High-dose vitamin D to attenuate bone loss in patients with prostate cancer on androgen deprivation therapy: A phase 2 RCT.

BACKGROUND: Androgen deprivation therapy (ADT) inhibits prostate cancer growth. However, ADT causes loss of bone mineral density (BMD) and an increase in fracture risk; effective interventions for ADT-induced bone loss are limited. METHODS: A phase 2 randomized controlled trial investigated the feasibility, safety, and preliminary efficacy of high-dose weekly vitamin D (HDVD, 50,000 IU/week) versus placebo for 24 weeks in patients with prostate cancer receiving ADT, with all subjects receiving 600 IU/day vitamin D and 1000 mg/day calcium. Participants were ≥60 years (mean years, 67.7), had a serum 25-hydroxyvitamin D level <32 ng/mL, and initiated ADT within the previous 6 months. At baseline and after intervention, dual-energy x-ray absorptiometry was used to assess BMD, and levels of bone cell, bone formation, and resorption were measured. RESULTS: The HDVD group (N = 29) lost 1.5% BMD at the total hip vs. 4.1% for the low-dose group (N = 30; p = .03) and 1.7% BMD at the femoral neck vs. 4.4% in the low-dose group (p = .06). Stratified analyses showed that, for those with baseline 25-hydroxyvitamin D level <27 ng/mL, the HDVD group lost 2.3% BMD at the total hip vs 7.1% for the low-dose group (p < .01). Those in the HDVD arm showed significant changes in parathyroid hormone (p < .01), osteoprotegerin (p < 0.01), N-terminal telopeptide of type 1 collagen (p < 0.01) and C-terminal telopeptide of type 1 collagen (p < 0.01). No difference in adverse events or toxicity was noted between the groups. CONCLUSIONS: HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25-hydroxyvitamin D levels, although demonstrating safety and feasibility in prostate cancer patients on ADT.

Fatigue, anxiety, and quality of life in breast cancer patients compared to non-cancer controls: a nationwide longitudinal analysis.

PURPOSE: Fatigue and anxiety are common and significant symptoms reported by cancer patients. Few studies have examined the trajectory of multidimensional fatigue and anxiety, the relationships between them and with quality of life. METHODS: Breast cancer patients (n = 580) from community oncology clinics and age-matched controls (n = 364) completed fatigue and anxiety questionnaires prior to chemotherapy (A1), at chemotherapy completion (A2), and six months post-chemotherapy (A3). Linear mixed models (LMM) compared trajectories of fatigue /anxiety over time in patients and controls and estimated their relationship with quality of life. Models adjusted for age, education, race, BMI, marital status, menopausal status, and sleep symptoms. RESULTS: Patients reported greater fatigue and anxiety compared to controls at all time points (p's < 0.001, 35% clinically meaningful anxiety at baseline). From A1 to A2 patients experienced a significant increase in fatigue (ß = 8.3 95%CI 6.6,10.0) which returned to A1 values at A3 but remained greater than controls' (p < 0.001). General, mental, and physical fatigue subscales increased from A1 to A2 remaining significantly higher than A1 at A3 (p < 0.001). Anxiety improved over time (A1 to A3 ß = - 4.3 95%CI -2.6,-3.3) but remained higher than controls at A3 (p < 0.001). Among patients, fatigue and anxiety significantly predicted one another and quality of life. Menopausal status, higher BMI, mastectomy, and sleep problems also significantly predicted change in fatigue. CONCLUSION: Breast cancer patients experience significant fatigue and anxiety up to six months post-chemotherapy that is associated with worse quality of life. Future interventions should simultaneously address anxiety and fatigue, focusing on mental and physical fatigue subdomains.

Utility of topical agents for radiation dermatitis and pain: a randomized clinical trial.

