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Christina A Meyers

Publications and source records attributed to Christina A Meyers.

At least 19 recordsLinked to original sources
PubMed2006

Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors.

The inclusion of neurocognitive end points in clinical trials of patients with CNS tumors is increasing. Neurocognitive end points are used to understand what cognitive problems exist before treatment to establish a baseline by which the effect of treatment is judged, and to determine whether different treatment regimens improve neurocognitive function due to better tumor control, slow expected neurocognitive deterioration due to the tumor, or have more or less short- and long-term neurotoxicity. However, the use of neurocognitive end points in clinical trials for patients with CNS tumors is in its infancy, so that long-term outcomes are difficult to predict and the ability to determine the effects of different agents and treatment approaches is scant. Including this aspect of patient evaluation in addition to survival and time to tumor progression will yield better risk-versus-benefit assessments as well as provide a basis for improving interventions.

Central Nervous System Neoplasms↗
PubMed2006

Side-effects of chemotherapy and quality of life in ovarian and breast cancer patients.

PURPOSE OF REVIEW: Women diagnosed with ovarian cancer or breast cancer often face aggressive chemotherapy involving multiple treatment regimens. These treatments may be associated with significant side-effects that adversely impact patient quality of life. In this review, we will highlight recent research on side-effects of chemotherapy and the quality-of-life concerns of women with ovarian and breast cancer. RECENT FINDINGS: Adjuvant chemotherapy has demonstrated efficacy in the management of ovarian and breast cancers. In addition to physical side-effects, a subset of women receiving chemotherapy will experience significant cognitive dysfunction that adversely affects their perceived quality of life. Variables including disease response, treatment indication and extent of the patient's social support also influence quality-of-life ratings. SUMMARY: Although prolongation of survival remains the primary goal of chemotherapy, the palliation of symptoms and preservation of quality of life are also important treatment considerations. Chemotherapy may be associated with nausea, vomiting, hair loss, cognitive dysfunction, fatigue, changes in sexual functioning and reductions in quality-of-life ratings. Although rare to date, prospective, randomized, longitudinal studies that incorporate a pre-treatment assessment of symptom burden and perceived quality of life are necessary to define the severity and pattern of treatment-related change and subsequently guide intervention strategies. In some cases, quality-of-life issues may help to guide patient-care decisions.

Antineoplastic Agents↗
PubMed2005

Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome.

BACKGROUND: The objective of the current study was to assess the correlations between cognitive function, fatigue, quality of life, and circulating cytokine levels in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). METHODS: Fifty-four patients with AML/MDS were seen for pretreatment evaluation of their cognitive function and symptoms. Fifty percent of the sample was reevaluated 1 month later, when response to protocol chemotherapy was assessed. RESULTS: A significant proportion of patients had impaired cognitive function prior to the institution of chemotherapy. Sixty-five percent of patients also experienced significant fatigue. Levels of the circulating cytokines interleukin 1 (IL-1), IL-1 receptor antagonist (IL-1RA), IL-6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) were elevated highly compared with normal controls. Higher IL-6 levels were associated with poorer executive function, whereas higher IL-8 levels were associated with better memory performance. IL-6, IL-1RA, and TNF-alpha levels were related to ratings of fatigue. Fatigue and cognitive dysfunction were unrelated. Hemoglobin levels were not associated significantly with either cognitive dysfunction or fatigue. Patients who obtained a complete response tended to have better fine motor control at baseline and lower circulating IL-1 levels. Treatment did not have a significant impact on cognition, although fatigue levels tended to increase. CONCLUSIONS: Patients with AML/MDS are highly symptomatic and experience cognitive impairment and fatigue before the initiation of their treatment. The current results indicated a correlation between these symptoms and levels of circulating cytokines, providing some support to the hypothesis that cancer-related symptoms are related at least in part to cytokine-immunologic activation. Elucidation of immunologic correlates of symptoms will allow for targeted interventions.

Activities of Daily Living↗
PubMed2005

Neurobehavioral effects of interferon therapy.

