The use of Ginkgo biloba for the prevention of chemotherapy-related cognitive dysfunction in women receiving adjuvant treatment for breast cancer, N00C9.

PURPOSE: Patients undergoing treatment for cancer often report problems with their cognitive function, which is an essential component of health-related quality of life. Pursuant to this, a two-arm randomized, placebo-controlled, double-blind, phase III clinical trial was conducted to evaluate Ginkgo biloba (EGB 761) for the prevention of chemotherapy-related cognitive dysfunction in patients with breast cancer. METHODS: Previously chemotherapy naïve women about to receive adjuvant chemotherapy for breast cancer were randomized to receive 60 mg of EGB 761 or a matching placebo twice daily. The study agent was to begin before their second cycle of chemotherapy and to be taken throughout chemotherapy and 1 month beyond completion. The primary measure for cognitive function was the High Sensitivity Cognitive Screen (HSCS), with a secondary measure being the Trail Making Tests (TMT) A and B. Subjective assessment of cognitive function was evaluated by the cognitive subscale of the Perceived Health Scale (PHS) and the Profile of Mood States (POMS). Data were collected at baseline and at intervals throughout and after chemotherapy, up to 24 months after completion of adjuvant treatment. The primary statistical analysis included normalized area under the curve (AUC) comparisons of the HSCS, between the arms. Secondary analyses included evaluation of the other measures of cognition as well as correlational analyses between self-report and cognitive testing. RESULTS: One hundred and sixty-six women provided evaluable data. There were no significant differences in AUC up to 12 months on the HSCS between arms at the end of chemotherapy or at any other time point after adjuvant treatment. There were also no significant differences in TMT A or B at any data point. Perceived cognitive functions, as measured by the PHS and confusion/bewilderment subscale of the POMS, were not different between arms at the end of chemotherapy. There was also little correlation between self-reported cognition and cognitive testing. No differences were observed in toxicities per Common Terminology Criteria for Adverse Events (CTCAE) assessment between Ginkgo biloba and placebo throughout the study; however, after chemotherapy, the placebo group reported worse nausea (p = .05). CONCLUSION: This study did not provide any support for the notion that Ginkgo biloba, at a dose of 60 mg twice a day, can help prevent cognitive changes from chemotherapy. These analyses do provide data to further support the low associations between patients' self-report of cognition and cognitive performance, based on more formal testing.

Longitudinal cognitive function and brain metabolites in women receiving chemotherapy for stage 1 to 3 breast cancer: Observational study.

Few proton magnetic resonance spectroscopy studies have explored chemotherapy-related biochemical changes in brain regions. This observational study aimed to longitudinally assess short-term cognitive changes and brain metabolite concentrations in women undergoing chemotherapy for breast cancer. We analyzed 11 women with newly diagnosed stage 1 to 3 breast cancer. Patients were evaluated via objective cognitive testing, and patient self-report tests. Patients were examined using single voxel proton magnetic resonance spectroscopy in the medial frontal cortex, posterior cingulate gyrus, and left thalamus at baseline and after the completion of chemotherapy on a 1.5 Tesla scanner. At the posttreatment evaluation as compared to baseline, 7 of the 10 (70%) patients reported worsening memory on the MD Anderson symptom inventory (annualized change = 1.82 ± 2.88, P = .08), while the delayed recall raw score of the Rey Osterrieth complex figure test did not change from pre- to post-chemotherapy (mean annualized change = 5.00 ± 14.38, P = .30). The annualized change in the creatine concentration in the posterior cingulate gyrus was statistically significant. The annualized change in the MD Anderson symptom inventory was negatively correlated with the annualized change in the medial frontal N-acetylaspartate (Spearman correlation coefficient [rho] = -0.78, P = .01) and positively correlated with the annualized change in the posterior cingulate gyrus creatine (rho = 0.66, P = .04). Annualized changes in the Rey Osterrieth complex figure test were positively correlated with annualized changes in choline (rho = 0.83, P = .01) in the medial frontal cortex, choline (rho = 0.76, P = .04) in the left thalamus, and creatine (rho = 0.73, P = .02) in the medial frontal cortex. Our data suggest that chemotherapy may lead to the worsening of self-reported memory function, which is associated with alterations in brain metabolites.

Efficacy of Treatment With Armodafinil for Cancer-Related Fatigue in Patients With High-grade Glioma: A Phase 3 Randomized Clinical Trial.