PURPOSE: Although topical agents are often provided during radiation therapy, there is limited consensus and evidence for their use prophylactically to prevent or reduce radiation dermatitis. METHODS: This was a multi-site, randomized, placebo-controlled, blinded study of 191 breast cancer patients to compare the prophylactic effectiveness of three topical agents (Curcumin, HPR Plus™, and Placebo) for reducing radiation dermatitis and associated pain. Patients applied the topical agent to their skin in the radiation area site three times daily starting the first day of radiation therapy (RT) until 1 week after RT completion. RESULTS: Of the 191 randomized patients, 171 patients were included in the final analyses (87.5% white females, mean age = 58 (range = 36-88)). Mean radiation dermatitis severity (RDS) scores did not significantly differ between study arms (Curcumin = 2.68 [2.49, 2.86]; HPR Plus™ = 2.64 [2.45, 2.82]; Placebo = 2.63 [2.44, 2.83]; p = 0.929). Logistic regression analyses showed that increased breast field separation positively correlated with increased radiation dermatitis severity (p = 0.018). In patients with high breast field separation (≥ 25 cm), RDS scores (Curcumin = 2.70 [2.21, 3.19]; HPR Plus™ = 3.57 [3.16, 4.00]; Placebo = 2.95 [2.60, 3.30]; p = 0.024) and pain scores (Curcumin = 0.52 [- 0.28, 1.33]; HPR Plus™ = 0.55 [- 0.19, 1.30]; Placebo = 1.73 [0.97, 2.50]; p = 0.046) significantly differed at the end of RT. CONCLUSIONS: Although there were no significant effects of the treatment groups on the overall population, our exploratory subgroup analysis suggests that prophylactic treatment with topical curcumin may be effective for minimizing skin reactions and pain for patients with high breast separation (≥ 25 cm) who may have the worst skin reactions.

Racial/Ethnic Differences in Comprehension of Biospecimen Collection: a Nationwide University of Rochester Cancer Center NCI Community Oncology Research Program Study.

To examine whether (a) non-minority participants differed from racial minority participants in the understanding of biospecimens collected for research purposes, (b) patients differed from comparison group in their understanding of the ways their biospecimens could be used by researchers, and (c) participants received adequate information before consenting to donate blood for research studies. We analyzed cross-sectional data from female breast cancer patients scheduled to receive chemotherapy at the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) clinical sites and a healthy comparison group. After reading a consent form related to biospecimens and consenting to participate in a clinical trial, participants' understanding of biospecimen collection was evaluated. Linear models were used to compare scores between non-minority and racial minority participants as well as cancer and non-cancer comparisons adjusting for possible confounding factors. A total of 650 participants provided evaluable data; 592 were non-minority (Caucasian) and 58 participants were a racial minority (71% Black and 29% other). There were 427 cancer patients and 223 comparisons. Non-minority participants scored higher than racial minorities on relevance-to-care items (diff. = 0.48, CI 0.13-0.80, p = 0.001). Comparison group scored higher than cancer patients on relevance-to-care items (diff. = 0.58, CI 0.37-0.78). A moderate number of the participants exhibited a poor understanding of biospecimen collection across all racial/ethnic backgrounds, but racial minority participants' scores remained lower in the relevance-to-care subscale even after adjusting for education and reading level. Differences were also noted among the patients and comparison group. Researchers should facilitate comprehension of biospecimen collection for all study participants, especially racial minority participants.

Systematic Review of Randomized Controlled Trials of Exercise Interventions Using Digital Activity Trackers in Patients With Cancer.