Interferon (IFN) therapy is associated with neuropsychiatric side effects including cognitive dysfunction and mood syndromes of varying severity. These problems are the most common causes of treatment discontinuation. Dose and duration of treatment influence risk of IFN-induced side effects. Rates of IFN-induced depression vary, but approach 50% in recent studies. Presence and severity of depressive symptoms at or before treatment predicts development of mood disorders during IFN therapy. Several possible endocrine and neurotransmitter perturbations may be responsible for IFN neurotoxicity, with recent research suggesting different symptoms clusters are related to different underlying mechanisms. The interpretation of these clusters has been influenced by subjective versus objective evaluation of cognitive function. Effective management of IFN-induced neuropsychiatric side effects should involve pretreatment screening and interval assessment during therapy. Antipsychotic and psychostimulant drugs may be used against cognitive dysfunction. Antidepressants have been shown to be effective against IFN-induced depression and can be very valuable in support of adequate or completed therapy.

Antidepressive Agents↗
PubMed2004

Phase II study of fenretinide (NSC 374551) in adults with recurrent malignant gliomas: A North American Brain Tumor Consortium study.

PURPOSE: Fenretinide induces apoptosis in malignant gliomas in vitro. This two-stage phase II trial was conducted to determine the efficacy of fenretinide in adults with recurrent malignant gliomas. PATIENTS AND METHODS: Twenty-two patients with anaplastic gliomas (AG) and 23 patients with glioblastoma (GBM) whose tumors had recurred after radiotherapy and no more than two chemotherapy regimens were enrolled. Fenretinide was given orally on days 1 to 7 and 22 to 28 in 6-week cycles in doses of 600 or 900 mg/m(2) bid. RESULTS: Six of 21 (29%) patients in the AG arm and two of 23 (9%) patients in the GBM arm had stable disease at 6 months. One patient with AG treated at 900 mg/m(2) bid dosage had a partial radiologic response. Median progression-free survival (PFS) was 6 weeks for the AG arm and 6 weeks for the GBM arm. PFS at 6 months was 10% for the AG arm and 0% for the GBM arm. Grade 1 or 2 fatigue, dryness of skin, anemia, and hypoalbuminemia were the most frequent toxicities reported. The trial was closed after the first stage because of the inadequate activity at the fenretinide doses used. The first-administration mean plasma C(max) for fenretinide was 832 +/- 360 ng/mL at the 600 mg/m(2) bid dosage and 1,213 +/- 261 ng/mL at the 900 mg/m(2) bid dosage. CONCLUSION: Fenretinide was inactive against recurrent malignant gliomas at the dosage used in this trial. However, additional studies using higher doses of the agent are warranted based on the tolerability of the agent and the potential for activity of a higher fenretinide dosage, as suggested in this trial.

Administration, Oral↗
PubMed2004

'Chemobrain' in breast carcinoma?: a prologue.

BACKGROUND: Chemotherapy-induced cognitive dysfunction in patients with breast carcinoma has been described previously. However, those studies only assessed patients' postchemotherapy cognitive functioning and were not able to determine the relation between cognitive function and other treatments, such as surgery and radiotherapy, that often precede systemic chemotherapy. METHODS: Eighty-four women with breast carcinoma underwent a comprehensive neuropsychologic evaluation before receiving adjuvant therapy for nonmetastatic primary breast carcinoma. RESULTS: Before the start of systemic therapy, 35% of women in the current cohort exhibited cognitive impairment. Verbal learning (18%) and memory function (25%) were impaired significantly more frequently relative to normative expectations. Although the impairments were not significant in the women who were examined, nonverbal memory (17%), psychomotor processing speed and attention (13%), confrontational naming (13%), visuoconstruction (13%), and upper-extremity fine motor dexterity (12%) were impaired more frequently than was expected. Affective distress was related significantly to cognitive impairment (Pearson chi-square = 9.90; P = 0.002). Given the conservative statistical approach employed, extent of surgery, hormone replacement therapy history, and current menopausal status failed to achieve statistical significance, but these variables did exhibit provocative trends with respect to cognitive impairment. CONCLUSIONS: Cognitive impairment frequently is observed before the administration of systemic chemotherapy. Thus, investigations purporting to measure chemotherapy-induced cognitive dysfunction must employ study designs that incorporate prechemotherapy baseline assessments to accurately detect changes in cognitive function that are attributable to chemotherapy.