IMPORTANCE: Nearly 96% of patients with high-grade glioma (HGG) report moderate-to-severe fatigue. Armodafinil is a psychostimulant that might help cancer-related fatigue in patients with HGG. OBJECTIVE: To determine whether armodafinil reduces fatigue in patients with HGG and moderate-to-severe fatigue. DESIGN, SETTING, AND PARTICIPANTS: In this randomized multicenter, phase 3, double-blinded, placebo-controlled clinical trial, adults with HGG and moderate-to-severe fatigue who were clinically stable at least 4 weeks after completing radiation therapy were randomized to receive armodafinil daily (150 mg or 250 mg) or placebo over 8 weeks. A score of at least 6 out of 10 on severity scale for the brief fatigue inventory scale, with 10 being the worst, was required to suggest moderate-to-severe fatigue. Patients were allowed stable doses of corticosteroids but were excluded if they required increasing amounts of corticosteroids, were receiving some other treatment for fatigue, or had an uncontrolled seizure disorder. The study was conducted from June 2013 to December 15, 2019. INTERVENTIONS: Patients were randomized to 150 mg of armodafinil, 250 mg of armodafinil, or placebo for a total of 8 weeks with assessments at weeks 4 and 8. MAIN OUTCOMES AND MEASURES: The primary outcome was efficacy in treating cancer-related fatigue. Secondary outcomes included safety, neurocognitive function, and quality of life. Patients were evaluated at baseline and at weeks 4 and 8. Efficacy between the placebo and the 2 doses of study drug was determined by an improvement by 2 points on the 0 to 10 brief fatigue inventory scale. Kruskal-Wallis and χ2 tests were used and followed by confirmatory analyses. RESULTS: A total of 328 patients were enrolled, of whom 297 had evaluable end point data. Of these, 103 received 150 mg of armodafinil (mean [SD] age, 58.5 [11.9] years; 42 women [40.8%]), 97 250 mg of armodafinil (mean [SD] age, 56.6 [12.5] years; 37 women [38.1%]), and 97 placebo (mean [SD] age, 57.1 [12.5] years; 39 women [40.2%]). There was no difference in the proportion of patients who achieved clinically meaningful fatigue reduction between arms (28% [95% CI 20%-30%] for 150 mg of armodafinil, 28% [95% CI 19%-38%] for 250 mg of armodafinil, and 30% [95% CI 21%-40%] for placebo). There was a statistically significant reduction in global fatigue for corticosteroid users compared with nonusers (-0.7 [95% CI, -1.5 to -0.3] vs -1.7 [95% CI, -2.1 to -1.3]; P < .001). More patients (2 vs 7) reported insomnia with treatment with 250 mg of armodafinil. CONCLUSIONS AND RELEVANCE: The results of this randomized clinical trial found no meaningful benefit of using treatment with armodafinil to reduce cancer-related fatigue in patients with HGG. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01781468.

Pilot evaluation of a stellate ganglion block for the treatment of hot flashes.

PURPOSE: Hot flashes are a significant problem in breast cancer patients, especially because the most effective therapy, estrogen, is often contraindicated. Based on recent pilot data from a single group supporting the use of a stellate ganglion block for the treatment of hot flashes, the present pilot trial was done to further evaluate the hypothesis that a stellate ganglion block may be a safe and effective therapy for hot flashes. METHODS: In women with breast cancer who had hot flashes, a stellate ganglion block was performed after 1 week of baseline hot flash data collection. The main efficacy measures were the changes from baseline in hot flash frequency and hot flash score during the 6th week. RESULTS: Ten patients were enrolled between 4/23/2009 and 7/10/2009; eight patients were evaluable. After the stellate ganglion block, the mean hot flash frequency and score decreased from baseline values by over 60% during some of the post-treatment weeks. The mean hot flash frequency and score at week 6 decreased from baseline values by 44% and 45%, respectively. There were no significant adverse events clearly attributed to the stellate ganglion blocks. CONCLUSIONS: The results of this pilot trial support that stellate ganglion blocks may be a helpful therapy for hot flashes. A prospective placebo-controlled clinical trial should be done to more definitively determine this contention.

Community-based clinical oncology research trials for cancer-related fatigue.

Cancer-related fatigue (CRF) is a highly prevalent and debilitating symptom experienced by most cancer patients during, and often for considerable periods after, treatment. This symptom affects patients' overall quality of life and is characterized by persistent exhaustion and a decreased capacity to perform daily social and cognitive tasks. CRF is also one of the most commonly reported side effects of cancer and cancer treatments, including surgery, chemotherapy, radiotherapy, hormonal therapy, and biologic response modification therapy. Pharmacologic methods for treating CRF are not always reliable, and many patients continue to experience this symptom following pharmacologic interventions. Managing CRF is of importance to oncology researchers and clinical service providers. As of March 15, 2006, 76 National Institutes of Health sponsored studies examining CRF were actively recruiting subjects, and 15% of these studies were being conducted through the National Cancer Institute (NCI) Community Clinical Oncology Program (CCOP). This article will provide a description of-the NCI CCOP, its functions, and a brief overview of ongoing research on CRF both at our institution and other locations across the United States.

