Potential drug interactions and chemotoxicity in older patients with cancer receiving chemotherapy.

PURPOSE: Increased risk of drug interactions due to polypharmacy and aging-related changes in physiology among older patients with cancer is further augmented during chemotherapy. No previous studies examined potential drug interactions (PDIs) from polypharmacy and their association with chemotherapy tolerance in older patients with cancer. METHODS: This study is a retrospective medical chart review of 244 patients aged 70+ years who received chemotherapy for solid or hematological malignancies. PDI among all drugs, supplements, and herbals taken with the first chemotherapy cycle were screened for using the Drug Interaction Facts software, which classifies PDIs into five levels of clinical significance with level 1 being the highest. Descriptive and correlative statistics were used to describe rates of PDI. The association between PDI and severe chemotoxicity was tested with logistic regressions adjusted for baseline covariates. RESULTS: A total of 769 PDIs were identified in 75.4% patients. Of the 82 level 1 PDIs identified among these, 32 PDIs involved chemotherapeutics. A large proportion of the identified PDIs were of minor clinical significance. The risk of severe non-hematological toxicity almost doubled with each level 1 PDI (OR=1.94, 95% CI: 1.22-3.09), and tripled with each level 1 PDI involving chemotherapeutics (OR=3.08, 95% CI: 1.33-7.12). No association between PDI and hematological toxicity was found. CONCLUSIONS: In this convenience sample of older patients with cancer receiving chemotherapy we found notable rates of PDI and a substantial adjusted impact of PDI on risk of non-hematological toxicity. These findings warrant further research to optimize chemotherapy outcomes.

Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy.

PURPOSE: Evidence is mixed regarding long-term cognitive deficits in patients treated with chemotherapy. Previous meta-analyses have not focused specifically on the postchemotherapy period and have not incorporated several recent studies. The goal of the current study was to conduct a meta-analysis of cognitive functioning in breast cancer survivors who were treated with chemotherapy ≥ 6 months previously. METHODS: A search of PubMed, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library yielded 2,751 abstracts, which were independently evaluated by pairs of raters. Meta-analysis was conducted on 17 studies of 807 patients previously treated with standard-dose chemotherapy for breast cancer. Neuropsychological tests were categorized according to eight cognitive domains: attention, executive functioning, information processing, motor speed, verbal ability, verbal memory, visual memory, and visuospatial ability. RESULTS: Deficits in cognitive functioning were observed in patients treated with chemotherapy relative to controls or prechemotherapy baseline in the domains of verbal ability (g = -0.19; P < .01) and visuospatial ability (g = -0.27; P < .01). Patients treated with chemotherapy performed worse than noncancer controls in verbal ability and worse than patients treated without chemotherapy in visuospatial ability (both P < .01). Age, education, time since treatment, and endocrine therapy did not moderate observed cognitive deficits in verbal ability or visuospatial ability (all P ≥ .51). CONCLUSION: Results indicate that, on average, observed cognitive deficits in patients with breast cancer previously treated with chemotherapy are small in magnitude and limited to the domains of verbal ability and visuospatial ability. This information can be used to inform interventions to educate patients with breast cancer regarding the long-term impact of chemotherapy on cognitive functioning.

Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma.

PURPOSE: Vaccination with hybridoma-derived autologous tumor immunoglobulin (Ig) idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) and administered with granulocyte-monocyte colony-stimulating factor (GM-CSF) induces follicular lymphoma (FL) -specific immune responses. To determine the clinical benefit of this vaccine, we conducted a double-blind multicenter controlled phase III trial. PATIENTS AND METHODS: Treatment-naive patients with advanced stage FL achieving complete response (CR) or CR unconfirmed (CRu) after chemotherapy were randomly assigned two to one to receive either Id vaccine (Id-KLH + GM-CSF) or control (KLH + GM-CSF). Primary efficacy end points were disease-free survival (DFS) for all randomly assigned patients and DFS for randomly assigned patients receiving at least one dose of Id vaccine or control. RESULTS: Of 234 patients enrolled, 177 (81%) achieved CR/CRu after chemotherapy and were randomly assigned. For 177 randomly assigned patients, including 60 patients not vaccinated because of relapse (n = 55) or other reasons (n = 5), median DFS between Id-vaccine and control arms was 23.0 versus 20.6 months, respectively (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.16; P = .256). For 117 patients who received Id vaccine (n = 76) or control (n = 41), median DFS after randomization was 44.2 months for Id-vaccine arm versus 30.6 months for control arm (HR, 0.62; 95% CI, 0.39 to 0.99; P = .047) at median follow-up of 56.6 months (range, 12.6 to 89.3 months). In an unplanned subgroup analysis, median DFS was significantly prolonged for patients receiving IgM-Id (52.9 v 28.7 months; P = .001) but not IgG-Id vaccine (35.1 v 32.4 months; P = .807) compared with isotype-matched control-treated patients. CONCLUSION: Vaccination with patient-specific hybridoma-derived Id vaccine after chemotherapy-induced CR/CRu may prolong DFS in patients with FL. Vaccine isotype may affect clinical outcome and explain differing results between this and other controlled Id-vaccine trials.