Adult↗
PubMed2004

Clinical and pharmacokinetic study of TNP-470, an angiogenesis inhibitor, in combination with paclitaxel and carboplatin in patients with solid tumors.

PURPOSE: Preclinical studies have demonstrated a synergistic effect with the angiogenesis inhibitor TNP-470 and several cytotoxic agents. A recent clinical trial with the combination of paclitaxel and TNP-470 has shown promising effects. The present study was designed to determine the toxicity and pharmacokinetics of carboplatin in combination with TNP-470 in comparison with the doublet regimen of paclitaxel and carboplatin in patients with solid tumors. EXPERIMENTAL DESIGN: Enrolled in the study were 17 patients with lung (11), head/neck (3), sarcoma (2) and thymoma (1). The patients received intravenous paclitaxel and carboplatin on day 1 followed by TNP-470 (60 mg/m(2) i.v. over 1 h administered thrice weekly on Monday, Wednesday, and Friday). Each cycle of therapy consisted of 3 weeks. The initial cohort of three patients received carboplatin at AUC 5 mg/ml x min. No dose-limiting toxic effects occurred, thus the subsequent cohort received carboplatin at AUC 6 mg/ml x min. In addition to toxicity, the pharmacokinetics of carboplatin were evaluated, and tumor response and patient survival rates were assessed. RESULTS: The administered regimen of paclitaxel (225 mg/m(2) i.v. over 3 h) and carboplatin (AUC 6 mg/ml x min i.v. over 1 h) on day 1 followed by TNP-470 (60 mg/m(2) i.v. over 1 h administered thrice weekly on Monday, Wednesday, and Friday) was defined as both the maximum tolerated and optimal dose. Hematological toxic effects were similar to those expected with the chemotherapy doublet. All neurocognitive impairments were graded as mild to moderate and reversed after discontinuation of TNP-470 administration. No alterations in the pharmacokinetic disposition of carboplatin were noted. Overall, the median survival duration was 297 days. Four patients (24%) had a partial response, and eight (47%) had stable disease. CONCLUSIONS: The combination of TNP-470, paclitaxel, and carboplatin is a reasonably well tolerated regimen. Further randomized studies of TNP-470 with this doublet regimen are now warranted for non-small-cell lung carcinoma and other solid tumors.

Adult↗
PubMed2004

The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial.

BACKGROUND: Retrospective trials have reported that chemotherapy-induced cognitive dysfunction was experienced by a subset of patients with breast carcinoma. However, recent evidence indicated that a subset also exhibited impaired cognitive function at baseline, before the start of chemotherapy. A prospective, longitudinal trial that incorporates baseline neuropsychologic evaluations is necessary to determine to what extent cognitive dysfunction is attributable to chemotherapy in this population. METHODS: Eighteen women with breast carcinoma underwent a comprehensive neuropsychologic evaluation before treatment and at short-term and long-term intervals after chemotherapy. The incidence, nature, severity, and chronicity of cognitive dysfunction developing in patients with breast carcinoma treated with a standard dose of adjuvant chemotherapy were assessed. RESULTS: Before the start of systemic therapy, 33% of women in the current cohort exhibited cognitive impairment. At the short-term postchemotherapy time point, 61% of the cohort exhibited a decline relative to baseline in 1 or more domains of cognitive functioning and reported greater difficulty in maintaining their ability to work. The most common domains of cognitive dysfunction were related to attention, learning, and processing speed. At the long-term postchemotherapy time point, approximately 50% of patients who experienced declines in cognitive function demonstrated improvement, whereas 50% remained stable. Self-reported ability to perform work-related activities also improved over this interval. Neither impairment at baseline nor subsequent treatment-related cognitive decline exhibited any statistically significant correlation with affective well-being or with demographic or clinical characteristics. CONCLUSIONS: The current study is the first longitudinal trial to report evidence of an association between cognitive dysfunction and chemotherapy in a subgroup of women with nonmetastatic breast carcinoma. The importance of using prospective research designs, appropriate cognitive measures, and statistical methods to evaluate subgroup effects was discussed. Identification of mechanisms associated with cognitive dysfunction and of risk factors contributing to subgroup vulnerability is necessary.

