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)

From October 1995 to June 1997, 19 chemotherapy-naive patients with pathology-proven locally advanced or metastatic biliary tract carcinomas (BTC) were enrolled. The regimen consisted of 5-fluorouracil (5-FU) 2600 mg/m2 and leucovorin (LV) 150 mg by weekly 24 h infusion for 6 weeks and followed by a 2 week break. The treatment was terminated if disease progressed, the patient refused or unacceptable toxicity occurred. All patients required a Port-A catheter insertion and were treated at outpatient clinics by portable infusion pumps. There were 12 males and seven females with a median age of 62 years (range 45-77). The primary tumor sites were nine intrahepatic cholangiocarcinomas (CC), three perihilar CC, one distal BTC and six gallbladder cancers. A total of 179 chemotherapy sessions were given with a mean of 9.5 (range 2-18). Eighteen patients were evaluable for response. The response rates were: 33% (six of 18) partial response (PR), 39% (seven of 18) stable disease (SD) and 28% (five of 18) progressive disease (PD). All of the patients were evaluable for toxicity. The most common toxicities were mild fatigue (nine of 19, 47%), loss of appetite (nine of 19, 47%), skin hyperpigmentation (five of 19, 26%) and diarrhea (two of 19, 11%). Only one patient had grade IV myelotoxicity with sepsis but without treatment-related death. The median time to progression was 4 months. The overall median survival time was 7.0 months. The median survival time of the PR was not reached, SD was 8.0 months and PD 3.5 months. In conclusion, weekly high-dose 5-FU with LV by 24 h infusion in an outpatient setting for patients with BTC is effective, only mildly toxic and deserves further study.
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PMID:Weekly 24 h infusion of high-dose 5-fluorouracil and leucovorin in patients with biliary tract carcinomas. 966 May 35

The Lambert-Eaton syndrome is an autoimmune disease affecting the presynapse of the neuromuscular junction. Proximal muscle fatigue of the limbs is improved by repeated maximal voluntary contractions. Generally, patients present hypo or areflexia and frequently a dry mouth syndrome. In 50% of the cases, the Lambert-Eaton syndrome is associated with small-cell bronchogenic carcinoma. The different treatments proposed in the literature for Lambert-Eaton paraneoplastic syndrome focus on treatment of the primary tumor. Symptomatic treatment of the junctional disorder are based on cholinergic drugs, immunosuppression and immunomodulation, useful in case of unsuccessful antineoplastic therapy.
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PMID:[Treatment of the paraneoplastic Lambert-Eaton syndrome]. 976 89

A late phase II clinical study of RP56976 (docetaxel) was conducted in patients with advanced/recurrent gastric cancer as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of the 76 patients enrolled, 66 patients were eligible and 59 patients were evaluable for response. One patient showed complete response (CR), 13 patients partial response (PR), 1 patient minor response (MR), 19 patients no change (NC) and 25 patients had progressive disease (PD). The overall response rate in 59 evaluable patients was 23.7% (95% CI = 13.6-36.6%). The primary tumor showed a 4.3% (1/23) response, while the metastatic lesions in the abdomen, pelvic mass, lung, liver, and lymph nodes showed response rates of 62.5% (5/8), 33.3% (1/3), 33.3% (1/3), 14.8% (4/27), and 13.9% (5/26), respectively. About hematological toxicity, severe (Grade 3 or more) leukopenia was observed in 36 patients (56.3%) and neutropenia in 52 patients (81.3%). Other major toxicity (Grade 3 or more) included nausea/vomiting in 11 patients (17.2%), anorexia in 9 patients (14.1%), fatigue in 5 patients (7.8%), and alopecia in 7 patients (10.9%), all which were tolerable. The results show that docetaxel is an effective anticancer agent for advanced/recurrent gastric cancer.
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PMID:[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent gastric cancer: a Japanese Cooperative Study Group trial (group A)]. 979 14