A Randomized Controlled Pilot Study Assessing Feasibility and Impact of Yoga Practice on Quality of Life, Mood, and Perceived Stress in Women With Newly Diagnosed Breast Cancer.

BACKGROUND: A breast cancer diagnosis can entail numerous physical and psychosocial challenges. Yoga practice (YP) may contribute to improved well-being for these patients. PRIMARY STUDY OBJECTIVE: Investigate feasibility and impact of YP on quality of life (QoL), mood, fatigue, and perceived stress immediately after breast cancer diagnosis. METHODS: Thirty women were randomly assigned to a yoga group (YG) or control group (CG) immediately after cancer diagnosis. SETTING: Pilot study conducted at an academic medical center breast clinic. PARTICIPANTS: Females (N = 30) who received a biopsy-proven breast cancer diagnosis without metastatic disease. INTERVENTION YG: One individual YP session at baseline, then 2 individual and 8 weekly group sessions followed by weekly gentle yoga at home (DVD). Questionnaires and saliva samples (ie, cortisol) completed at baseline and 12 weeks postdiagnosis. RESULTS: Both groups reported significant improvements in QoL postintervention but with no significant difference between groups. Emotional well-being, mood-related tension-anxiety, depression-dejection, and confusion-bewilderment scores improved for both groups, and cortisol and cortisone levels decreased. Lumpectomies were prevalent with YG (67%) and CG (47%). YP was rated as "very effective," providing relaxation (85%), stress relief (69%), and reduced muscle tension/general feeling of wellness (each 62%). CONCLUSION: Feasibility of YP immediately after breast cancer diagnosis was good. Improvement in emotional well-being, anxiety, depression, and levels of confusion was found in both groups. To our knowledge, this is the first study examining the impact of YP immediately after breast cancer diagnosis. Further research in this area is warranted.

An update on cancer- and chemotherapy-related cognitive dysfunction: current status.

The purpose of this review is to summarize the current literature on the effects of cancer treatment-related cognitive difficulties, with a focus on the effects of chemotherapy. Numerous patients have cognitive difficulties during and after cancer treatments and, for some, these effects last years after treatment. We do not yet fully understand which factors increase susceptibility to cognitive difficulties during treatment and which cause persistent problems. We review possible contributors, including genetic and biological factors. Mostly we focus is on cognitive effects of adjuvant chemotherapy for breast cancer; however, cognitive effects of chemotherapy on the elderly and brain tumor patients are also discussed.

The effect of modafinil on cognitive function in breast cancer survivors.

BACKGROUND: The authors conducted a randomized clinical trial examining the effects of modafinil in reducing persistent fatigue in patients after treatment for cancer and performed secondary analyses to assess the effect of modafinil on cognitive function. METHODS: Breast cancer patients who reported a score of >or=2 on the Brief Fatigue Inventory were enrolled in the study. In phase 1 (P1), patients received 200 mg modafinil open-label once daily for 4 weeks. In phase 2 (P2), patients with a positive response after P1 were randomized either to an additional 4 weeks of modafinil or to placebo. Tests of memory and attention selected from the Cognitive Drug Research (CDR) computerized cognitive assessment were performed at baseline (before modafinil) and after completing phases 1 and 2. The paired differences for each test score were subjected to a Wilcoxon signed rank test. RESULTS: Of the 82 women who were enrolled, 76 completed P1, and 68 completed all assessments in the study. Modafinil had a significant effect on the Speed of Memory (P = .0073) and Quality of Episodic Memory (P < .0001) during P1 of the study. After randomization at Week 8, those patients who continued modafinil demonstrated significantly greater improvement in Speed of Memory (P = .029), Quality of Episodic Memory (P = .0151), and mean Continuity of Attention (P = .0101) relative to the group that was switched to placebo. CONCLUSIONS: The authors found that modafinil improved cognitive performance in breast cancer survivors by enhancing some memory and attention skills. Although confirmation is needed, these findings suggest that modafinil may enhance quality of life in this patient population.

Assessment of cancer-related fatigue: implications for clinical diagnosis and treatment.

Cancer-related fatigue (CRF) is a highly prevalent and debilitating symptom experienced by most cancer patients during, and often for considerable periods after, treatment. The recognition of the importance of CRF to patients' psychosocial and cognitive functioning, as well as to their quality of life, has driven the development of a wide range of assessment tools for screening and diagnosis of CRF. Over 20 different measures have been used to assess CRF from either a unidimensional or multi-dimensional perspective. Unidimensional measures are often single-question scales that generally focus on identifying the occurrence and severity of CRF, whereas multidimensional measures may also examine the effect of CRF across several domains of physical, socio-emotional, and cognitive functioning. This paper provides an overview and critique of measures commonly used to assess CRF. Single-question assessment is the most commonly used and the most useful methodology. Strategies to facilitate reliable assessment of CRF are also discussed. Disclosure of potential conflicts of interest is found at the end of this article.

