We conducted a double-blind randomized clinical trial of the following four regimens for controlling delayed nausea (DN): group 1: palonosetron + dexamethasone on day 1 with prochlorperazine on days 2 and 3; group 2: granisetron + dexamethasone on day 1 with prochlorperazine on days 2 and 3; group 3: aprepitant + palonosetron + dexamethasone on day 1 with aprepitant + dexamethasone on days 2 and 3; and group 4: palonosetron + dexamethasone on day 1 with prochlorperazine + dexamethasone on days 2 and 3.
Patients and Methods
Chemotherapy-naive patients received doxorubicin, epirubicin, cisplatin, carboplatin, or oxaliplatin. The primary end point was average nausea assessed four times daily on days 2 and 3. Primary analyses were whether nausea control would be improved by using palonosetron versus granisetron on day 1 (group 1 v group 2); by adding dexamethasone on days 2 and 3 (group 1 v group 4); and by using aprepitant versus prochlorperazine (group 3 v group 4). Statistical significance was set at P = .017.
Two hundred thirty-four, 234, 241, and 235 evaluable patients were accrued to groups 1, 2, 3, and 4, respectively. Adjusted mean differences for the three planned analyses were as follows: palonosetron versus granisetron: −0.01 (95% CI, −0.23 to 0.20; P = .72); adding dexamethasone on days 2 and 3: 0.20 (95% CI, −0.02 to 0.41; P = .01); and using aprepitant versus prochlorperazine: −0.03 (95% CI, −0.24 to 0.19; P = .56).
The addition of dexamethasone on days 2 and 3 reduced DN. Palonosetron and granisetron have similar effects on DN. The beneficial effect of adding aprepitant for control of DN was the same as adding prochlorperazine.
To identify whether a history of cancer is associated with specific geriatric syndromes in older patients.
Patients and Methods
Using the 2003 Medicare Current Beneficiary Survey, we analyzed a national sample of 12,480 community-based elders. Differences in prevalence of geriatric syndromes between those with and without cancer were estimated. Multivariable logistic regressions were used to evaluate whether cancer was independently associated with geriatric syndromes.
Two thousand three hundred forty-nine (18%) reported a history of cancer. Among those with cancer, 60.3% reported one or more geriatric syndromes as compared with 53.2% of those without cancer (P < .001). Those with cancer overall had a statistically significantly higher prevalence of hearing trouble, urinary incontinence, falls, depression, and osteoporosis than those without cancer. Adjusting for possible confounders, those with a history of cancer were more likely to experience depression (adjusted odds ratio [OR], 1.15; 95% CI, 1.02 to 1.30; P = .023), falls (adjusted OR, 1.17; 95% CI, 1.04 to 1.32; P = .010), osteoporosis (adjusted OR, 1.21; 95% CI, 1.06 to 1.38; P = .004), hearing trouble (adjusted OR, 1.28; 95% CI, 1.08 to 1.52; P = .005), and urinary incontinence (adjusted OR, 1.42; 95% CI, 1.20 to 1.69; P < .001). Analysis of specific cancer subtypes showed that lung cancer was associated with vision, hearing, and eating trouble; prostate cancer was associated with incontinence and falls; cervical/uterine cancer was associated with falls and osteoporosis; and colon cancer was associated with depression and osteoporosis.
Elderly patients with cancer experience a higher prevalence of geriatric syndromes than those without cancer. Prospective studies that establish the causal relationships between cancer and geriatric syndromes are necessary.
Prostate-specific antigen (PSA) testing for prostate cancer (PCa) is controversial, with concerning rates of both over- and under-screening. The reasons for the observed rates of screening are unknown, and few studies have examined the relationship of psychological health to PSA screening rates. Understanding this relationship can help guide interventions to improve informed-decision making (IDM) for screening.
A nationally-representative sample of men 57–85 years old without PCa (N=1,169) from the National Social life, Health and Aging Project (NSHAP) was analyzed. The independent relationship of validated psychological health scales measuring stress, anxiety, and depression to PSA testing rates was assessed using multvariable logistic regression analyses.
PSA screening rates were significantly lower for men with higher perceived stress (OR=0.76, p=0.006), but not for higher depressive symptoms (OR=0.89, p=0.22) when accounting for stress. Anxiety influences PSA screening through an interaction with number of doctor visits (p=0.02). Among the men who visited the doctor 1 time, those with higher anxiety were less likely to be screened (OR=0.65, p=0.04). Conversely, among those who visited the doctor 10+ times with higher anxiety were more likely to be screened (OR=1.71, p=0.04).