A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer was performed to evaluate the anti-tumor activity and clinical toxicity as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of 72 patients enrolled, 63 patients were eligible and 59 patients were evaluable for response. The anti-tumor effects obtained complete response (CR) in one patient partial response (PR) in 13, minor response (MR) in 3, no change (NC) in 20, and progressing disease (PD) in 22 patients. The overall response rate in 59 patients was 23.7% (14/59). For 14 CR or PR cases, a response appeared 10 to 107 days (median 33.5 days) and 1 to 8 (median 2) times of dosing after the initial administration. The response rate was 9.5% in the primary tumor, 31.3% livers, 50.0% abdominal tumor, and 24.1% lymph nodes, respectively. The major adverse reactions were gastrointestinal symptoms including nausea/vomiting, anorexia, fatigue, alopecia and fever. Leukocytopenia and neutrocytopenia were also observed with a high incidence, but they recovered after 8 days from the nadir. The results show that docetaxel is an effective anti-tumor agent for advanced or recurrent gastric cancer. It is necessary to conduct another clinical trial by concomitant administration with other anti-tumor agents.
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PMID:[A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer: a cooperative study group trial (group B)]. 1009 45

We reported previously that the addition of recombinant Escherichia coli human granulocyte-macrophage colony stimulating factor (GM-CSF) to a 5-fluorouracil (5-FU) and leucovorin (LV) regimen seemed to ameliorate diarrhea and permit increased 5-FU dose intensity (J. L. Grem et al., J. Clin. Oncol., 12: 560-568, 1994). We then tested the effect of GM-CSF given with a more toxic regimen of 5-FU/LV/IFN-alpha (IFN alpha-2a). Thirty-one patients with a good performance status and no prior chemotherapy for systemic disease received IFN alpha(-2a (5 MU/m2 s.c., days 1-7), 5-FU (370 mg/m2 i.v., days 2-6), LV (500 mg/m2 i.v., days 2-6), and GM-CSF (Saccharomyces cerevisiae 250 microg/m2 s.c., days 7-18) every 3 weeks. Toxicities and 5-FU dose intensity were compared with that observed in our prior Phase II trial with 5-FU/LV/IFN alpha-2a (J. L. Grem et al., J. Clin. Oncol., 11: 1737-1745, 1993). In comparison with the prior Phase II study, the WBC and granulocyte nadirs in the present trial were significantly higher. When trends in toxicity grades for all cycles were compared, stratifying for 5-FU dose, the incidence and severity of mucositis, skin rash, WBC toxicity, and granulocyte toxicity were significantly lower in the present trial, whereas nausea/vomiting and fatigue were significantly worse. The delivered 5-FU dose intensity for all cycles of therapy appeared to be significantly higher in the present trial. Six of 28 evaluable patients had a partial response (21.4%), and 13 (46%) had stable disease for > or =12 weeks. Despite treatment-related toxicity, patient quality of life did not worsen during the study. No correlation was observed between thymidylate synthase content in primary tumor specimens and response, time to treatment failure, or survival. The addition of GM-CSF appeared to decrease the severity of leukopenia, granulocytopenia, mucositis, and skin rash when compared with our prior experience with this regimen of 5-FU/LV/IFN alpha-2a, at the cost of greater nausea/vomiting and fatigue. The potential impact of increased 5-FU dose intensity on clinical response, however, remains to be determined.
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PMID:A pilot study of interferon alpha-2a, fluorouracil, and leucovorin given with granulocyte-macrophage colony stimulating factor in advanced gastrointestinal adenocarcinoma. 1049 10

