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)

The QLQ-C30, a health-related quality of life questionnaire developed for use in patients with cancer, has been previously validated in patients with lung cancer and head and neck cancer. In this study, further validation was carried out for 535 patients, including patients with breast cancer (n = 143) and ovarian cancer (n = 111) for whom there is no previously published validation, as well as patients with lung cancer (n = 160) and a heterogeneous group of other cancers (n = 121). All patients were entered in one of two trials of anti-emetics to prevent chemotherapy-induced emesis. The QLQ-C30 was completed before chemotherapy and on day 8 after chemotherapy. The factor structure in patients with breast and ovarian cancer was similar to that previously described. Interdomain correlations, in the entire group, were strongest for the physical and role function domains and the fatigue, pain and global quality of life domains before and after chemotherapy. In addition, after chemotherapy, social function was also strongly correlated with fatigue and global quality of life. These correlations were not always of equal strength in the breast, ovarian and lung groups, suggesting that there may be differences between these groups. The responsiveness of the QLQ-C30 in the presence of widely metastatic, as compared with locoregional, disease showed changes in the expected directions (i.e., diminished function in physical and social role functions and in global quality of life, with greater fatigue and pain in patients with metastatic disease). Eight days after chemotherapy, decreases were seen in physical, role and social functioning and in global quality of life, and there was greater fatigue, nausea and vomiting compared with before chemotherapy. Patients with breast cancer had better physical, role and social functioning and less fatigue and pain than patients with ovarian cancer. This result is expected, since many of the patients with breast cancer had early stage disease, whereas those with ovarian cancer had advanced stage disease. Mean scores for patients with lung cancer were between the other two groups, in keeping with the mixture of early and advanced stage disease in these patients. There was a strong correlation between ECOG performance status scores and several domains of the QLQ-C30; these were all in the expected directions. The results of this study confirm those in earlier studies on patients with lung cancer, and provide new information on patients with breast and ovarian cancer. In addition, the QLQ-C30 is responsive to the effects of chemotherapy and of metastatic disease.
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PMID:Psychometric properties and responsiveness of the EORTC quality of Life Questionnaire (QLQ-C30) in patients with breast, ovarian and lung cancer. 784 68

Taxol is a novel taxane derivative obtained from the bark of the Pacific yew, Taxus brevifolia, which has demonstrated substantial antitumor activity in early clinical trials. Intensive research efforts were necessary to overcome both supply problems and hypersensitivity reactions to the drug and thus assure its widespread use. Taxol is active in a variety of neoplasias, including advanced breast and ovarian tumors resistant to drugs such as doxorubicin and cisplatin, respectively. We report here the initial experience with taxol in these two disease entities in Israel, at three institutions within the framework of large multinational trials. These studies compared a) the use of two dose levels of taxol, and b) short, 3-h administration vs. a longer 24-h infusion of the drug. A total of 107 Israeli patients, 38 with ovarian cancer and 69 with breast cancer, were given 706 courses of taxol. Our results show that the administration of taxol at doses ranging between 135 and 175 mg/m2 is indeed feasible and that 3-h infusions are as well tolerated as longer administration. The main hematological toxicity was leukopenia, which was promptly reversible and was more pronounced both at the higher dose level and with the more prolonged infusion. Of the nonhematological side effects, the most prominent were alopecia, mild nausea and vomiting, limb paresthesias, fatigue and myalgia. Allergic reactions following routine premedication were mild and infrequent, never necessitating discontinuation of the drug. Clinically significant cardiac events did not occur. Taxol is an important addition to the anticancer chemotherapy armamentarium.
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PMID:Taxol: initial Israeli experience with a novel anticancer agent. 790 13

Despite the importance of symptom control in the cancer population, few studies have systematically assessed the prevalence and characteristics of symptoms or the interactions between various symptom characteristics and other factors related to quality of life (QOL). As part of a validation study of a new symptom assessment instrument, inpatients and outpatients with prostate, colon, breast or ovarian cancer were evaluated using the Memorial Symptom Assessment Scale and other measures of psychological condition, performance status, symptom distress and overall quality of life. The mean age of the 243 evaluable patients was 55.5 years (range 23-86 years); over 60% were women and almost two-thirds had metastatic disease. The Karnofsky Performance Status (KPS) score was < or = 80 in 49.8% and 123 were inpatients at the time of assessment. Across tumour types, 40-80% experienced lack of energy, pain, feeling drowsy, dry mouth, insomnia, or symptoms indicative of psychological distress. Although symptom characteristics were variable, the proportion of patients who described a symptom as relatively intense or frequent always exceeded the proportion who reported it as highly distressing. The mean (+/- SD range) number of symptoms per patient was 11.5 +/- 6.0 (0-25); inpatients had more symptoms than outpatients (13.5 +/- 5.4 vs. 9.7 +/- 6.0, p < 0.002) and those with KPS < or = 80 had more symptoms than those with KPS > 80 (14.8 +/- 5.5 vs. 9.2 +/- 4.9, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Symptom prevalence, characteristics and distress in a cancer population. 792 Apr 92