Perceived stress significantly lowers PSA screening likelihood, and it appears to partly mediate the negative relationship of depression with screening likelihood. Anxiety affects PSA screening rates differently for men with different numbers of doctor visits. Interventions to influence PSA screening rates should recognize the role of the patients’ psychological state to improve their likelihood of making informed decisions and improve screening appropriateness.
prostate cancer; screening; stress; anxiety; depression
Little is known about complementary medication use among older adults with cancer, particularly those undergoing chemotherapy. The purpose of this study was to evaluate the prevalence of complementary medication use and to identify factors associated with its use among older adults with cancer.
The prevalence of complementary medication use (defined as herbal agents, minerals, or other dietary supplements excluding vitamins) was evaluated in a cohort of adults aged ≥65 years who were about to start chemotherapy for their cancer. The association between complementary medication use and patient characteristics (sociodemographics; comorbidity; functional, nutritional, psychological, and cognitive status); medication use (number of medications and concurrent vitamin use); and cancer characteristics (type and stage) was analyzed.
The cohort included 545 patients [mean age 73 years (range 65–91); 52% female] with cancer (61% Stage IV). Seventeen percent (N=93) of these patients reported using ≥1 complementary medications [mean number of complementary medications among users was 2 (range 1–10)]. Complementary medication use was associated with: 1) earlier cancer stage, with 29% of those with stages I–II vs. 17% with III–IV (OR=2.05, 95% CI:1.21–3.49); and 2) less impairment with instrumental activities of daily living (OR=1.39, 95% CI:1.12–1.73).
Complementary medication use was reported by 17% of older adults with cancer and was more common among those with less advanced disease (receiving adjuvant potentially curative treatment) and higher functional status. Further studies are needed to determine the association between complementary medication use and cancer outcomes among older adults.
Herbals; Complementary Medicine; Older Adults; Cancer; Chemotherapy
Guidelines recommend informed decision-making regarding prostate specific antigen (PSA) screening for men with at least 10 years of remaining life expectancy (RLE). Comorbidity measures have been used to judge RLE in previous studies, but assessments based on other common RLE measures are unknown. We assessed whether screening rates varied based on four clinically relevant RLE measures, including comorbidities, in a nationally-representative, community-based sample.
Using the National Social Life, Health and Aging Project (NSHAP), we selected men over 65 without prostate cancer (n=709). They were stratified into three RLE categories (0–7 years, 8–12 years, and 13+ years) based on validated measures of comorbidities, self-rated health status, functional status, and physical performance. The independent relationship of each RLE measure and a combined measure to screening was determined using multivariable logistic regressions.
Self-rated health (OR = 6.82; p < 0.01) most closely correlated with RLE-based screening, while the comorbidity index correlated the least (OR = 1.50; p = 0.09). The relationship of RLE to PSA screening significantly strengthened when controlling for the number of doctor visits, particularly for comorbidities (OR= 43.6; p < 0.001). Men who had consistent estimates of less than 7 years RLE by all four measures had an adjusted PSA screening rate of 43.3%.
Regardless of the RLE measure used, men who were estimated to have limited RLE had significant PSA screening rates. However, different RLE measures have different correlations with PSA screening. Specific estimates of over-screening should therefore carefully consider the RLE measure used.
prostate cancer; older adults; screening; PSA; remaining life expectancy; comorbidity
In September 2010, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging, conducted the first of three planned conferences to discuss research methodology to generate the highest quality research in older adults with cancer and then disseminate these findings among those working in the fields of cancer and aging. Conference speakers discussed the current level of research evidence in geriatric oncology, outlined the current knowledge gaps, and put forth principles for research designs and strategies that would address these gaps within the next 10 years. It was agreed that future oncology research trials that enroll older adults should include: 1) improved standardized geriatric assessment of older oncology patients, 2) substantially enhanced biological assessment of older oncology patients, 3) specific trials for the most vulnerable and/or those older than 75 years, and 4) research infrastructure that specifically targets older adults and substantially strengthened geriatrics and oncology research collaborations. This initial conference laid the foundation for the next two meetings, which will address the research designs and collaborations needed to enhance therapeutic and intervention trials in older adults with cancer.
While the benefits of exercise for managing cancer-and treatment-related side effects has been shown among various populations of cancer survivors, a relative dearth of information exists among older cancer patients.
To determine the prevalence of exercise participation during and after primary cancer treatment in older (≥65 years) and the oldest (≥80 years) cancer patients and to examine the relationships between exercise, symptoms, and self-rated health (SRH).