Hemangiomas represent the most common primary tumor of the liver. Clinically the significance of these lesions is highly variable. The management of hemangiomas is controversial and is intimately related to the size, symptoms, and associated comorbidities of the patients who harbor these benign tumors. Series suggest that the vast majority of hemangiomas are less than 4 cm, asymptomatic, and clinically incidental findings. Symptomatic hemangiomas are large and associated with a constellation of vague upper abdominal complaints including pain, mass, distention, early satiety, and weight loss. A number of small series of surgically treated symptomatic hemangiomas have demonstrated enucleation as a safe and effective intervention. We report a collection of case reports using embolization as a primary treatment of symptomatic hemangiomas. The first patient is a 73-year-old black man previously treated for prostate cancer by radical prostatectomy and radiation. He developed weight loss, abdominal fullness, and early satiety. His symptoms were attributed to a large left lateral segmental liver mass that was biopsy proven to be a hemangioma. The second patient is a 49-year-old black women who complained of weakness, fatigue, night sweats, and anemia. The only abnormality discovered was a large right posterior hemangioma. The third patient is a 49-year-old black women with unexplained right upper quadrant pain and anemia who was found to have a 19 x 11 x 7.5-cm left hepatic hemangioma by CT. All three patients underwent elective treatment of their hemangiomas with highly selective hepatic embolization. There were no significant complications related to the procedures. Symptoms resolved for all patients acutely after treatment. The use of embolization for hepatic hemangiomas provides safe and effective treatment of the patient's symptoms while avoiding operative intervention, extended hospitalization, or postoperative recuperation. This treatment modality should be considered for the symptomatic hemangioma under elective conditions.
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PMID:Embolization for management of hepatic hemangiomas. 1124 41

Quality of life (QoL) is estimated from patients scores to items related to everyday life, including rest and activity. The rest-activity rhythm reflects endogenous circadian clock function. The relation between the individual rhythm in activity and QoL was investigated in 200 patients with metastatic colorectal cancer. Patients wore a wrist actigraph (Ambulatory Monitoring Inc., New York. NY) for 3-5 d before chronotherapy, and completed a QoL questionnaire developed by the European Organization for Research and Treatment of Cancer (QLQ-C30) plus the Hospital Anxiety and Depression Scale. The rest-activity circadian rhythm was characterized by the mean activity level (m), autocorrelation coefficient at 24h (r24), and the dichotomy index (I < O). a ratio between the amount of activity while in and out of bed. The distribution of the rest-activity cycle parameters and that of QoL scores was independent of sex, age, primary tumor, number of metastatic sites, and prior treatment. Both the 24h rhythm indicators were positively correlated with global QoL score as well as physical, emotional, and social functioning. Negative correlations were found between m, r24, or I < O and fatigue, appetite loss, and nausea. The rest-activity circadian rhythm appeared to be an objective indicator of physical welfare and QoL. This analysis suggests that circadian function may be one of the biological determinants of QoL in cancer patients.
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PMID:Contribution of the rest-activity circadian rhythm to quality of life in cancer patients. 1196 84

A 62-year-old female patient was hospitalized for general fatigue and appetite loss. Type 3 gastric cancer (moderate differentiated adenocarcinoma) with liver metastasis (S8) and direct invasion to the retro-peritoneal space and duodenal third portion was detected by endoscopic and radiographic examination. This case was judged to be unresectable from these findings. TS-1 plus divided administration of CDDP was performed. TS-1 (100 mg/day) was administrated from day 1 to 21 followed by 14 days rest as one course. CDDP (20 mg/m2) was infused for 2 hours on day 1, 8, and 15. One course was done in the hospital, and the following 2 courses as ambulatory treatment. Grade 2 neutropenia was observed as an adverse reaction. At the completion of 3 courses, partial response in the primary tumor, complete response in the duodenal third portion and no change in the liver metastasis were assessed by examination. Because of this remarkable down-staging, distal gastrectomy and radiofrequency ablation (RFA) for liver metastasis were performed. There was no evidence of direct invasion to the other organs from the primary tumor in intraoperative findings. Pathological examination revealed the disappearance of carcinoma cell in the resected stomach and the surrounding lymphnodes. In conclusion, this chemotherapy regimen has an excellent antitumor effect with low toxicities. Therefore, this regimen was comparatively safe for outpatients and was an effective neo-adjuvant chemotherapy.
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PMID:[Complete response of primary tumor in a case of advanced gastric cancer with liver metastasis treated by TS-1 plus divided administration of CDDP]. 1458 84