Adult↗
PubMed2004

Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial.

PURPOSE: To report the neurocognitive findings in a phase III randomized trial evaluating survival and neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd). PATIENTS AND METHODS: Patients were randomly assigned to receive WBRT 30 Gy in 10 fractions with or without MGd 5 mg/kg/d. Monthly neurocognitive testing for memory, executive function, and fine motor skill was performed. RESULTS: Four hundred one patients were enrolled (251 with non-small-cell lung cancer, 75 with breast cancer, and 75 with other cancers); 90.5% patients had impairment of one or more neurocognitive tests at baseline. Neurocognitive test scores of memory, fine motor speed, executive function, and global neurocognitive impairment at baseline were correlated with brain tumor volume and predictive of survival. There was no statistically significant difference between treatment arms in time to neurocognitive progression. Patients with lung cancer (but not other types of cancer) who were treated with MGd tended to have improved memory and executive function (P =.062) and improved neurologic function as assessed by a blinded events review committee (P =.048). CONCLUSION: Neurocognitive tests are a relatively sensitive measure of brain functioning; a combination of tumor prognostic variables and brain function assessments seems to predict survival better than tumor variables alone. Although the addition of MGd to WBRT did not produce a significant overall improvement between treatment arms, MGd may improve memory and executive function and prolong time to neurocognitive and neurologic progression in patients with brain metastases from lung cancer.

Adult↗
PubMed2004

A cytokine-based neuroimmunologic mechanism of cancer-related symptoms.

While many of the multiple symptoms that cancer patients have are due to the disease, it is increasingly recognized that pain, fatigue, sleep disturbance, cognitive dysfunction and affective symptoms are treatment related, and may lead to treatment delays or premature treatment termination. This symptom burden, a subjective counterpart of tumor burden, causes significant distress. Progress in understanding the mechanisms that underlie these symptoms may lead to new therapies for symptom control. Recently, some of these symptoms have been related to the actions of certain cytokines that produce a constellation of symptoms and behavioral signs when given exogenously to both humans and animals. The cytokine-induced sickness behavior that occurs in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines has much in common with the symptoms experienced by cancer patients. Accordingly, we propose that cancer-related symptom clusters share common cytokine-based neuroimmunologic mechanisms. In this review, we provide evidence from clinical and animal studies that correlate the altered cytokine profile with cancer-related symptoms. We also propose that the expression of coexisting symptoms is linked to the deregulated activity of nuclear factor-kappa B, the transcription factor responsible for the production of cytokines and mediators of the inflammatory responses due to cancer and/or cancer treatment. These concepts open exciting new avenues for translational research in the pathophysiology and treatment of cancer-related symptoms.

Cytokines↗
PubMed2004

Cognitive dysfunction and depression during treatment with interferon-alpha and chemotherapy.

Trials with interferon-alpha (IFN-alpha) have provided contradictory findings regarding the presence of cognitive side effects. The development of depression in some patients also raises questions about whether cognitive dysfunction might be secondary to an organic, interferon-induced mood disorder. Thirty patients with chronic myelogenous leukemia were examined before and during treatment with IFN-alpha alone or IFN-alpha and chemotherapy. Increased depressive symptoms and declines in information processing and executive functions were observed, but depression alone could not account for cognitive dysfunction. There was some evidence suggesting that exposure to chemotherapy and higher cumulative IFN-alpha dose may contribute to cognitive impairment.

Adult↗
PubMed2004

Depression in patients with high-grade glioma: results of the Glioma Outcomes Project.