Materials and Methods
408 newly diagnosed older cancer patients (mean age=73, range=65-92) scheduled to receive chemotherapy and/or radiation therapy reported symptoms and SRH prior to, during, and 6 months after treatment, and exercise participation during and following treatment.
Forty-six percent of older and 41% of the oldest patients reported exercising during treatment. Sixty percent of older and 68% of the oldest patients reported exercising in the 6 months thereafter. Older patients who exercised during treatment reported less shortness of breath and better SRH during treatment, and better SRH following treatment. The oldest patients who exercised during treatment reported less memory loss and better SRH during treatment and less fatigue and better SRH following treatment. The oldest patients who exercised following treatment reported less fatigue, skin problems, and total symptom burden following treatment.
These data suggest a willingness of older cancer patients to attempt exercise during and after treatment. Exercise during these times is associated with less severe symptoms; further clinical research examining the efficacy of formal exercise interventions to reduce symptoms and improve SRH in older cancer patients is needed.
elderly; exercise; physical activity; neoplasms; side effects; symptoms; chemotherapy; radiation therapy
To evaluate the relationship of age with symptoms and interference with daily function and QOL during RT.
A prospective observational study.
A university-based radiation oncology department.
903 cancer patients who received radiation therapy (RT). The mean age was 61 yrs (18-92) and 41% were ≥ 65 yrs.
A symptom inventory was administered pre- and post-RT. Patients rated 10 symptoms and their interference with daily function and QOL on a Likert scale from 0 (not present) to 10 (as bad as possible). A total symptom score was calculated by adding the ratings of individual symptoms. T-tests, Pearson correlation coefficients, and mixed modeling were used to investigate relationships between symptoms and their interference with daily function and QOL.
For older and younger patients, the total symptom score worsened during RT (p's < .001). There were no differences in the change in total symptom burden and interference with QOL between older and younger patients during RT. After RT, although younger patients reported significantly worse pain (p = .03), nausea (p <.01), and sleep disturbance (p <.01), symptom interference with walking was more severe in older patients (p = .01). Mixed modeling showed that older age (p=<.001), time of survey (after RT, p<.001), and age*time interaction (p<.001) increased the likelihood of reporting that symptoms interfered with walking.
The prevalence of symptoms was similar for older and younger patients during RT. Older patients are more likely to report that symptoms interfere with walking after RT.
elderly; cancer; symptoms; radiotherapy
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 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.
Early androgen deprivation therapy (ADT) has no proven survival advantage in older men with biochemical recurrence (BCR) of prostate cancer (PCa), and it may contribute to geriatric frailty; we tested this hypothesis.
We conducted a case-control study of men aged 60+ with BCR on ADT (n=63) versus PCa survivors without recurrence (n=71). Frailty prevalence, “obese” frailty, Short Physical Performance Battery (SPPB) scores and falls were compared. An exploratory analysis of frailty biomarkers (CRP, ESR, hemoglobin, albumin, and total cholesterol) was performed. Summary statistics, univariate and multivariate regression analyses were conducted.
More patients on ADT were obese (BMI >30; 46.2% vs. 20.6%; p=0.03). There were no statistical differences in SPPB (p=0.41) or frailty (p=0.20). Using a proposed “obese” frailty criteria, 8.7% in ADT group were frail and 56.5% were “prefrail”, compared with 2.9% and 48.8% of controls (p=0.02). Falls in the last year were higher in ADT group (14.3% vs. 2.8%; p=0.02). In analyses controlling for age, clinical characteristics, and comorbidities, the ADT group trended toward significance for “obese” frailty (p = 0.14) and falls (OR = 4.74, p = 0.11). Comorbidity significantly increased the likelihood of “obese” frailty (p=0.01) and falls (OR 2.02, p = 0.01).
Men with BCR on ADT are frailer using proposed modified “obese” frailty criteria. They may have lower performance status and more falls. A larger, prospective trial is necessary to establish a causal link between ADT use and progression of frailty and disability.
prostate cancer; biochemical recurrence; androgen deprivation therapy; frailty; older adults
In many neurodegenerative diseases abnormal concentrations of cytokines and chemokines affect neuronal integrity leading to cognitive impairments; altered levels of these molecules could also play a role in cancer- and cancer-treatment related cognitive difficulties. Patients receiving doxorubicin-based (with cyclophosphamide, or cyclophosphamide plus fluorouracil; AC/CAF) chemotherapy or cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy report experiencing cognitive difficulties; because these regimens work by different modes of action, it is possible that they differentially affect cytokine levels.
