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 late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.
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PMID:[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer]. 998 6

5-Fluorouracil (5-FU) is an effective enhancer of radiation therapy (RT) in head and neck cancers. Due to rapid, predominantly hepatic metabolism by dihydropyrimidine dehydrogenase (DPD) and suggested clinical benefit from prolonged drug exposure, 5-FU is commonly given by continuous infusion. Eniluracil is a novel DPD-inactivator designed to prolong the half-life of 5-FU and provide sustained plasma concentrations of 5-FU with oral dosing. We conducted a Phase I study of the safety and efficacy of eniluracil given with oral 5-FU in patients receiving concurrent RT for recurrent or advanced squamous cell carcinomas of the head and neck. Thirteen patients with recurrent, metastatic, or high-risk (defined as an expected 2-year survival rate of <10%) head and neck cancer were enrolled and treated with concomitant chemoradiotherapy on an every-other-week schedule. Eniluracil at a fixed dose [20 mg twice a day (BID)] was given for 7 consecutive days (days 1-7). 5-FU and RT were given on 5 consecutive days (days 2-6). One patient was treated with once-daily RT (2.0 Gy fractions). The remaining patients received hyperfractionated RT (1.5-Gy fractions BID). The initial dose of 5-FU was 2.5 mg/m2 given BID. Dose escalation in patient cohorts was scheduled at 2.5-mg/m2 increments, with intrapatient dose escalation permitted. Lymphocyte DPD activity and serum 5-FU and uracil concentrations were monitored during two cycles. DPD activity was completely or nearly completely inactivated in all patients. Sustained, presumed therapeutic concentrations of 5-FU were observed at a dose of 5.0 mg/m2 given BID. Cumulative dose-limiting myelosuppression (both neutropenia and thrombocytopenia) was observed during the fourth and fifth cycles following administration of 5.0 mg/m2 5-FU BID. One patient died of neutropenic sepsis during cycle 4. Other late cycle toxicities included diarrhea, fatigue, and mucositis. Grade 3 mucositis was observed in 4 patients, but no grade 4 mucositis or grade 3 or 4 dermatitis was observed. A second patient death occurred during cycle 1 of treatment. No specific cause of death was identified. The study was subsequently discontinued. Cumulative myelosupression was the significant dose-limiting toxicity of oral 5-FU given with the DPD-inactivator eniluracil on an every-other-week schedule. Clinical radiation sensitization was not observed, based on the absence of dose-limiting mucositis and dermatitis. Alternative dosing schedules need to be examined to determine the most appropriate use of eniluracil and 5-FU as radiation enhancers.
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PMID:Phase I study of eniluracil, a dihydropyrimidine dehydrogenase inactivator, and oral 5-fluorouracil with radiation therapy in patients with recurrent or advanced head and neck cancer. 1003 77

This article reviews recent literature on the physical and psychosocial correlates of head and neck cancer, with a focus on quality-of-life issues, rehabilitation outcomes, and changes in the literature from the previous decade. These studies have shown that head and neck cancer has an enormous impact on the quality of life of patients. The most important physical symptoms are speech problems, dry mouth and throat, and swallowing problems. Pain is also frequently reported. Disturbances in psychosocial functioning and psychological distress are reported by a considerable number of patients; worry, anxiety, mood disorder, fatigue, and depression are the main symptoms. Cancer of the head and neck has a negative effect on social, recreational, and sexual functioning. Despite a growing number of longitudinal studies, little is known about the rehabilitation outcomes over a longer period of time. Future research is necessary to form a consensus about the further development and use of specific instruments to study patients with cancer of the head and neck, to conduct more prospective studies, and to develop programs that are aimed at maximizing rehabilitation outcomes and evaluate these programs with randomized designs.
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PMID:Physical and psychosocial correlates of head and neck cancer: a review of the literature. 1006 50