OBJECTIVE: To study the incidence of depression among patients undergoing surgery for high-grade glioma, document factors associated with the presence of depression, and examine the relationship between depression and patient outcome. METHODS: Physician and patient reports of depression were analyzed immediately postoperatively and again 3 and 6 months after surgery for high-grade glioma. Physician-reported depression was defined according to the Diagnostic and Statistical Manual of Mental Disorders, ed 4. Patient self-assessment of depression was based on responses to questions contained in two validated functional status surveys. Concordance of physician- and patient-reported depression was examined, along with the extent of use of pharmacological treatment for depression. Additional outcomes examined included quality of life, survival, patient satisfaction, and posttreatment complications. RESULTS: Data from 598 patients were analyzed. In the early postoperative period, physicians reported depression in 15% of patients, whereas 93% of patients reported symptoms consistent with depression. The incidence of patient self-reported depression remained similar at 3- and 6-month follow-up, whereas physician reported depression increased from 15% in the early postoperative period to 22% at both 3- and 6-month follow-up. Concordance between physician recognition of depression and treatment of depression was low initially (33%) and increased at 3 and 6 months (51 and 60%, respectively). As compared with patients who were not depressed, survival was shorter and complications were more common among depressed patients. CONCLUSION: Symptoms of depression were common immediately after surgery for glioma, and they increased throughout the 6-month period after surgery. These findings support the hypothesis that clinically important depression is a common complication in patients with high-grade glioma. Concordance between physician recognition of depression and self-reports of depression by patients was low. Concordance between physician recognition of depression and initiation of pharmacological antidepressant therapy was fair in the early postoperative period and improved somewhat over the subsequent 6-month period; however, within the 6-month period after surgery for glioma, antidepressant therapy was provided for only 60% of patients in whom the physician recognized depressive symptoms and in only 15% of patients who self-reported symptoms of depression. Findings from this observational study suggest the need for a controlled trial that is designed to test the hypothesis that more attention to the identification of postoperative depression and aggressive treatment of depressive symptoms can improve the quality of life and survival of patients after surgery for high-grade glioma.

Adolescent↗
PubMed2003

Primary central nervous system lymphoma: Phase I evaluation of infusional bromodeoxyuridine with whole brain accelerated fractionation radiation therapy after chemotherapy.

BACKGROUND: The current study was performed to determine the maximum tolerated dose (MTD), toxicity, and outcome of infusional 5 bromo-2'-deoxyuridine (bromodeoxyuridine; BUdR) given with accelerated fractionation whole brain radiation therapy (WBRT) after chemotherapy for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: Twelve patients with untreated and histologically confirmed PCNSL were entered on the study between 1994 and 1996. Chemotherapy was comprised of one course of IDHAP plus high-dose methotrexate (HD-MTX). IDHAP is comprised of idarubicin at a dose of 1.5 mg/m(2)/day x 4 days intravenously by continuous infusion (i.v. CI), dexamethasone at a dose of 40 mg i.v. on Days 1-5, cytosine arabinoside at a dose of 2000 mg/ m(2) i.v. on Day 5 after cisplatin, and cisplatin at a dose of 25 mg/m(2)/day x 4 days i.v. CI. HD-MTX was given at a dose of 3.5 g/m(2) i.v. between Day 10 and Day 14 after IDHAP. BUdR was given as an i.v. CI over 48 hours, 2-3 days prior to WBRT and then weekly during WBRT. Dose escalation started at 1.5 g/m(2)/day for Cohort 1 with subsequent increments of 0.3 g/m(2)/day. The WBRT dose was 45 grays (Gy) at a dose of 1.5 Gy twice a day, 5 days per week. Neurocognitive testing was performed before, during, and after treatment. RESULTS: Nine of 12 patients entered on the study received BUdR. One of 3 patients in Cohort 1 developed leukoencephalopathy (LEP), a dose-limiting toxicity (DLT), within 2 months of the completion of therapy. Therefore, the next cohort received the same dose level. Because no toxicity was observed in Cohort 2, the third cohort received a BUdR dose of 1.8 g /m(2)/day. Shortly after completing enrollment in Cohort 3, 3 more patients developed LEP, including 2 from Cohort 1 who had received a dose of 1.5 g/m(2)/day. Thus, DLT occurred at a dose of 1.5 g/m(2)/day, the starting level in the current study. As a result, the trial was stopped. Eight of 12 patients achieved a complete response, 3 achieved a partial response, and 1 patient died before response assessment. CONCLUSIONS: Hyperfractionated WBRT with concurrent BUdR after chemotherapy was found to result in modest disease control but has unacceptable neurotoxicity.