Background: Exercise can ameliorate cancer- and treatment-related toxicities, but poor adherence to exercise regimens is a barrier. Exercise interventions using digital activity trackers (E-DATs) may improve exercise adherence, but data are limited for patients with cancer. We conducted a systematic review examining the feasibility of E-DATs in cancer survivors and effects on activity level, body composition, objective fitness outcomes, health-related quality of life (HRQoL), self-reported symptoms, and biomarkers. Methods: We identified randomized controlled trials (RCTs) of E-DATs in adult cancer survivors published in English between January 1, 2008, and July 27, 2017. Two authors independently reviewed article titles (n=160), removed duplicates (n=50), and reviewed the remaining 110 articles for eligibility. Results: A total of 12 RCTs met eligibility criteria, including 1,450 patients (mean age, 50-70 years) with the following cancers: breast (n=5), colon or breast (n=2), prostate (n=1), acute leukemia (n=1), or others (n=3). Duration of E-DATs ranged from 4 to 24 weeks, and the follow-up period ranged from 4 to 52 weeks, with retention rates of 54% to 95%. The technology component of E-DATs included pedometers (n=8); pedometers with smartphone application (n=1), Wii Fit (n=1), heart rate monitor (n=1); and a wireless sensor with accelerometer, gyroscope, and magnetometer (n=1). Adherence by at least one measure to E-DATs was >70% in 8 of 8 RCTs. Compared with controls, E-DATs significantly improved patients' step count in 3 of 5 RCTs, activity level in 6 of 9 RCTs, and HRQoL in 7 of 9 RCTs (all P≤05), with no significant changes in biomarkers (eg, interleukin 6, tumor necrosis factor α, C-reactive protein, c-peptide, lipid panel) in 3 RCTs. Duration of E-DAT was not significantly correlated with adherence or study retention. Conclusions: This systematic review shows that E-DATs are feasible to implement in cancer survivors. Future research should examine the optimal type, dose, and schedule of E-DATs for cancer survivors.

Positive effects of acupressure bands combined with relaxation music/instructions on patients most at risk for chemotherapy-induced nausea.

PURPOSE: Research by our group has shown that acupressure bands are efficacious in reducing chemotherapy-induced nausea (CIN) for breast cancer patients who expect nausea, and that their effectiveness in controlling CIN can largely be accounted for by patients' expectations of efficacy, i.e., a placebo effect. The present research examined if the effectiveness of acupressure bands could be enhanced by boosting patients' expectation of the bands' efficacy. METHODS: Two hundred forty-two chemotherapy-naïve patients with breast cancer who expected nausea were randomized. Arms 1 and 2 received acupressure bands, plus a relaxation MP3 and written handout that were either expectancy-enhancing (arm 1) or expectancy-neutral (arm 2). Arm 3 was the control without bands or MP3 and received standard care. All participants received guideline-specified antiemetics. RESULTS: Peak CIN for arms 1, 2, and 3 on a 1-7 scale was 3.52, 3.55, and 3.87, respectively (p = 0.46). Because no differences were observed between arms 1 and 2 (primary analysis), we combined these two arms (intervention) and compared them to controls for the following analyses. A significant interaction was found between intervention/control and receiving doxorubicin-based chemotherapy (yes/no) and pre-treatment anxiety (high/low). Intervention patients receiving doxorubicin had lower peak CIN than controls (3.62 vs. 4.38; p = 0.02). Similarly, intervention patients with high pre-treatment anxiety had a lower peak CIN than controls (3.62 vs. 4.62; p = 0.01). CONCLUSIONS: In breast cancer patients undergoing chemotherapy and having high CIN expectation, acupressure bands combined with a relaxation recording were effective in reducing CIN for patients who received doxorubicin or had high anxiety.

Effects of exercise on inflammation in patients receiving chemotherapy: a nationwide NCORP randomized clinical trial.