The aim of this study was to describe prospectively quality of life and mood in patients with oral or oropharyngeal cancer treated with surgery +/- radiotherapy. Seventy-five patients completed the EORTC Core Questionnaire, the EORTC Head and Neck Cancer module and the Center for Epidemiologic Studies' Depression Scale before treatment and 6 and 12 months later. There was a significant deterioration of physical functioning, fatigue and almost all head and neck symptoms except pain, which improved. Patients with stage III/IV and patients receiving combined treatment had significantly worse physical symptoms compared to patients with stage I/II and patients treated with surgery only, respectively. Before and after treatment there was a high level of depressive symptomatology. However, after treatment a gradual improvement in emotional functioning occurred. Surgical treatment for oral or oropharyngeal cancer results in significant deterioration of physical functioning and symptoms during the first year, especially when combined with radiotherapy. Despite this, there is an improvement of emotional functioning after treatment, probably as a result of adaptation and coping processes.
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PMID:A prospective study on quality of life of patients with cancer of the oral cavity or oropharynx treated with surgery with or without radiotherapy. 1021 7

Based on the already known in vitro synergy between paclitaxel (taxol), cisplatin and oxazophosphorine cytostatics and the broad spectrum of activity of the above drugs we sought to evaluate the paclitaxel (taxol)-ifosfamide-cisplatin (PIC) combination in the outpatient setting in individuals with a variety of advanced solid tumours. Cohorts of patients were entered into six successive dose levels (DLs) with drug doses ranging as follows: paclitaxel 135-215 mg m(-2) day 1 - (1 h infusion), ifosfamide 4.5-6.0 g m(-2) (total dose) - divided over days 1 and 2, and cisplatin 80-100 mg m(-2) (total) - divided over days 1 and 2. Granulocyte colony-stimulating factor was given from day 5 to 14. Forty-two patients were entered. Eighteen patients had 2-8 cycles of prior chemotherapy with no taxanes or ifosfamide (cisplatin was allowed). The regimen was tolerated with outpatient administration in 36/42 patients. Toxicities included: grade 4 neutropenia for < or = 5 days in 27% of cycles; 5 episodes of febrile neutropenia in three patients at DL-III, -V and -VI. Grade 3/4 thrombocytopenia and cumulative grade 3 anaemia were seen in 7% and 13% of cycles respectively. Three cases of severe grade 3 neuromotor/sensory neuropathy were recorded at DL-II, -III, and -V, all after cycle 3. The maximum tolerated dose was not formally reached at DL-V, but because of progressive anaemia and asthenia/fatigue, it was decided to test a new DL-VI with doses of paclitaxel 200 mg m(-2), ifosfamide 5.0 g m(-2) and cisplatin 100 mg m(-2); this appeared to be tolerable and is recommended for further phase II testing. The response rate was 47.5% (complete response + partial response: 20/42). The PIC regimen appears to be feasible and safe in the outpatient setting. Care should be paid to neurotoxicity. Phase II studies are starting in non-small-cell lung cancer, ovarian cancer and head and neck cancer at DL-VI.
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PMID:Phase I study of dose-escalated paclitaxel, ifosfamide, and cisplatin (PIC) combination chemotherapy in advanced solid tumours. 1064 81

Patients with inoperable head and neck cancer were treated with a spleen peptide preparation (Polyerga) in a phase III randomized, placebo-controlled double-blind study during chemotherapy (cisplatin/carboplatin, 5-fluorouracil) to investigate further the efficacy of this peptide preparation as supportive treatment under chemotherapy. Immunological changes as well as quality of life aspects were examined. Forty patients were included in this study. The peptide preparation had a significant stabilizing effect on the peripheral blood lymphocyte status during chemotherapy cycles (Student t-test, p = 0.05) and tended to stabilize the shift of granulocyte count (Student t-test, p = 0.18). In addition, the group receiving the verum showed a remarkable stabilization of body weight (Mann-Whitney U-test, p = 0.17) during chemotherapy treatment and the generally observed increase of fatigue-inertia during the chemotherapy cycles was significantly reduced (Student t-test, p = 0.01).
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PMID:Effects of a spleen peptide preparation as supportive therapy in inoperable head and neck cancer patients. 1071 24

