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Biomedical subjects

G Curt

Publications and source records attributed to G Curt.

12 recordsLinked to original sources
PubMed2001

Cancer-related fatigue: prevalence of proposed diagnostic criteria in a United States sample of cancer survivors.

PURPOSE: To evaluate the proposed cancer-related fatigue (CRF) diagnostic criteria in a sample of cancer survivors. More accurate prevalence estimates of CRF may result in improved diagnosis and management of one of the most common symptoms associated with cancer and its treatment. METHODS: Three hundred seventy-nine individuals who had been treated with chemotherapy, either alone or in combination with radiation therapy, were surveyed. Patients were asked background questions about their current condition, their medical history, and the frequency of fatigue during their chemotherapy. Additionally, patients who reported experiencing fatigue at least a few days each month during treatment were asked a series of questions about the impact of fatigue on their daily functioning. RESULTS: One hundred forty-one (37%) individuals reported at least 2 weeks of fatigue in the previous month. Of the respondents who had received their last treatment more than 5 years ago, 33% still reported at least a 2-week period of fatigue in the month before the interview. Evaluation of the proposed criteria revealed that 17% of respondents met at least two criteria for CRF. CONCLUSION: The prevalence of diagnosable CRF in the individuals in this sample, most of whom had completed treatment more than 1 year ago, was 17%-lower than expected based on previous reports that have used less-strict criteria. In a sizable number of people, CRF persists well beyond active treatment and should be a focus of intervention. Although they will require replication in other samples and clinical validation, these formal diagnostic criteria can be a step toward common language and a better understanding of the severity range and persistence of CRF.

Data Collection↗
PubMed2000

Use of complementary medicine by adult patients participating in HIV/AIDS clinical trials.

OBJECTIVE: To identify and characterize patterns of use of complementary and alternative (CAM) therapies by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients participating in clinical trials in a research setting. DESIGN: A descriptive survey using a nonrandom sample of 100 patients was conducted over 17 months, using a 99-item interview schedule adapted from a previous study. SETTING: National Institutes of Health (NIH) Warren G. Magnuson Clinical Center. SUBJECTS: Patients diagnosed with HIV/AIDS, participating in clinical research protocols at the National Institute of Allergy and Infectious Diseases and the National Cancer institute (NCI) at the NIH. RESULTS: Ninety-one percent (91%) had used at least one CAM therapy, as defined by a 1993 study by Eisenberg et al., sometime in their lives. Postdiagnosis, 84% used at least one CAM therapy with an average of just fewer than 5. The increase in frequency of use from 64% prediagnosis was significant (P2 = 0.019). Therapies that became significantly more popular postdiagnosis were, imagery (P2 = 0.00012), high-dose vitamins, (P2 = 0.000019), weight gain (p2 = 0.000244), massage (p2 = 0.00091), relaxation (p2 = 0.0033), herbals (p2 = 0.013), spiritual (p2 = 0.024), and acupuncture (p2 = 0.035). They were primarily used for HIV/AIDS-related problems: dermatological, nausea, depression, insomnia, and weakness. There was a high level of agreement that benefits of CAM use were: feeling better, 51 (98.1%), increased coping, 52 (100%), feeling in control, 44 (88.5%), and enhanced treatment outcome, 49 (94.2%) with 32 (61%) stating CAM was as, or more effective than conventional treatment. Fifty-three percent (53%) were specifically asked by physicians whether they were using adjunct therapies. CONCLUSIONS: Subjects used a variety of CAM therapies to cope with their diseases and rigors of treatment and clinical trials. Further research is needed to identify CAM therapies that may be used as adjunct treatments during clinical trials.

Adult↗
PubMed2000

Use of complementary medicine by adult patients participating in cancer clinical trials.