PURPOSE: A growing body of research suggests that inflammation plays a role in many chemotherapy-related toxicities such as fatigue, anxiety, and neuropathy. Regular exercise can change levels of individual cytokines (e.g., reducing IL-6, increasing IL-10); however, it is not known whether exercise during chemotherapy affects relationships between cytokines (i.e., whether cytokine concentrations change collectively vs. independently). This study assessed how 6 weeks of exercise during chemotherapy affected relationships between changes in concentrations of several cytokines. METHODS: This is a secondary analysis of a randomized trial studying 6 weeks of moderate-intensity walking and resistance exercise during chemotherapy compared with chemotherapy alone. At pre- and post-intervention, patients provided blood to assess serum concentrations of cytokines IL-1ß, IL-6, IL-8, IL-10, and IFN-γ, and receptor sTNFR1. We investigated relationships between cytokines using the correlations between changes in cytokine concentrations from pre- to post-intervention. RESULTS: We obtained complete data from 293 patients (149 randomized to exercise). Exercise strengthened the correlation between concentration changes of IL-10 and IL-6 (r = 0.44 in exercisers vs. 0.11 in controls; p = 0.001). We observed the same pattern for IL-10:IL-1ß and IL-10:sTNFR1. Exercise also induced an anti-inflammatory cytokine profile, per reductions in pro-inflammatory IFN-γ (p = 0.044) and perhaps IL-1ß (p = 0.099, trend-level significance). CONCLUSIONS: Our hypothesis-generating work suggests that regular exercise during 6 weeks of chemotherapy may cause certain cytokine concentrations to change collectively (not independently). This work enhances our understanding of relationships between cytokines and complements traditional analyses of cytokines in isolation. Future work should test for replication and relationships to patient outcomes. TRIAL REGISTRATION: Clinical Trials.gov, # NCT00924651, http://www.clinicaltrials.gov .

Social Support, Insomnia, and Adherence to Cognitive Behavioral Therapy for Insomnia After Cancer Treatment.

OBJECTIVE/BACKGROUND: While cognitive-behavioral therapy for insomnia (CBT-I) has been shown to be efficacious in treating cancer survivors' insomnia, 30-60% of individuals have difficulty adhering to intervention components. Psychosocial predictors of adherence and response to CBT-I, such as social support, have not been examined in intervention studies for cancer survivors. PARTICIPANTS: Data from a randomized placebo-controlled 2 x 2 trial of CBT-I and armodafinil (a wakefulness promoting agent) were used to assess adherence. Ninety-six cancer survivors participated in the trial (mean age 56, 86% female, 68% breast cancer). METHODS: CBT-I and armodafinil were administered over the course of seven weeks, and participants were assessed at baseline, during intervention, postintervention, and at a three-month follow-up. Social support was assessed using a Functional Assessment of Chronic Illness Therapy subscale, insomnia severity was assessed using the Insomnia Severity Index, and adherence was measured based on CBT-I sleep prescriptions. RESULTS: At baseline, social support was negatively correlated with insomnia severity (r = -0.30, p = 0.002) and associations between social support, CBT-I, and insomnia were maintained through the three-month follow-up. Social support was positively associated with adherence to CBT-I during intervention weeks 3, 4, and 5, and with overall intervention adherence. At postintervention, both social support and treatment with CBT-I independently predicted decreased insomnia severity (p < 0.01) when controlling for baseline insomnia severity. CONCLUSIONS: Higher social support is associated with better intervention adherence and improved sleep independent of CBT-I. Additional research is needed to determine whether social support can be leveraged to improve adherence and response to CBT-I.

Multimedia psychoeducation for patients with cancer who are eligible for clinical trials: A randomized clinical trial.

BACKGROUND: Supporting patients' decision making about clinical trials may enhance trial participation. To date, few theory-based interventions have been tested to address this issue. The objective of the current study was aimed to evaluate the effect of a multimedia psychoeducation (MP) intervention, relative to a print education (PE) intervention, on patients' decision support needs and attitudes about clinical trials. METHODS: Patients with cancer who were eligible for participation in a National Cancer Institute therapeutic cancer clinical trial were recruited through the nationwide University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program from 2014 to 2016 and were randomized to the MP or PE intervention. Assessments at baseline (before intervention), postintervention, and at a 2-month follow-up visit included patients' decision support needs, attitudes regarding clinical trials, and clinical trial participation. RESULTS: In total, 418 patients with various types of cancer were recruited (ages 26-89 years). Relative to the PE intervention, the MP intervention did not significantly affect decision support needs. However, patients in the MP arm reported significantly more positive attitudes about clinical trials and were more likely to participate in a clinical trial than those in the PE arm (69% vs 62%; P = .01). Furthermore, an improvement in attitudes about clinical trials significantly mediated the effect of the intervention on participation in clinical trials. CONCLUSIONS: The MP intervention was able to improve patient attitudes toward clinical trials compared with the PE intervention, and this improvement led to increased rates of participation in trials. The MP intervention could be disseminated to improve attitudes about clinical trials among patients with cancer.