Within the past decade, clinical trials have shown that the presence of anemia can diminish the physical status, functional abilities, and overall quality of life (QOL) of cancer patients and can negatively influence the outcome of their treatment. However, recent preclinical and clinical studies have also shown that increasing hemoglobin levels by administering recombinant human erythropoietin (rHuEPO, epoetin alfa) may ameliorate anemia and, in doing so, improve QOL and possibly result in better treatment outcomes following radiotherapy, chemotherapy, or a combination of these modalities. Several mechanisms by which rHuEPO may improve treatment outcome have been proposed, including correction of tumor hypoxia, increased sensitivity of tumor cells to radiotherapy and chemotherapy, correction of anemia and its associated symptoms (particularly fatigue), and immune-modulated effects of rHuEPO on tumor growth. Improvement of tumor oxygenation by rHuEPO could affect treatment outcome in two ways. First, correction of hypoxia results in the downregulation of hypoxia-inducible factor 1 (HIF-1), a key regulator of cellular adaptive responses to hypoxia (e.g., angiogenesis), including many pathways that are important for tumor growth and metastasis. Interruption of the HIF-1 pathway not only limits growth of the primary tumor but also reduces the potential for the development of more aggressive tumors and metastatic spread, which could ultimately improve treatment outcome. Second, within the tumor, it is the hypoxic cells that are resistant to oxygen-dependent radiotherapy and chemotherapy, and improvement in their oxygenation would increase their sensitivity to the cytotoxic effects of such treatment. Correction of anemia and its associated symptoms, particularly fatigue, can have a beneficial effect on patient QOL, and this in turn may translate into greater tolerance of radiotherapy and chemotherapy, allowing patients to receive full doses and on-schedule dosing, and thus have an increased likelihood of a therapeutic response. Lastly, results of a study using a murine model of multiple myeloma have indicated that rHuEPO may induce an immune-mediated antitumor effect. Therefore, additional research is warranted to further explore the biologic actions of rHuEPO and to determine their relevance to therapeutic outcome.
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PMID:rHuEPO and improved treatment outcomes: potential modes of action. 1559 21

Twenty-two patients with metastatic renal cell carcinoma and removal of the primary tumor were treated with subcutaneous pegylated interferon alfa-2b (PEG-Intron) to evaluate toxicity and efficacy. Start dose was 3.0 microg/kg/week, escalated to 6.0 microg/kg/week. After 2 months, therapy was extended in case of response or stable disease (SD) until progressive disease (PD) or relapse for a maximum of 2 years. National Cancer Institute common toxicity criteria (NCI-CTC) were monitored every 2-4 weeks. After 2 months, nine patients did not continue (8 PD, 1 SD with grade 4 CTC) and 13 extended treatment [three partial response (PR), 10 SD], of these, 11 progressed. One patient with PR developed a durable complete response later. Overall response rate was 13.6% (3/22). Median overall survival is 13 months (range 3-35 months). Dosage was escalated to 6 microg/kg/week in three patients. NCI-CTC grade 2 and 3 required dose attenuation in 12 patients during escalation, and reduction in 10 during the trial. Three patients discontinued because of grade 4 CTC (two fatigue, one hyperglycemia). Fatigue was the major dose-limiting toxicity. These results suggest an efficacy and toxicity of PEG-Intron comparable to standard interferon alfa-2b in patients with mRCC and removal of the primary tumor.
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PMID:A phase-II study of pegylated interferon alfa-2b for patients with metastatic renal cell carcinoma and removal of the primary tumor. 1562 13


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