The study aim was to investigate the relationship between alcohol consumption and health-related quality of life (HRQL) in post-therapeutic head and neck cancer patients. A cross-sectional study design was used with a sample of 191 subjects. Data were collected through interview and chart review. Alcohol consumption was evaluated through the dichotomous response to the question "During the past month have you drunk alcohol on one or more occasions?" HRQL was evaluated through the EORTC QLQ-C30 and H&N35 instruments. Data were also collected concerning sociodemographic and clinical variables. Multivariate regression was used to evaluate the hypothesized association. Of 28 domains comprising the EORTC QLQ-C30 and H&N35 instruments, eight were significantly associated with alcohol consumption, while 19 of the 20 remaining domains showed a tendency towards an association. Alcohol drinking was associated with significantly better physical and role functioning, and better global HRQL, plus less fatigue, pain, problems swallowing, dry mouth and feelings of illness. This suggests that, while the study findings are limited by its design and the sample bias, despite alcohol's role as an aetiological factor, it may be reasonable to drink a little as one recovers from head and neck cancer.
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PMID:Alcohol consumption is associated with improved health-related quality of life in head and neck cancer patients. 1175 25

Cancer can cause multiple impairments, activity limitations and participation restrictions. According to individual case findings and needs, rehabilitation treatment is varied. The review mainly focuses on specific problems. Because of functional deficits cancer patients suffer from persistent emotional and social distress and a reduced quality of life (QOL). QOL encompasses at least the four dimensions of physical, emotional, social and cognitive function, which may be positively influenced by physical exercise. Physical exercise also has been shown to prevent or minimise inactivity/ disuse problems and to reduce fatigue. The management of sexuality dysfunction has to begin with a thorough history taking and a consequent sexuality counselling. The goals of rehabilitation procedures under palliative care are not only to control physical pain but also to help with mental, social and spiritual pain, together with other symptoms. Rehabilitation problems in head and neck cancer, sexuality, lung cancer, prostate cancer, breast cancer and lymphedema can be improved by rehabilitation. The review mainly focuses on impairment and activity limitation. Social, psychological and vocational aspects are left aside in this review.
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PMID:Cancer rehabilitation: particularly with aspects on physical impairments. 1289 40

Although 50-70% of head and neck cancer patients in India receive radiotherapy (RT), radiation-related acute and late morbidities and their impact on quality of life (QOL) are infrequently reported. Acute and late radiation morbidities and QOL were assessed in a prospective longitudinal study of 45 patients with head and neck cancers receiving radical RT to a dose of 7000 cGy in conventional fractionation. Grade II acute morbidities experienced by the largest percent of the sample during the course of RT pertained to the mucosa (66.4%), salivary gland (84%), and oesophagus (53%). These morbidities led to an increase in the symptom scores of appetite loss (76.46), fatigue (65.75) and pain (44.77). This increase in the symptom scores consequently led to a significant decline in physical, social and emotional functioning as well as global health status score during the course of RT (p < 0.001). Scores improved after 1 month of RT but did not reach the pre-RT value. Future studies may consider correlating QOL assessment to significant patient and disease related parameters such as performance status, weight loss, stage and site of disease.
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PMID:Radiation related morbidities and their impact on quality of life in head and neck cancer patients receiving radical radiotherapy. 1508 20

We present a laryngectomized patient with unspecific complaints of fatigue whose laboratory findings were out of proportion with the clinical presentation. The enormously high blood levels of creatine kinase (CPK) (8000 IU/l, normal range 30-190 IU/l) and thyroid-stimulating hormone (100 mU/l, normal range 0.5-4.5 mU/l) led to diagnosis and treatment of and recovery from hypothyroid myopathy. Hypothyroidism reduces the ability of the muscle to maintain its adequate energetic economy, via several suggested mechanisms. This may lead to injury (myopathy) that allows enzymes such as CPK to leak out of cells and causes elevation of their serum levels. To our knowledge, this is the first reported case of a patient previously treated for head and neck cancer who developed hypothyroid myopathy, presenting with exceptionally elevated CPK levels. This is noteworthy, since hypothyroidism may be easily avoided by a comprehensive follow-up of patients treated for head and neck cancer.
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PMID:Exceptionally elevated creatine kinase levels in a laryngectomized patient: hypothyroid myopathy. 1545 46


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