Adult↗
PubMed2003

Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms.

BACKGROUND: Cancers and cancer treatments produce multiple symptoms that collectively cause a symptom burden for patients. These symptoms include pain, wasting, fatigue, cognitive impairment, anxiety, and depression, many of which co-occur. There is growing recognition that at least some of these symptoms may share common biologic mechanisms. METHODS: In November 2001, basic and clinical scientists met to consider evidence for a cytokine-immunologic model of symptom expression along with directions for future research. RESULTS: The characteristics of cytokine-induced sickness behavior in animal models have much in common with those of symptomatic cancer patients. Sickness behavior refers to a set of physiologic and behavioral responses observed in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines. In some cases, these responses can be prevented by cytokine antagonists. A combination of animal and human research suggests that several cancer-related symptoms may involve the actions of proinflammatory cytokines. CONCLUSIONS: Based on the similarities between cancer symptoms and sickness behavior, the authors discussed approaches to further test the implications of the relationship between inflammatory cytokines and symptoms for both symptom treatment and symptom prevention.

Animals↗
PubMed2003

Multifaceted end points in brain tumor clinical trials: cognitive deterioration precedes MRI progression.

Current treatments for brain cancer have, for the most part, equivocal survival benefit. However, clinical trials of new anticancer agents do not adequately assess potential clinical benefits for patient function other than survival and time to tumor progression. We evaluated 56 patients with recurrent brain tumors who were recruited on phase 1 and phase 2 clinical trials and given assessments of cognitive function, quality of life (QOL), and ability to perform activities of daily living (ADL) prior to receiving treatment and at intervals coinciding with MRI scans, generally monthly. Meaningful change on the cognitive and functional assessments was determined by the reliable change index. Cognitive or functional deterioration was then used as a time-dependent covariate in a Cox proportional hazards regression model with tumor progression, as defined by standard criteria, as the end point. Cognitive deterioration occurred 6 weeks prior to radiographic failure (median 7.4 weeks vs. 13.4 weeks). In contrast, median time for QOL to deteriorate was not achieved. Median time for instrumental ADL to decline was 43 weeks, long after tumor progression. For patients with brain cancer, brain function began to worsen before MRI evidence of tumor progression. QOL and ADL function were not strongly tied to cognitive decline or to time to tumor progression, suggesting that these measures may not be sufficiently sensitive to change in clinical trials of new anticancer agents, although they are important measures in terms of patient care. This study also demonstrates the feasibility of performing neurocognitive testing in this patient population. New drugs that slow the cognitive decline of brain tumor patients may be of clinical benefit regardless of the impact on overall survival.

Activities of Daily Living↗
PubMed2003

Neurocognitive and functional assessment of patients with brain metastases: a pilot study.

The outcome of patients with brain metastases is generally poor. Survival alone is not necessarily a good measure of clinical outcome. Measures of neurocognitive function and the impact of the disease and treatments on functional status also need to be considered. Although these parameters have been measured in patients with primary brain tumors, they have not been as thoroughly evaluated in patients with brain metastases. The Mini-Mental State Examination provides limited assessment of neurocognitive domains impaired in brain tumor patients. It is less sensitive to mild impairment, does not avoid memorized learning from repeat administration, and does not have validated alternative forms necessary for non-English speaking patients. To determine the feasibility of using a more comprehensive neurocognitive test battery, motor, verbal, executive, and daily functions were assessed in 30 patients with brain metastases. The test battery included the Hopkins Verbal Learning Tests, Controlled Oral Word Association Test, Grooved Pegboard Test, Trailmaking Tests A and B, and the Barthel Index. In this study, there was complete patient compliance, with average test completion time of 23 +/- 6 minutes. Despite high functional status, most patients demonstrated impairment in memory and fine motor domains. Neurocognitive test batteries can and should be used in patients with brain metastases enrolled in clinical trials.

Activities of Daily Living↗