PURPOSE/OBJECTIVES: To document the prevalence, demographic correlates, patterns of use, and beliefs about complementary and alternative medicine (CAM) therapies of adult patients enrolled in National Cancer Institute (NCI) clinical trials. DESIGN: Prospective, cross-sectional, descriptive survey. SETTING: W.G. Magnuson Clinical Center of the National Institutes of Health in Bethesda, MD. SAMPLE: Convenience sample of 100 English-speaking, adult patients with cancer admitted to intramural clinical trials. METHODS: A standardized, 99-item questionnaire assessing use of CAM therapies pre- and postcancer diagnosis was administered by face-to-face interview. MAIN RESEARCH VARIABLES: Use of CAM therapies, beliefs, communication with physician. FINDINGS: 63% used at least one CAM therapy, with an average use of two therapies per patient. Men were significantly less likely to use a therapy than women; women were more likely to use numerous therapies. Cancer diagnosis seems to have had no influence overall on the frequency of use of CAM therapies. The major reasons stated for CAM use were for treatment-related medical conditions as well as depression, anxiety, and insomnia. The most frequently reported therapies were spiritual, relaxation, imagery, exercise, lifestyle diet (e.g., macrobiotic, vegetarian), and nutritional supplementation. Patients unanimously believed that these complementary therapies helped to improve their quality of life through more effective coping with stress, decreasing the discomforts of treatment and illness, and giving them a sense of control. CONCLUSIONS: Patients with cancer use various complementary therapies to cope with their disease and the rigors of clinical trials. Women and those with higher educational backgrounds were more frequent users. IMPLICATIONS FOR NURSING PRACTICE: Nurses who provide care to subjects of biomedical research have an opportunity and responsibility regarding their patients' use of CAM therapies. Nurses may use in-house resources to help evaluate subjects' use of a CAM modality or to provide quality-of-life therapies such as relaxation, imagery, or healing touch. Discussing these health practices in a nonjudgmental manner adds to the assessment of patients' coping skills and ability to make decisions about their health care.

Adaptation, Psychological↗
PubMed1997

Genistein-induced apoptosis of prostate cancer cells is preceded by a specific decrease in focal adhesion kinase activity.

Genistein (5,7,4'-trihydroxyisoflavone), an isoflavinoid found in soy beans, has been identified as potentially causal for the low incidence of metastatic prostate cancer (PCa) in certain countries. Although genistein-induced PCa cell adhesion has been identified as a possible causative mechanism, direct growth inhibition by genistein has been reported and also could be causal. If in vivo growth inhibition was significant, then growth inhibition should occur at concentrations attained with dietary consumption, the mechanism of growth inhibition should be relevant to PCa, and genistein (a broad-spectrum in vitro protein-tyrosine kinase inhibitor) should have relatively specific kinase inhibitory effects in vivo. These considerations were investigated by measuring growth inhibitory activity in a variety of PCa cell lines. Growth inhibitory effects were shown not to occur with concentrations below the low micromolar range (i.e., 3 logs above that attained in serum). In-depth mechanistic studies with the PC3-M metastatic variant cell line demonstrated that growth inhibition was independent of genistein's estrogenic effects. Genistein was shown to decrease the viability of nonadherent cells, suggesting a lack of dependence on cell adhesion for growth inhibition. However, important molecular and kinetic differences between genistein's effects on growth in adherent versus nonadherent cells were identified. Specific suppression of focal adhesion kinase activity (without global decreases in phosphotyrosine) was shown to precede induction of apoptosis, which was responsible for growth inhibition in adherent cells. These findings do not support an in vivo growth inhibitory role by genistein consumed in quantities associated with a soy-based diet. They do, however, identify genistein as a potential therapeutic agent for PCa and as a tool with which to study the control of apoptosis in PCa.

Apoptosis↗
PubMed1996

Phase I trial of iodine 131-labeled COL-1 in patients with gastrointestinal malignancies: influence of serum carcinoembryonic antigen and tumor bulk on pharmacokinetics.

PURPOSE: COL-1 is a high-affinity murine monoclonal antibody (MAb) specific for carcinoembryonic antigen (CEA). A phase I trial was conducted in which a uniform quantity of antibody labeled with escalating doses of iodine 131 (131I) was administered to patients with advanced gastrointestinal (GI) malignancies to evaluate tolerance and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients with advanced, assessable GI malignancies (16 colon, one pancreas, and one gastric) previously treated with conventional chemotherapy (but no pelvic radiation) received 20 mg of COL-1 labeled with 131I, with doses from 10 mCi/m2 to 75 mCi/m2. In this cohort, the baseline serum CEA level ranged from 6 to 2,739 ng/mL (mean +/- SD, 500 +/- 639). RESULTS: Nuclear imaging detected at least one tumor site in all 18 patients; 82% of all tumor involved organs were positive and 58% of all lesions > or = 1.0 cm were detected. Immune complexes were detected in 89% of patients 5 minutes after completion of infusion, and levels correlated with CEA levels (r = .71). Elevated CEA (> 500 ng/mL) and tumor bulk (total tumor area > 150 cm2) correlated directly with clearance of serum radioactivity and inversely with serum half-life and cumulative serum radioactivity parameters. Nonhematologic toxicity was mild and non-dose-limiting. Hematologic toxicity, particularly thrombocytopenia, was both dose-related and dose-limiting. The maximal-tolerated dose is 65 mCi/m2. The correlation between dose (millicuries per square meter) and thrombocytopenia was made stronger, by accounting for either variation in pharmacokinetics, or variation in serum CEA and tumor bulk. CONCLUSION: 131I-COL-1 is well tolerated, except for hematologic toxicity. These data suggest that patients with highly elevated circulating CEA levels and/or increased tumor bulk may clear 131I-labeled COL-1 more rapidly from the circulation and experience less myelosuppression.

