begun at 40,000U subcutaneously per week. At 4 weeks, the dose was increased to 60,000U if Hgb had not increased > or = 1.0 g/dL. The drug was discontinued at 8 weeks if hemoglobin improvement was < 1.0 g/dL. The study was terminated early (n = 27, G1 = 13, G2 = 14) when 4/14 (28.5%) subjects in G2 developed thrombotic events (deep vein thrombosis [DVT] in 1; DVT plus pulmonary embolism [PE] in 1; DVT plus PE 1 month after drug discontinuation in 1; and brachial vein thrombosis with infected Mediport in 1). In all four patients, Hgb levels were normal at the time of the event. No patient in G1 developed a thrombotic event. There were no significant differences in demographic characteristics or current chemotherapy regimen in G1 vs. G2. The decision to terminate the trial was made after considerable deliberation. The increased incidence of thrombotic events in the r-HuEPO (G2) arm of this study exceeds that in prior studies in this population and prior r-HuEPO trials. This may relate to the administration of r-HuEPO in this high-risk population, but the small sample size and possible predisposing risk factors preclude definitive conclusions.
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PMID:The decision to prematurely terminate a trial of R-HuEPO due to thrombotic events. 1515 43

The purpose of this exploratory, secondary analysis was to compare the prevalence of symptoms attributable to breast cancer or its treatment and to identify and describe symptom clusters across 3 phases of the disease. A pooled analysis was conducted by combining existing symptom data collected at the baseline assessment from 3 independent studies of women with breast cancer. Study I had 40 women with early-stage breast cancer following primary surgery for their disease and prior to the initiation of adjuvant therapy. Study II had 88 women with stage I, II, or III breast cancer who had completed surgery and adjuvant chemotherapy and may have been receiving hormonal therapy. Study III had 26 women with metastatic breast cancer (stage IV). Three symptom clusters were identified corresponding to 3 different phases of the breast cancer experience. Each cluster was composed of symptoms related to fatigue, perceived cognitive impairment, and mood problems. Future studies are needed to prospectively examine whether these symptoms cluster across 3 phases of breast cancer and the effect of these clusters on the functional ability and quality of life in women with breast cancer.
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PMID:Symptom clusters in breast cancer across 3 phases of the disease. 1591 67

Standard dose docetaxel is burdened by severe toxicity. Weekly schedules have been shown to be active as standard scheme with reduced side effects. In 20-30% of elderly patients (pts) the classic 6-week schedule induces grade 3/4 fatigue and other cumulative toxicities. We carried out this safety study in order to evaluate whether a modified weekly docetaxel schedule would improve the toxicity profile. Twenty-one untreated elderly (> or = 70 years) pts suffering from metastatic breast cancer were enrolled in the study. Pts were treated with a weekly dose of 35 mg/m2 docetaxel for 6 weeks, followed by a 2-week rest. Further cycles were performed with this modified schedule: docetaxel days 1, 8 and 15 every 29 days. All pts received at least the first cycle (6 weeks). A total of 261 doses were delivered. No toxic deaths occurred. The toxicity was mild: we recorded 1 episode of grade 3 neutropenia and severe asthenia in only 2 pts (10%). We recorded an overall response rate of 33% (1 CR, 6 PR). Our data showed a reduced incidence of severe asthenia (2/21), obtained with a light modification of a weekly docetaxel schedule.
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PMID:A modified weekly docetaxel schedule as first-line chemotherapy in elderly metastatic breast cancer: a safety study. 1592 Sep 13

Granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]) is a powerful cytokine that is able to stimulate the generation of dendritic cells. Adjuvant treatment with continuous low-dose GM-CSF has been shown to prolong survival of stage III/IV melanoma patients. Data on continuous low-dose GM-CSF therapy in tumors other than prostate cancer are still lacking. This pilot trial was initiated in order to evaluate the efficacy and tolerability of continuous low-dose GM-CSF as salvage in various chemotherapy-refractory carcinomas. A total of 19 patients who had failed a median of 4 prior chemotherapies were included. Their malignancies included metastatic breast cancer, recurrent ovarian carcinoma, metastatic endometrial carcinoma, and recurrent squamous cell cancer of the cervix uteri. Continuous low-dose GM-CSF was delivered subcutaneously at a daily starting dose of 125 microg. GM-CSF was increased at 25-microg increments until a maximum of 250 microg was reached or when mild leukocytosis (10-20 g/L) was achieved, providing that the relative eosinophil count did not exceed 15%. Therapy was continued until progression or refusal by the patient. Toxicity was generally mild. Only one patient was withdrawn due to grade 3 fatigue. In three additional patients, temporary dose reduction was necessary because of grade 1 injection site reactions, which recovered spontaneously. Mild to moderate leukocytosis was obvious in 10 patients. Systemic hypersensitivity-like reactions did not occur and no patient required hospitalization for other life-threatening side effects. The objective response rate was 37%: 1 complete and 6 partial responses, 4 disease stabilizations, 8 progression of disease. Median response duration was 6 months. Notably, 6 of 7 responders but only 1 of 8 patients with disease progression developed leukocytosis during therapy. Therefore, we conclude that continuous low-dose GM-CSF has substantial activity in heavily pretreated patients with either metastatic breast cancer or female genital tract cancer. Achievement of mild leukocytosis seems to be a predictor of response.
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PMID:Continuous low-dose GM-CSF as salvage therapy in refractory recurrent breast or female genital tract carcinoma. 1593 97

We evaluated the efficacy and toxicity profile of single-agent docetaxel administered in daily clinical practice at low-dose regimen in 37 pre-treated elderly patients with metastatic breast cancer previously exposed to chemotherapy. Docetaxel was employed by physician's preference according to a weekly (8 patients, 25-30 mg/m2 every 7 days), bi-weekly (19 patients, 40-50 mg/m2 every 14 days), or tri-weekly (10 patients, 75-100 mg/m2 every 21-28 days) schedule. The median age of patients was 70 yrs, and most of them (84%) had a good PS; visceral metastases were found in 26 patients. Twenty-five patients were pre-treated by two or more chemotherapy lines. Anthracycline or anthracycline/paclitaxel therapy was previously employed in 25 patients (67%). Median delivered dose-intensity of docetaxel was 21 mg/m2/week (range 11-32), without significant differences between the regimens used. Thirty-three patients were evaluable for response. Eight (24%) patients had objective responses (2 complete and 6 partial) to docetaxel, with a median duration of response of 18 months; 14 (42%) patients had stable disease lasting more than 6 months (median 10 months). Median overall time to progression was 6 months. Median overall survival was 16 months, with 1- and 2-year survival rates of 64% and 34%, respectively. Grade 3/4 toxicities were rare: leucopenia in 18% of patients, neutropenia in 13%, emesis in 8%, diarrhea in 5%, and mucositis in 5%. Severe fatigue was recorded in 4 patients. In conclusion, docetaxel, even when administered at low dose-intensity, demonstrated good disease control and toxicity profile. This approach provides an excellent alternative for pre-treated elderly patients with advanced breast cancer.
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PMID:Low dose-intensity docetaxel in the treatment of pre-treated elderly patients with metastatic breast cancer. 1594 30

The aim of the study was to obtain United Kingdom-based societal preferences for distinct stages of metastatic breast cancer (MBC) and six common toxicities. Health states were developed based on literature review, iterative cycles of interviews and a focus group with clinical experts. They described the burden of progressive, responding and stable disease on treatment; and also febrile neutropenia, stomatitis; diarrhoea/vomiting; fatigue; hand-foot syndrome (grade 3/4 toxicities) and hair loss. One hundred members of the general public rated them using standard gamble to determine health state utility. Data were analysed with a mixed model analysis. The study sample was a good match to the general public of England and Wales by demographics and current quality of life. Stable disease on treatment had a utility value of 0.72, with a corresponding gain of +0.07 following a treatment response and a decline by 0.27 for disease progression. Toxicities lead to declines in utility between 0.10 (diarrhoea/vomiting) and 0.15 (febrile neutropenia). This study underlines the value that society place on the avoidance of disease progression and severe side effects in MBC. This may be the largest preference study in breast cancer designed to survey a representative general public sample.
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PMID:Health state utilities for metastatic breast cancer. 1696 55


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