Community Oncologists' Decision-Making for Treatment of Older Patients With Cancer.

Background: This study's objectives were to describe community oncologists' beliefs about and confidence with geriatric care and to determine whether geriatric-relevant information influences cancer treatment decisions. Methods: Community oncologists were recruited to participate in 2 multisite geriatric oncology trials. Participants shared their beliefs about and confidence in caring for older adults. They were also asked to make a first-line chemotherapy recommendation (combination vs single-agent vs no chemotherapy) for a hypothetical vignette of an older patient with advanced pancreatic cancer. Each oncologist received one randomly chosen vignette that varied on 3 variables: age (72/84 years), impaired function (yes/no), and cognitive impairment (yes/no). Other patient characteristics were held constant. Logistic regression models were used to identify associations between oncologist/vignette-patient characteristics and treatment decisions. Results: Oncologist response rate was 61% (n=305/498). Most oncologists agreed that "the care of older adults with cancer needs to be improved" (89%) and that "geriatrics training is essential" (72%). However, <25% were "very confident" in recognizing dementia or conducting a fall risk or functional assessment, and only 23% reported using the geriatric assessment in clinic. Each randomly varied patient characteristic was independently associated with the decision to treat: younger age (adjusted odds ratio [aOR], 5.01; 95% CI, 2.73-9.20), normal cognition (aOR, 5.42; 95% CI, 3.01-9.76), and being functionally intact (aOR, 3.85; 95% CI, 2.12-7.00). Accounting for all vignettes across all scenarios, 161 oncologists (52%) said they would offer chemotherapy. All variables were independently associated with prescribing single-agent over combination chemotherapy (older age: aOR, 3.22; 95% CI 1.43-7.25, impaired cognition: aOR, 3.13; 95% CI, 1.36-7.20, impaired function: aOR, 2.48; 95% CI, 1.12-5.72). Oncologists' characteristics were not associated with decisions about providing chemotherapy. Conclusion: Geriatric-relevant information, when available, strongly influences community oncologists' treatment decisions.

Oral curcumin for radiation dermatitis: a URCC NCORP study of 686 breast cancer patients.

PURPOSE: Despite advances in medical technology, radiation dermatitis occurs in 95% of patients receiving radiation therapy (RT) for cancer. Currently, there is no standard and effective treatment for the prevention or control of radiation dermatitis. The goal of the study was to determine the efficacy of oral curcumin, one of the biologically active components in turmeric, at reducing radiation dermatitis severity (RDS) at the end of RT, using the RDS scale, compared to placebo. METHODS: This was a multisite, randomized, double-blinded, placebo-controlled trial of 686 breast cancer patients. Patients took four 500-mg capsules of placebo or curcumin three times daily throughout their prescribed course of RT until 1 week post-RT. RESULTS: A total of 686 patients were included in the final analyses (87.5% white females, mean age = 58). Linear mixed-model analyses demonstrated that curcumin did not reduce radiation dermatitis severity at the end of RT compared to placebo (B (95% CI) = 0.044 (- 0.101, 0.188), p = 0.552). Fewer curcumin patients with RDS > 3.0 suggested a trend toward reduced severity (7.4 vs. 12.9%, p = 0.082). Patient-reported changes in pain, symptoms, and quality of life were not statistically significant between arms. CONCLUSIONS: Oral curcumin did not significantly reduce radiation dermatitis severity compared to placebo. The skin rating variation and broad eligibility criteria could not account for the undetectable therapeutic effect. An objective measure for radiation dermatitis severity and further exploration for an effective treatment for radiation dermatitis is warranted.

Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial.