This secondary study examined the relationships between cytokine levels (i.e., IL-6, IL-8, and MCP-1) and type of chemotherapy among 54 early-stage breast cancer patients receiving AC/CAF or CMF. Cytokine levels were assessed at two time-points: prior to on-study chemotherapy cycle 2 (Cycle 2) and after 2 consecutive chemotherapy cycles (prior to on-study cycle 4; Cycle 4).
Analyses of variance using Cycle 2 levels as a covariate (ANCOVA) were used to determine differences between chemotherapy groups. Levels of IL-6, IL-8, and MCP-1 increased in the AC/CAF group and decreased in the CMF group; the only significant between-group change was in IL-6 (p<0.05).
These preliminary results suggest that AC/CAF chemotherapy is more cytokine inducing than CMF; future studies should explore the distinct inflammatory responses elicited by different chemotherapy regimens.
chemotherapy; cytokines; cancer; cognitive impairment; immune response
Cancer-related fatigue is the most common side effect reported by cancer patients during and after treatment. Cancer-related fatigue significantly interferes with a patient’s ability to perform activities of daily living and maintain functional independence and quality of life. Cancer-related fatigue can also interfere with a patient’s ability to complete treatments. The purpose of this article is to provide an overview of cancer-related fatigue, its pathopsychophysiology, and the role of exercise in the management of this side effect.
Cancer; fatigue; exercise; symptoms
Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity.
Patients and Methods
Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events.
In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P < .001).
A risk stratification schema can establish the risk of chemotherapy toxicity in older adults. Geriatric assessment variables independently predicted the risk of toxicity.
Prostate cancer is the most common malignancy in older men. With the aging of the population, the number of older men with prostate cancer will grow rapidly. Androgen deprivation therapy (ADT) is the mainstay of treatment for men with systemic disease and is increasingly utilized as primary therapy or in combination with other therapies for localized disease. Side effects of therapy are multifold and include hot flashes, osteoporosis, and adverse psychological and metabolic effects. Recent research has illustrated that ADT can negatively impact the functional, cognitive, and physical performance of older men. Patients with prostate cancer, despite recurrence of the disease, have a long life expectancy and may be subjected to the side effects of ADT for many years. This review highlights the complications of ADT and approaches to management. We also provide recommendations for assessment and management of ADT complications among the most vulnerable and frail older male patients.
Disability; Geriatric assessment; Prostate cancer; Vulnerable elders; Functional impairment; Androgen deprivation; Quality of life; Complications
Men experience a decrease in lean muscle mass and strength during the first year of androgen deprivation therapy (ADT). The prevalence of falls and physical and functional impairment in this population have not been well described.
A total of 50 men aged 70 years and older (median 78) receiving ADT for systemic prostate cancer (80% biochemical recurrence) underwent functional and physical assessments. The functional assessments included Katz’s Activities of Daily Living (ADLs) and Lawton’s Instrumental Activities of Daily Living (IADLs). Patients completed the Vulnerable Elder’s Survey-13, a short screening tool of self-perceived functional and physical performance ability. Physical performance was assessed using the Short Physical Performance Battery. The history of falls was recorded. Of the 50 patients, 40 underwent follow-up assessment with the same instruments 3 months after the initial assessment.
Of the 50 men, 24% had impairment in the ADLs, 42% had impairment in the IADLs, 56% had abnormal Short Physical Performance Battery findings, and 22% reported falls within the previous 3 months. Within the Short Physical Performance Battery, deficits occurred within all subcomponents (balance, walking, and chair stands). On univariate analysis, age, deficits in ADLs and IADLs, and abnormal cognitive and functional screen findings were associated with an increased risk of abnormal physical performance. ADL deficits, the use of an assistive device, and abnormal functional screen findings were associated with an increased risk of falling.
The results of our study have shown that older men with prostate cancer receiving long-term ADT exhibit significant functional and physical impairment and are at risk of falls that is greater than that for similar-aged cohorts. Careful assessment of the functional and physical deficits in older patients receiving ADT is warranted.
The type and quantity of information needed varies between patients who actively seek information and those who tend to avoid information. We analyzed data from a longitudinal study of adult cancer patients from outpatient clinics for whom information needs and behaviors were assessed by survey before and after treatment. We evaluated the relationships between information-seeking style (active, moderately active and passive styles) and demographics, cancer type, and health status for the pretreatment and posttreatment periods and overall. The Generalized Estimating Equations (GEE) approach was used to model the log odds of more active to more passive information-seeking preferences taking into consideration both the pretreatment and posttreatment periods.