21 untreated ovarian cancer patients with stage III and minimal tumour size, were given weekly intraperitoneal (i.p.) carboplatin (150 mg/m2) and alpha-2b interferon (IFN) (30 million U/m2) for a total of 12 courses, from June 1989 to February 1993. To date, a total of 248 courses have been administered. Toxicity was seldom severe, although fever (179 courses), fatigue (141 courses) and other IFN-related side-effects were very frequent. No patient refused to continue treatment, but in 5 patients IFN dose had to be reduced, and in 1 it was discontinued. The IFN mean delivered dose intensity was 19.8 million U/m2 week. Grade 3-4 myelotoxicity occurred in 7 patients (39 courses), but no deaths related to treatment occurred. The actual mean dose intensity of carboplatin was 121.5 mg/m2 week. To date, 20 patients have completed treatment and are evaluable for response. Of 11 patients with tumour size < or = 5 mm, 10 (91%) achieved a pathological complete response (pCR) as did 4/9 (44%) of those with tumour > 5 mm at entry, for a 70% (95% confidence interval 50-90) overall pCR rate. At a median follow-up of 21 months (range 4-46), only one death occurred. The probability of being alive at almost 4 years was 91% in the entire group (100% in those with tumour size less than 5 mm). Only 1 of 14 patients who achieved a pCR relapsed. This i.p. combination seems a feasible approach to previously untreated ovarian cancer patients with minimal tumour burden. IFN dosage should be reduced to improve tolerance. In view of the very high pCR rate achieved in the group of patients with smaller tumours, a randomised trial is warranted to compare this approach to standard treatment in these patients.
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PMID:Carboplatin and alpha-2b interferon intraperitoneal combination as first-line treatment of minimal residual ovarian cancer. A pilot study. 794 89

The Memorial Symptom Assessment Scale (MSAS) is a new patient-rated instrument that was developed to provide multidimensional information about a diverse group of common symptoms. This study evaluated the reliability and validity of the MSAS in the cancer population. Randomly selected inpatients and outpatients (n = 246) with prostate, colon, breast or ovarian cancer were assessed using the MSAS and a battery of measures that independently evaluate phenomena related to quality of life. Symptom prevalence in the 218 evaluable patients ranged from 73.9% for lack of energy to 10.6% for difficulty swallowing. Based on a content analysis, three symptoms were deleted and two were added; the revised scale evaluates 32 physical and psychological symptoms. A factor analysis of variance yielded two factors that distinguished three major symptom groups and several subgroups. The major groups comprised psychological symptoms (PSYCH), high prevalence physical symptoms (PHYS H), and low prevalence physical symptoms (PHYS L). Internal consistency was high in the PHYS H and PSYCH groups (Cronback alpha coefficients of 0.88 and 0.83, respectively), and moderate in the PHYS L group (alpha = 0.58). Although the severity, frequency and distress dimensions were highly intercorrelated, canonical correlations and other analyses demonstrated that multidimensional assessment (frequency and distress) augments information about the impact of symptoms. High correlations with clinical status and quality of life measures support the validity of the MSAS and indicate the utility of several subscale scores, including PSYCH, PHYS, and a brief Global Distress Index. The MSAS is a reliable and valid instrument for the assessment of symptom prevalence, characteristics and distress. It provides a method for comprehensive symptom assessment that may be useful when information about symptoms is desirable, such as clinical trials that incorporate quality of life measures or studies of symptom epidemiology.
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PMID:The Memorial Symptom Assessment Scale: an instrument for the evaluation of symptom prevalence, characteristics and distress. 799 21

Forty-one ovarian cancer patients with less than 2 cm residual disease after systemic cisplatin-based chemotherapy received 4 courses of an ip regimen including cisplatin (75 mg/m2), mitoxantrone (20 mg/m2), and interferon-alpha 2b (30 mil IU/m2). The most important side effects were abdominal pain and fatigue. Overall 15/41 patients (37%) required narcotic analgesia for severe abdominal pain. In 1 case laparotomy was necessary due to bowel obstruction. Grade 3-4 myelotoxicity was observed in 18/41 patients (28 courses). No treatment-related death occurred. Pathological complete response (pCR) was achieved in 23/37 (62%) evaluable patients. Four-year disease-free survival was 50%, and no relapse occurred after 32 months. The estimated 4-year progression-free survival (PFS) and overall survival were 35 and 60%, respectively. Patients who achieved pCR showed significantly better survival than the others (P < 0.000). At multivariate Cox's analysis pCR achievement was the most important predictor of PFS (P < 0.005) and survival (P < 0.02). Age (< or = 60 vs > 60) and CA-125 serum levels at entry (normal vs increased) also showed independent predictive value. On the basis of multivariate analysis results we created a risk model for survival and PFS based on age and CA-125 at entry. We identified three subgroups of patients with significantly different outcomes. With this new ip combination long-term disease-free survival is achieved in a significant part of ovarian cancer patients with small tumor burden. A longer follow-up is needed to see whether it can cure some of these patients, and further comparisons with other ip or systemic regimens are needed to draw definitive conclusions about its role in these patients.
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PMID:Intraperitoneal (ip) cisplatin-mitoxantrone-interferon-alpha 2b in ovarian cancer patients with minimal residual disease. 834 66