Is the effect of reported physical activity on disability mediated by cognitive performance in white and african american older adults?

This study examined if reported physical activity has beneficial outcomes on disability through cognitive performance-mediated effects and if these mediation effects are comparable for White and African American elders. Longitudinal data from the Assets and Health Dynamics among the Oldest Old study (N = 4,472) are used to test mediation in multilevel models. During the 7-year follow-up, cognitive performance mediated the effects of reported physical activity on disability in the entire sample and in Whites but not in African Americans. Our results indicate that reported physical activity may delay the disability development through improvement in cognitive performance. Unmeasured education and comorbidity influences may have obscured the mediation effects in African Americans. Reported physical activity plays a key role in the independence of older adults and should be particularly promoted in African Americans and during the entire life course.

Perceptions of Illness, coping, and well-being in persons with mild cognitive impairment and their care partners.

Despite greater attention to mild cognitive impairment (MCI), little is known about reactions to this potentially threatening diagnosis among persons with MCI (PWMCI) and their care partners. Psychologic reactions, perceptions of illness, and coping responses of 46 individuals recently diagnosed with MCI and 29 care partners were assessed with questionnaires assessing psychologic well-being, illness perceptions, coping, and perceived needs for services. Care partners and PWMCI report normal levels of psychologic well-being, showing less distress than is commonly found in Alzheimer disease (AD) caregivers. Problem-focused (eg, active coping) and emotion-focused coping strategies (eg, acceptance) were used more often than dysfunctional coping strategies (eg, self-distraction) by PWMCI and care partners. Both groups tended to minimize the likelihood of conversion to AD, and endorsed mental and physical exercise, optimism, dietary changes, and stress reduction as strategies to prevent conversion. Although PWMCI minimized their impairment, care partners reported providing an average of 24 hours per week of caregiving and reported that the PWMCI did need significant help with complex activities. Respondents reported using few formal services but they anticipate substantial future need for services. Results suggest that PWMCI and care partners are likely to minimize the threat of AD and to perceive that conversion is controllable and preventable with health promotion activities. Study implications for the development of intervention programs for PWMCI and their care partners are discussed.

The white-black disability gap revisited: does an incident heart attack change this gap?

BACKGROUND: A myocardial infarction (MI) results typically in abrupt functional deterioration immediately postevent, followed by recovery. The post-MI health disparities experienced by black older adults may be attributable to the social and health correlates of race. We explored patterns of change in functional status in a community-based sample of 243 older white and black persons hospitalized for an incident MI. METHODS: The study sample was drawn from the Established Populations for Epidemiologic Studies of the Elderly (EPESE). All older adults hospitalized for an incident MI between the first two waves of data collection were followed up yearly for two additional years. Nonlinear quadratic trajectories of functional status, as measured by disability in activities of daily living (ADL) and functional limitation (FL), were fit using mixed-effects models. RESULTS: Although there were no nonlinear differences in ADL trajectories, there was a faster nonlinear rate of change in FL in older blacks compared to whites, independent of other social and health factors. The baseline white-black gap in FL widened after the MI by the first follow-up, continued to widen at a less accelerated pace until the second follow-up, and narrowed by the third follow-up. CONCLUSIONS: Disparities in relevant social and health factors did not account for the more abrupt deterioration in FL postevent or for the more substantial recovery in older blacks compared to older whites. Disparities in therapeutic strategies and the "survival of the fittest" may underlie the pattern of this white-black gap in FL after an incident MI.

Stages of change for osteoporosis preventive behaviors: a construct validation study.

OBJECTIVE: This article presents a construct validation study for osteoporosis preventive behaviors based on a survey completed by 113 older adults. METHODS: Participants were classified using stages of change for osteoporosis preventive behaviors according to an algorithm adapted from the Transtheoretical Model of health behavior change. RESULTS: One-way analyses of variance and a hierarchical regression model indicate that stage of change location is significantly related to one's level of knowledge about osteoporosis as well as age, gender, and educational attainment. These findings bring support to the validity of the instrument. DISCUSSION: Findings from this study indicate that elders' attitudes and knowledge about osteoporosis reflect public health messages heralding osteoporosis as the disease of the older White women. Significant health care expenditures in the nontargeted groups call for a revision in these messages. Further applications with more heterogeneous samples are necessary for thorough validation and reliability testing of the proposed instrument.