PURPOSE: Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms. METHODS: Cancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0-10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness. RESULTS: Exercise reduced CIPN symptoms of hot/coldness in hands/feet (-0.46 units, p = 0.045) and numbness and tingling (- 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076). CONCLUSIONS: Exercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients. TRIAL REGISTRATION: Clinical Trials.gov , # NCT00924651, http://www.clinicaltrials.gov .

Racial Differences in Information Needs During and After Cancer Treatment: a Nationwide, Longitudinal Survey by the University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program.

Before treatment, cancer patients need information about side effects and prognosis, while after treatment they need information to transition to survivorship. Research documenting these needs is limited, especially among racial and ethnic minorities. This study evaluated cancer patients' needs according to race both before and after treatment. We compared white (n = 904) to black (n = 52) patients receiving treatment at 17 National Cancer Institute Community Oncology Research Program (NCORP) sites on their cancer-related concerns and need for information before and after cancer treatment. Two-sample t test and chi-squared analyses were used to assess group differences. Compared to white patients, black patients reported significantly higher concerns about diet (44.3 vs. 25.4 %,) and exercise (40.4 vs. 19.7 %,) during the course of treatment. Compared to whites, blacks also had significantly higher concern about treatment-related issues (white vs. black mean, 25.52 vs. 31.78), self-image issues (7.03 vs. 8.60), family-related issues (10.44 vs. 12.84), and financial concerns (6.42 vs. 8.90, all p < 0.05). Blacks, compared to whites, also had significantly greater post-treatment information needs regarding follow-up tests (8.17 vs. 9.44), stress management (4.12 vs. 4.89), and handling stigma after cancer treatment (4.21 vs. 4.89) [all p < 0.05]. Pre-treatment concerns and post-treatment information needs differed by race, with black patients reporting greater information needs and concerns. In clinical practice, tailored approaches may work particularly well in addressing the needs and concerns of black patients.

Nausea and disturbed sleep as predictors of cancer-related fatigue in breast cancer patients: a multicenter NCORP study.

PURPOSE: Cancer-related fatigue (CRF) is a prevalent and distressing side effect of cancer and its treatment that remains inadequately understood and poorly managed. A better understanding of the factors contributing to CRF could result in more effective strategies for the prevention and treatment of CRF. The objectives of this study were to examine the prevalence, severity, and potential predictors for the early onset of CRF after chemotherapy cycle 1 in breast cancer patients. METHODS: We report on a secondary data analysis of 548 female breast cancer patients from a phase III multi-center randomized controlled trial examining antiemetic efficacy. CRF was assessed by the Brief Fatigue Inventory at pre- and post-chemotherapy cycle 1 as well as by the four-day diary. RESULTS: The prevalence of clinically relevant post-CRF was 75%. Linear regression showed that pre-treatment CRF, greater nausea, disturbed sleep, and younger age were significant risk factors for post-CRF (adjusted R2 = 0.39; P < 0.0001). Path modeling showed that nausea severity influenced post-CRF both directly and indirectly by influencing disturbed sleep. Similarly, pre-treatment CRF influenced post-CRF directly as well as indirectly through both nausea severity and disturbed sleep. Pearson correlations showed that changes in CRF over time were significantly correlated with concurrent changes in nausea severity (r = 0.41; P < 0.0001) and in disturbed sleep (r = 0.20; P < 0.0001). CONCLUSION: This study showed a high prevalence (75%) of clinically relevant CRF in breast cancer patients following their initial chemotherapy, and that nausea severity, disturbed sleep, pre-treatment CRF, and age were significant predictors of symptom.

Modafinil Moderates the Relationship Between Cancer-Related Fatigue and Depression in 541 Patients Receiving Chemotherapy.