Antibodies, Monoclonal↗
PubMed1995

Phase I study of intravenous Lu-labeled CC49 murine monoclonal antibody in patients with advanced adenocarcinoma.

CC49, a murine monoclonal antibody that recognizes the tumor-associated glycoprotein 72, was conjugated to the chemical chelate 1,4,7,10-tetraaza-1-(1-carboxy-3-(4-aminophenyl) propyl)-tris-4,7,10- ((carboxy)methyl)cyclododecane that had been labeled with a beta emitter, Lu. Preclinical studies had shown that Lu-labeled CC49 caused regression of human colon adenocarcinoma xenografts in nude mice. Patients with advanced adenocarcinoma who had failed standard treatment and whose tumors expressed the tumor-associated glycoprotein 72 antigen were eligible for treatment to determine the maximum tolerated dose of Lu-labeled CC49. The starting dose of Lu was 10 mCi/m2 given i.v. with the dose of CC49 held constant at 20 mg. Pharmacokinetic sampling and immunoscintigraphy were performed over the ensuing 3 weeks. The dose of radioactive Lu was escalated by 15 mCi/m2 for each successive dose level. Unexpected bone marrow toxicity developed in patients treated at the second dose level with 25 mCi/m2 Lu; two patients developed grade 4 thrombocytopenia, while the third patient developed grade 3 thrombocytopenia. Pharmacokinetic studies showed that the plasma half-life of the immunoconjugate was 67 h; whole-body retention, however, was prolonged with a biological half-life of 258 h. Serial gamma camera imaging localized known tumor in all patients, and also demonstrated prolonged Lu retention in the reticuloendothelial system (RES). Bone marrow dosimetry estimates ranged from 4 to 5 REMS/mCi Lu based on imaging and biopsy data. Analysis of bone marrow biopsies demonstrated that most of the Lu was localized in the cellular compartment and not in the bone. No antitumor responses were observed. Intravenous administration of 15 mCi/m2 Lu-labeled CC49 to previously treated advanced cancer patients was associated with acceptable hematological toxicity and was the maximum tolerated dose. However, prolonged retention of Lu in the RES, including the bone marrow, was observed and limited the dose of Lu that could be given. Additional studies are indicated to reduce RES uptake and retention of this immunoconjugate.

Adenocarcinoma↗
PubMed1990

Oral zidovudine, continuous-infusion fluorouracil, and oral leucovorin calcium: a phase I study.

A phase I clinical, pharmacologic, and biochemical evaluation of escalating oral zidovudine (AZT) given over 2 days with a fixed dose of continuous-infusion fluorouracil (800 mg/m2 per day X 3 days) and oral leucovorin calcium was performed. Eighteen patients were treated with doses of AZT ranging from 1.0 to 9.0 g/m2 per day. Nausea and vomiting were dose limiting, with a maximally tolerated dose of 7.5 g/m2 per day. Rash and mucositis occurred but were not dose limiting. A dose-related increase in peak plasma levels of AZT was observed, and the alpha half-life of AZT in plasma (75 min) was unaffected by these high doses. At doses above 4.0 g/m2 per day, trough levels significantly increased, perhaps reflecting prolonged absorption from the gut. No responses were observed; however, a significant increase in DNA single-strand breaks was observed in peripheral blood cells after a threshold dose of 4.0 g/m2 per day, confirming a biological effect of AZT in this regimen. Further trials with an intravenous formulation capable of maintaining plasma levels and circumventing dose-limiting toxicity are warranted.

Administration, Oral↗
PubMed1990

A phase I-II trial of continuous-infusion cisplatin, continuous-infusion 5-fluorouracil, and VP-16 in colorectal carcinoma.

Twenty-nine evaluable patients with colorectal adenocarcinoma were treated in a phase I-II trial of combination chemotherapy with a 72-h continuous infusion of cisplatin (CDDP) and 5-fluorouracil (5-FU) with an infusion of VP-16 given at 24 and 48 h after the start of therapy. There were five (17 +/- 14%) partial responses lasting 2-6 months (median, 3). Three of these responses occurred among the 10 previously untreated patients. The toxicity of this regimen was pronounced. Four of eight patients with severe neutropenia required hospitalization for infections, two of which were life-threatening; one of six patients with severe thrombocytopenia had a life-threatening hemorrhagic complication; and four patients experienced severe, dose-limiting fatigue. These complications occurred principally with CDDP and VP-16 at doses above 27.5 mg/m2/day and 110 mg/m2/dose, respectively. Mucositis occurred in six patients and limited the dose of 5-FU to 1,300 mg/m2/day. Although the response rate appeared to be high in previously untreated patients, the minimal palliative benefit of treatment and the brief duration of the responses do not compensate for the toxicity observed.