Analyses included 731 case participants, including female breast cancer patients (51%), male genitourinary cancer patients (18%), and lung cancer patients of both sexes (10%). At pretreatment, 17% reported an active information-seeking style, 69% were moderately active, and 14% were passive. During this period, 19% of those with at least some college education reported being very active compared to 14% of those with less education. With adjustment for all other covariates, male genitourinary and lung cancer patients had a higher odds of having a more active information-seeking style in the pretreatment than in the posttreatment period, with an odds of 4.5 (95% confidence interval [CI]: 2.4–8.4) and 5.4 (95% CI: 2.7–10.6), respectively. Controlling for all covariates, breast cancer patients had 1.5 (95% CI: 1.0–2.1) times higher odds of being more active in seeking information than other patients.
Public health researchers and clinicians must work together to develop the most effective strategy for meeting the informational needs of these patients before and after treatment.
Physical activity may play an important role in the rehabilitation of cancer survivors during and following treatment. Current research suggests numerous beneficial outcomes are experienced in cancer survivors undergoing exercise interventions during or following cancer treatment. Exercise not only plays a role in managing side effects but also improves functional capacity and quality of life. The purpose of this article is to provide an overview of the oncology literature supporting the use of exercise as an effective intervention for improving cancer-related fatigue, other side effects, functional capacity, and quality of life among cancer survivors.
Breast cancer survivors experience diminished health-related quality of life (HRQOL). We report on the influence of tai chi chuan exercise (TCC) on HRQOL and explore associations between changes in HRQOL and biomarkers.
Breast cancer survivors (N=21) were randomly assigned to TCC or standard support therapy (SST) for 12 weeks (three times/week; 60 min/session). Interleukin-6, interleukin-8 (IL-8), insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein (IBFBP)-1, IGFBP-3, glucose, insulin, and cortisol were measured pre- and postintervention. Overall HRQOL and subdomains were assessed at preintervention (T1), midintervention (T2) and postintervention (T3) and biomarkers at T1 and T3.
The TCC group improved in total HRQOL (T1–T2: CS=8.54, P=0.045), physical functioning (T1–T2:CS=1.89, P=0.030), physical role limitations (T1–T2 CS=1.55, P=0.023), social functioning (T1–T3:CS=1.50, P=0.020), and general mental health (T1–-T2:CS=2.67, P=0.014; T1–T3: CS=2.44, P=0.019). The SST improved in social functioning (T1–T2:CS=0.64, P=0.043) and vitality (T1–T2:CS=0.90, P=0.01). There were relationships between changes in IGF-1 and overall HRQOL (r=−0.56; P<0.05), physical role limitation (r=−0.68; P<0.05), and social functioning (r=−0.56; P<0.05). IGFBP-1 changes were associated with physical role limitation changes (r=0.60; P<0.05). IGFBP-3 changes were associated with physical functioning changes (r=0.46; P≤0.05). Cortisol changes were associated with changes in physical role limitations (r=0.74; P<0.05) and health perceptions (r=0.46; P<0.05). Glucose changes were associated with emotional role limitation changes (r=−0.70; P<0.001). IL-8 changes were associated with emotional role limitation changes (r=0.59; P<0.05).
TCC may improve HRQOL by regulating inflammatory responses and other biomarkers associated with side effects from cancer and its treatments. Implications for cancer survivors TCC may be an intervention capable of improving HRQOL in breast cancer survivors.
Breast cancer; Inflammation; Exercise; Quality of life
Studies published prior to 1980 failed to find an association between smoking and colorectal cancer, while subsequent studies reported an association after accounting for a three to four decade initiation period. The aims of this study were to determine the effect of accounting for secondhand smoke (SHS) exposure on the association between smoking and colorectal cancer and to determine the association between SHS and colorectal cancer.
Approximately 1,200 colorectal cancer cases treated at Roswell Park Cancer Institute between 1982 and 1998 were matched to 2,400 malignancy-free controls. The effect of accounting for SHS exposure was determined by comparing the odds ratios (OR) for each smoking variable in the overall sample and then for those who reported no current SHS exposure.
A small, significant increase in colorectal cancer odds was noted for heavy, long-term smoking males when not accounting for SHS exposure (>45 PY: OR = 1.34; 95% CI 1.04–1.72). OR increased when the analyses were restricted to individuals reporting no current SHS exposure (>45 PY: OR = 2.40; 95% CI 1.36–4.23).
Accounting for SHS exposure resulted in a substantial increase in the odds of colorectal cancer for all smoking variables in this study. Future studies should account for SHS exposure when examining the association between smoking and colorectal cancer.
Smoking; Secondhand smoke exposure; Colorectal cancer; Case–control