OBJECTIVE: The aim of this study was to examine the effect of modafinil on depression via a secondary data analysis of a randomized clinical trial of modafinil for fatigue in cancer patients. The primary aim is to elucidate factors that contributed to the effectiveness of modafinil in the parent trial. METHODS: Five hundred forty-one cancer patients receiving chemotherapy and experiencing fatigue (Brief Fatigue Inventory [BFI] item 3 of ≥3) were randomized to receive 200 mg modafinil (n = 260) or placebo (n = 281) daily from baseline (cycle 2) to posttest (cycle 4). Patients completed the Center for Epidemiological Studies-Depression Scale (CES-D) and Profile of Mood States depression-dejection subscale at baseline and posttest. We used linear regression to address the hypothesis that modafinil would be associated with reduced depression, particularly in those experiencing severe fatigue (BFI ≥7). RESULTS: Modafinil did not have a significant effect on depression, even for those patients with severe fatigue. However, for subjects with severe fatigue (BFI ≥7), those receiving modafinil had lower depression scores than did control subjects. Modafinil significantly moderated the relationship between baseline fatigue and CES-D total scores (P = 0.04) and was marginally significant as a moderator for the relationship between baseline fatigue and Profile of Mood States depression-dejection subscale scores (P = 0.07). Modafinil also significantly moderated the relationship between baseline fatigue and CES-D positive affect subscale scores (P = 0.003), but not CES-D somatic, negative affect, or interpersonal subscale scores. CONCLUSIONS: Modafinil differentially impacts depression based on a patient's level of fatigue and reduced depressive symptoms only in those with extreme fatigue. This effect may be driven by increases in positive affective symptoms. These results have significant implications for intervention; in patients with high levels of fatigue, modafinil might also reduce depression. Future randomized clinical trials are needed to confirm these results.

Cognitive behavioral therapy for insomnia, but not armodafinil, improves fatigue in cancer survivors with insomnia: a randomized placebo-controlled trial.

PURPOSE: Fatigue is a prevalent, distressing side effect of cancer and cancer treatment which commonly coexists with insomnia. Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve insomnia in cancer patients, but less is known about its ability to impact fatigue. This work is the analysis for a secondary aim of a four-arm randomized controlled trial (RCT) study assessing the combined and comparative effect of CBT-I and a wakefulness-promoting agent, armodafinil (A), to improve sleep and daytime functioning in cancer survivors. Herein, we examine the effect of CBT-I, with and without A, on fatigue in cancer survivors. PATIENTS AND METHODS: This study was a four-arm factorial study with CBTI-I (yes/no) versus A (yes/no). It consisted of 96 cancer survivors (average age 56 years; 88 % female; 68 % breast cancer). Fatigue was assessed by the brief fatigue inventory (BFI) and the FACIT-Fatigue scale. The analysis assessed the additive effects of CBT-I and A and possible non-additive effects where the effect of CBT-I changes depending on the presence or absence of A. RESULTS: Analyses adjusting for baseline differences showed that CBT-I improved fatigue as measured by two separate scales (BFI: P = 0.002, Std. error = 0.32, effect size (ES) = 0.46; FACIT-Fatigue: P < 0.001, Std. error = 1.74, ES = 0.64). Armodafinil alone did not show a statistically significant effect on fatigue levels (all Ps > 0.40) nor did the drug influence the efficacy of CBT-I. Structural equation analysis revealed that reductions in insomnia severity were directly responsible for improving cancer-related fatigue. CONCLUSIONS: CBT-I with and without armodafinil resulted in a clinically and statistically significant reduction of subjective daytime fatigue in cancer survivors with chronic insomnia. Armodafinil did not improve cancer-related fatigue (CRF) and did not change the efficacy of CBT-I. Patients reporting CRF should be screened and, if indicated, treated for insomnia as part of a comprehensive fatigue management program.

Buspirone for management of dyspnea in cancer patients receiving chemotherapy: a randomized placebo-controlled URCC CCOP study.