Manganese superoxide dismutase (SOD2) converts superoxide to oxygen plus hydrogen peroxide and serves as the primary defense against mitochondrial superoxide. Impaired SOD2 activity in humans has been associated with several chronic diseases, including ovarian cancer and type I diabetes, and SOD2 overexpression appears to suppress malignancy in cultured cells. We have produced a line of SOD2 knockout mice (SOD2m1BCM/SOD2m1BCM) that survive up to 3 weeks of age and exhibit several novel pathologic phenotypes including severe anemia, degeneration of neurons in the basal ganglia and brainstem, and progressive motor disturbances characterized by weakness, rapid fatigue, and circling behavior. In addition, SOD2m1BCM/SOD2m1BCM mice older than 7 days exhibit extensive mitochondrial injury within degenerating neurons and cardiac myocytes. Approximately 10% of SOD2m1BCM/SOD2m1BCM mice exhibit markedly enlarged and dilated hearts. These observations indicate that SOD2 deficiency causes increased susceptibility to oxidative mitochondrial injury in central nervous system neurons, cardiac myocytes, and other metabolically active tissues after postnatal exposure to ambient oxygen concentrations. Our SOD2-deficient mice differ from a recently described model in which homozygotes die within the first 5 days of life with severe cardiomyopathy and do not exhibit motor disturbances, central nervous system injury, or ultrastructural evidence of mitochondrial injury.
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PMID:Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. 879 Apr 8

Thirty-eight women with epithelial ovarian cancer were treated with gemcitabine, a new antimetabolite. All had previously received platinum, and 27 had also received paclitaxel. Four patients had a partial response giving a response rate of 13% in assessable patients (n = 31) and 11% for all patients entered. Additionally, 6 patients had stable disease with >50% reduction in CA-125 for at least 3 months. Activity was seen in patients resistant to both platinum and paclitaxel. Gemcitabine was well tolerated, with uncomplicated neutropenia the main hematological toxicity. Nonhematological toxicities were generally mild and included fatigue, myalgias, and skin rash. Gemcitabine has some activity in heavily pretreated ovarian cancer patients and deserves further investigation in this malignancy.
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PMID:Activity of gemcitabine in patients with advanced ovarian cancer: responses seen following platinum and paclitaxel. 889 75

A combination of platinum and a taxane is regarded by many as the optimum treatment for advanced epithelial ovarian carcinoma. A recent meta-analysis has suggested that the addition of an anthracycline to platinum-based chemotherapy is associated with a significant survival advantage. We are therefore conducting an ongoing phase I/II study combining drugs from these three classes. We report here the first phase using carboplatin at an area under the concentration-time curve of 7, doxorubicin 50 mg/m2, and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 over 3 hours. The treatment was given on a 3-weekly cycle and granulocyte colony-stimulating factor was given if the nadir neutrophil count fell below 0.5 x 10(9)/L and was continued until recovery. Toxicity was assessed according to the Common Toxicity Criteria. All patients were required to have advanced ovarian cancer (stage IC to IV) but be ineligible for standard chemotherapy trials or to have advanced gynecologic malignancy, such as mixed mullerian tumor, fallopian tube carcinoma, coelomic carcinoma, or primary peritoneal carcinoma. To date, seven patients have been treated, and all were of performance status 0 to 2, 18 to 70 years old, with a life expectancy of > or = 3 months. Hematologic toxicity was significant, with all patients having grade 3/4 thrombocytopenia and six of seven grade 3/4 leukopenia. There was, however, only one grade 3/4 infection. Three patients have experienced fatigue, which in two cases was severe, and one patient had grade 3/4 stomatitis. Dose reduction was due to myelosuppression and was required in five patients. Five patients were evaluable for response, all of whom have obtained complete or partial response. There has been no clinical evidence of cardiotoxicity, but four patients had grade 1/2 cardiotoxicity as measured by left ventricular ejection fraction. We conclude that this combination is active and has acceptable but significant toxicity. It is only suitable for very fit patients, and we are currently assessing ways of reducing toxicity.
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PMID:Taxane/platinum/anthracycline combination therapy in advanced epithelial ovarian cancer. 904 34

There has been little investigation of the side-effects experienced by women receiving adjuvant carboplatin in the treatment of ovarian cancer. This study aimed to describe the range of problems experienced by patients and to estimate incidence and severity of side-effects over the treatment period. Eleven patients participated and completed a 75-item self-report questionnaire at each course of treatment. Severity of each side-effect was graded from 0 to 4. Patients also stated which had been the worst side effect at each course. The response rate was 94%. Seventy-two side-effects were reported. Fatigue emerged as both the most common and the most 'troublesome' side-effect. Nausea, difficulty sleeping, taste change, and constipation were also ranked highly. Although limited by a small sample size, this study suggests patients undergoing carboplatin experience a wide range of problems, many of which merit further investigation.
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PMID:Patients' experiences of chemotherapy: side-effects of carboplatin in the treatment of carcinoma of the ovary. 923 31


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