Adenocarcinoma↗
PubMed1987

High-dose carboplatin in refractory ovarian cancer patients.

Thirty previously treated refractory ovarian cancer patients, all of whom received prior therapy with cisplatin, were treated in a phase II trial with high-dose carboplatin (800 mg/m2 per cycle with cycles administered every 35 days). Patients were treated with high-dose carboplatin when they were no longer responding to prior therapy or had relapsed after an initial response. Objective responses were achieved in eight of 30 patients (27%) while ten patients had minor responses or stable disease. No responses were observed from high-dose carboplatin in patients who had progressive disease during prior therapy with a cisplatin-based regimen. The primary toxicity of high-dose carboplatin was myelosuppression with a median WBC nadir of 0.6 and a median platelet nadir of 6,500 after the first cycle of therapy. Myelosuppression was not particularly cumulative as 78% of patients were able to receive either 100% or 75% of the projected dose even with the fourth cycle of high-dose carboplatin. The gastrointestinal (GI) toxicity of carboplatin was mild and there was no clinically apparent nephrotoxicity or neurotoxicity. These results demonstrate that: there is marked cross-resistance between cisplatin and carboplatin, and high-dose carboplatin may be a potential alternative to high-dose cisplatin in the treatment of ovarian cancer patients.

Adult↗
PubMed1985

A phase I and pharmacology study of continuous-infusion low-dose methotrexate administration.

Continuous intravenous infusion of methotrexate (MTX) was evaluated in a Phase I study designed to establish the optimal dose rate to provide a minimum of 28 days of constant 24-hour drug exposure. Twenty-six courses were administered to 21 patients at dose rates of 0.75 mg/M2/day to 3 mg/M2/day. Dose-limiting toxicity was predominantly stomatitis at the highest dose rates. Thrombocytopenia (platelet count less than 100,000) without leukopenia developed in 8 of 26 courses at the lower dose rates, with or without stomatitis, and was rapidly reversible. Serial blood levels revealed detectable serum MTX concentrations at all dose rates delivered with mean MTX concentrations varying from 12.8 nM at 0.75 mg/M2/day to 140 nM at 2.5 mg/M2/day. Total-body clearance of MTX approximated renal creatinine clearance. The recommended dose rate for continuous infusion of methotrexate is 0.75 mg/M2/day for 28 days, and for shorter durations (less than or equal to 14 days), the optimal dose rate is 1.5 mg/M2/day. The continuous-infusion schedule for MTX, therefore, results in a substantial decrease in the delivered dose compared with that achieved with a bolus schedule.

Adult↗
PubMed1985

5-Fluorouracil and methotrexate administered simultaneously as a continuous infusion. A phase I study.

Infusion delivery systems have been evaluated for administration of many individual chemotherapeutic agents including 5-fluorouracil (5-FU) and methotrexate (MTX). This study combined the two drugs as an admixture, and in a Phase I trial design established a useful dose schedule for each of the component drugs. 5-FU at a fixed dose rate of 300 mg/M2/day was delivered with methotrexate (MTX) at four different dose rates (0.75, 1.0, 1.5, or 2.0 mg/M2/day, respectively). The drug solution was delivered via a subclavian venous access with a portable infusion pump in an ambulatory setting. Twenty-nine patients received a total of 38 courses of the two-drug infusion: 21 courses were delivered with the two agents admixed constantly throughout treatment (Schedule A) and 17 were administered the treatment with 5-FU delivered continuously and MTX added to the 5-FU for alternate 14-day cycles (Schedule B). For the former schedule, dose-rate-limiting toxicity was related to MTX and included stomatitis developing at days 8 to 14 (median, day 8) with the higher dose rates (1.5-2.0 mg/M2/day) and thrombocytopenia developing at days 11 to 56 (median, day 14) at the lowest dose rates (1.0 mg/M2/day). For Schedule B, dose-rate-limiting toxicity was similarly due to the MTX with thrombocytopenia and/or chemical hepatitis developing in six of seven courses of MTX at 1.0 mg/M2/day and in five of ten courses delivered at 0.75 mg/M2/day. On Schedule B the MTX-associated toxicities were reversed when the MTX administration was interrupted and in the face of continued 5-FU infusion. A reasonable dose rate and schedule for continuous infusion of 5-FU combined with MTX is: 5-FU 300 mg/M2/day X 28 days and MTX 0.75 mg/M2/day for days 1 to 14, with cycles administered consecutively each 28 days.

Adult↗