PURPOSE: Cancer-related dyspnea is a common, distressing, and difficult-to-manage symptom in cancer patients, resulting in diminished quality of life and poor prognosis. Buspirone, a non-benzodiazepine anxiolytic which does not suppress respiration and has proven efficacy in the treatment of generalized anxiety disorder, has been suggested to relieve the sensation of dyspnea in patients with COPD. The main objective of our study was to evaluate whether buspirone alleviates dyspnea in cancer patients. METHODS: We report on a randomized, placebo-controlled trial of 432 patients (mean age 64, female 51%, lung cancer 62%) from 16 participating Community Clinical Oncology Program (CCOP) sites with grade 2 or higher dyspnea, as assessed by the Modified Medical Research Council Dyspnea Scale. Dyspnea was assessed by the Oxygen Cost Diagram (OCD; higher scores are better) and anxiety by the state subscale of the State-Trait Anxiety Inventory (STAI-S; lower scores are better) at baseline and after the 4-week intervention (post-intervention). RESULTS: Mean scores from baseline to post-intervention for buspirone were OCD 8.7 to 9.0 and STAI-S 40.5 to 40.1 and for placebo were OCD 8.4 to 9.3 and STAI-S 40.9 to 38.6 with raw improvements over time on both measures being greater in the placebo group. Analysis of covariance (ANCOVA) controlling for baseline scores showed no statistically significant difference between groups for OCD (P = 0.052) or STAI-S (P = 0.062). CONCLUSION: Buspirone did not result in significant improvement in dyspnea or anxiety in cancer patients. Thus, buspirone should not be recommended as a pharmacological option for dyspnea in cancer patients.

A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study of 462 cancer survivors.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) occurs in as high as 70% of patients receiving certain types of chemotherapy agents. The FDA has yet to approve a therapy for CIPN. The aim of this multicenter, phase III, randomized, double-blind, placebo-controlled trial was to investigate the efficacy of 2% ketamine plus 4% amitriptyline (KA) cream for reducing CIPN. METHODS: Cancer survivors who completed chemotherapy at least 1 month prior and had CIPN (>4 out of 10) were enrolled (N=462). CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average "pain, numbness, or tingling in [their] hands and feet over the past 24 h" on an 11-point numeric rating scale at baseline and 6 weeks post intervention. ANCOVA was used to measure differences in 6-week CIPN with effects including baseline CIPN, KA treatment arm, and previous taxane therapy (Y/N). RESULTS: The KA treatment showed no effect on 6-week CIPN scores (adjusted mean difference=-0.17, p=0.363). CONCLUSIONS: This study suggests that KA cream does not decrease CIPN symptoms in cancer survivors.

Characterization of skin reactions and pain reported by patients receiving radiation therapy for cancer at different sites.

BACKGROUND: Skin reactions and pain are commonly reported side effects of radiation therapy (RT). OBJECTIVE: To characterize RT-induced symptoms according to treatment site subgroups and identify skin symptoms that correlate with pain. METHODS: A self-report survey-adapted from the MD Anderson Symptom Inventory and the McGill Pain Questionnaire--assessed RT-induced skin problems, pain, and specific skin symptoms. Wilcoxon Sign Ranked tests compared mean severity or pre- and post-RT pain and skin problems within each RT-site subgroup. Multiple linear regression (MLR) investigated associations between skin symptoms and pain. RESULTS: Survey respondents (N = 106) were 58% female and on average 64 years old. RT sites included lung, breast, lower abdomen, head/neck/brain, and upper abdomen. Only patients receiving breast RT reported significant increases in treatment site pain and skin problems (P < or = .007). Patients receiving head/neck/brain RT reported increased skin problems (P < .0009). MLR showed that post-RT skin tenderness and tightness were most strongly associated with post-RT pain (P = .066 and P = .122, respectively). LIMITATIONS: Small sample size, exploratory analyses, and nonvalidated measure. CONCLUSIONS: Only patients receiving breast RT reported significant increases in pain and skin problems at the RT site while patients receiving head/neck/brain RT had increased skin problems but not pain. These findings suggest that the severity of skin problems is not the only factor that contributes to pain and that interventions should be tailored to specifically target pain at the RT site, possibly by targeting tenderness and tightness. These findings should be confirmed in a larger sampling of RT patients.