Pharmacologic treatment of cancer-related fatigue.

Fatigue is the most commonly reported symptom in patients with cancer, with a prevalence of over 60% reported in the majority of studies. This paper systematically reviews pharmacologic agents in the treatment of cancer-related fatigue (CRF). We conducted a literature review of clinical trials that assessed pharmacologic agents for the treatment of CRF. These agents include hematopoietics (for anemia), corticosteroids, and psychostimulants. Other therapeutic agents that are less well studied for CRF but are currently the focus of clinical trials include l-carnitine, modafinil, bupropion, and selective serotonin reuptake inhibitors such as paroxetine. Disclosure of potential conflicts of interest is found at the end of this article.

Self-reported cognitive impairment in patients with cancer.

PURPOSE: Cancer patients often report cognitive impairment, manifested as problems with concentration and memory, following cancer therapy. As part of a large multicenter survey of cancer patients undergoing treatment, we investigated the frequency and severity of self-reported problems with memory and concentration over time. METHODS: A total of 595 patients undergoing treatment for solid tumors self-rated problems with memory and concentration, using an 11-point Likert scale (0 = "not present" to 10 = "as bad as you can imagine") at baseline before treatment began (T1), at their worst during treatment (T2), and at 6 months following treatment (T3). Any symptom level ≥ 7 was classified as "severe." Paired or independent t tests (as appropriate) with a Bonferroni correction were used to examine differences in symptoms over time and between patients treated with chemotherapy, radiation therapy, or both. RESULTS: Concentration problems were reported by 48% of the 595 participants at T1 (5% severe), 67% at T2 (18% severe), and 58% (8% severe) at T3. Problems with memory were reported by 53% at T1 (4% severe), 67% (18% severe) at T2, and 68% (11% severe) at T3. The average frequency and severity of both symptoms in patients receiving chemotherapy, with or without radiation, increased significantly between T1 and T2 (P < .001). Both symptoms were less severe in patients receiving radiation alone at all three measurements than in either of the chemotherapy groups (all P values < .001). Symptoms at T3 were significantly higher than T1 for all groups (P < .001). CONCLUSION: A significant proportion of patients undergoing cancer therapy self-report problems with memory and concentration. Cognitive problems get worse during treatment and are still in evidence 6 months following the conclusion of treatments.

Cancer-related fatigue and sleep disorders.

Sleep disorders, such as difficulty falling asleep, problems maintaining sleep, poor sleep efficiency, early awakening, and excessive daytime sleepiness, are prevalent in patients with cancer. Such problems can become chronic in some patients, persisting for many months or years after completion of cancer therapy. For patients with cancer, sleep is potentially affected by a variety of factors, including the biochemical changes associated with the process of neoplastic growth and anticancer treatments, and symptoms that frequently accompany cancer, such as pain, fatigue, and depression. Fatigue is highly prevalent and persistent in patients with cancer and cancer survivors. Although cancer-related fatigue and cancer-related sleep disorders are distinct, a strong interrelationship exists between these symptoms, and a strong possibility exists that they may be reciprocally related. The majority of studies that have assessed both sleep and fatigue in patients with cancer provide evidence supporting a strong correlation between cancer-related fatigue and various sleep parameters, including poor sleep quality, disrupted initiation and maintenance of sleep, nighttime awakening, restless sleep, and excessive daytime sleepiness. This paper reviews the data from these studies with a view toward suggesting further research that could advance our scientific understanding both of potential interrelationships between sleep disturbance and cancer-related fatigue and of clinical interventions to help with both fatigue and sleep disturbance. Disclosure of potential conflicts of interest is found at the end of this article.

Behavioral interventions in treating anticipatory nausea and vomiting.

Anticipatory nausea and vomiting (ANV) is associated with a significant reduction in the quality of life for many chemotherapy patients. The use of 5-hydroxytryptamine type 3 receptor antagonists provides some relief for chemotherapy-induced nausea and vomiting, but does not seem to control ANV. Nonpharmacologic approaches, which include behavioral interventions, may provide the greatest promise in relieving symptoms. Little evidence supports the use of complementary and alternative methods, such as acupuncture and acupressure, in relieving ANV. Behavioral interventions, especially progressive muscle relaxation training and systematic desensitization, should be considered important methods for preventing and treating ANV.