Abstract Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac ...toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies including combination therapy with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Thirty percent to 90% of cancer survivors report impaired sleep quality post-treatment, which can be severe enough to increase morbidity and mortality. Lifestyle interventions, such as exercise, are ...recommended in conjunction with drugs and cognitive behavioral therapy for the treatment of impaired sleep. Preliminary evidence indicates that yoga-a mind-body practice and form of exercise-may improve sleep among cancer survivors. The primary aim of this randomized, controlled clinical trial was to determine the efficacy of a standardized yoga intervention compared with standard care for improving global sleep quality (primary outcome) among post-treatment cancer survivors.
In all, 410 survivors suffering from moderate or greater sleep disruption between 2 and 24 months after surgery, chemotherapy, and/or radiation therapy were randomly assigned to standard care or standard care plus the 4-week yoga intervention. The yoga intervention used the Yoga for Cancer Survivors (YOCAS) program consisting of pranayama (breathing exercises), 16 Gentle Hatha and Restorative yoga asanas (postures), and meditation. Participants attended two 75-minute sessions per week. Sleep quality was assessed by using the Pittsburgh Sleep Quality Index and actigraphy pre- and postintervention.
In all, 410 survivors were accrued (96% female; mean age, 54 years; 75% had breast cancer). Yoga participants demonstrated greater improvements in global sleep quality and, secondarily, subjective sleep quality, daytime dysfunction, wake after sleep onset, sleep efficiency, and medication use at postintervention (all P ≤ .05) compared with standard care participants.
Yoga, specifically the YOCAS program, is a useful treatment for improving sleep quality and reducing sleep medication use among cancer survivors.
Cancer-related fatigue (CRF) is a debilitating syndrome that persists for many cancer survivors for years after treatment. Symptoms include early and persistent fatigue, functional decline, ...depression, and cognitive difficulties. Inflammation, assessed using pro-inflammatory biomarkers, is increased in cancer survivors with fatigue and treatments for fatigue are often aimed at reducing inflammation. Additionally, cancer and its treatment lead to nutritional complications, changes in body composition, and nutritional deficiencies that potentially weaken the cancer survivor and impact CRF. We conducted a qualitative review of clinical trials that assessed nutritional interventions for preventing and treating CRF. Further studies were examined that used nutritional interventions to address inflammation and fatigue, due to the dearth of nutrition research directly related to CRF. Dietary intake prior to, during, and after cancer treatment appears to affect fatigue levels. Increased protein intake may help preserve lean mass and body composition. Dietary patterns that reduce inflammation, such as the Mediterranean diet and other plant-based diets, appear tolerable to cancer survivors and may reduce fatigue. Supplementation with ginseng, ginger, or probiotics may improve cancer survivors' energy levels. Nutritional interventions, alone or in combination with other interventions should be considered as therapy for fatigue in cancer survivors.
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DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Cancer-related fatigue (CRF) remains one of the most prevalent and troublesome adverse events experienced by patients with cancer during and after therapy.
To perform a meta-analysis to establish and ...compare the mean weighted effect sizes (WESs) of the 4 most commonly recommended treatments for CRF-exercise, psychological, combined exercise and psychological, and pharmaceutical-and to identify independent variables associated with treatment effectiveness.
PubMed, PsycINFO, CINAHL, EMBASE, and the Cochrane Library were searched from the inception of each database to May 31, 2016.
Randomized clinical trials in adults with cancer were selected. Inclusion criteria consisted of CRF severity as an outcome and testing of exercise, psychological, exercise plus psychological, or pharmaceutical interventions.
Studies were independently reviewed by 12 raters in 3 groups using a systematic and blinded process for reconciling disagreement. Effect sizes (Cohen d) were calculated and inversely weighted by SE.
Severity of CRF was the primary outcome. Study quality was assessed using a modified 12-item version of the Physiotherapy Evidence-Based Database scale (range, 0-12, with 12 indicating best quality).
From 17 033 references, 113 unique studies articles (11 525 unique participants; 78% female; mean age, 54 range, 35-72 years) published from January 1, 1999, through May 31, 2016, had sufficient data. Studies were of good quality (mean Physiotherapy Evidence-Based Database scale score, 8.2; range, 5-12) with no evidence of publication bias. Exercise (WES, 0.30; 95% CI, 0.25-0.36; P < .001), psychological (WES, 0.27; 95% CI, 0.21-0.33; P < .001), and exercise plus psychological interventions (WES, 0.26; 95% CI, 0.13-0.38; P < .001) improved CRF during and after primary treatment, whereas pharmaceutical interventions did not (WES, 0.09; 95% CI, 0.00-0.19; P = .05). Results also suggest that CRF treatment effectiveness was associated with cancer stage, baseline treatment status, experimental treatment format, experimental treatment delivery mode, psychological mode, type of control condition, use of intention-to-treat analysis, and fatigue measures (WES range, -0.91 to 0.99). Results suggest that the effectiveness of behavioral interventions, specifically exercise and psychological interventions, is not attributable to time, attention, and education, and specific intervention modes may be more effective for treating CRF at different points in the cancer treatment trajectory (WES range, 0.09-0.22).
Exercise and psychological interventions are effective for reducing CRF during and after cancer treatment, and they are significantly better than the available pharmaceutical options. Clinicians should prescribe exercise or psychological interventions as first-line treatments for CRF.
Cancer-related cognitive impairment (CRCI) is an important clinical problem in patients with breast cancer receiving chemotherapy. Nationwide longitudinal studies are needed to understand the ...trajectory and severity of CRCI in specific cognitive domains.
The overall objective of this nationwide, prospective, observational study conducted within the National Cancer Institute Community Clinical Oncology Research Program was to assess trajectories in specific cognitive domains in patients with breast cancer (stage I-IIIC) receiving chemotherapy, from pre- (A1) to postchemotherapy (A2) and from prechemotherapy to 6 months postchemotherapy (A3); controls were assessed at the same time-equivalent points. The primary aim assessed visual memory using the Cambridge Neuropsychological Test Automated Battery Delayed Match to Sample test by longitudinal mixed models including A1, A2, and A3 and adjusting for age, education, race, cognitive reserve score, and baseline anxiety and depressive symptoms. We also assessed trajectories of CRCI in other aspects of memory as well as in attention and executive function with computerized, paper-based, and telephone-based cognitive tests.
In total, 580 patients with breast cancer (mean age, 53.4 years) and 363 controls (mean age, 52.6 years) were assessed. On the Delayed Match to Sample test, the longitudinal mixed model results revealed a significant group-by-time effect ( P < .005); patients declined over time from prechemotherapy (A1) to 6 months postchemotherapy (A3; P = .005), but controls did not change ( P = .426). The group difference between patients and controls was also significant, revealing declines in patients but not controls ( P = .017). Several other models of computerized, standard, and telephone tests indicated significantly worse performance by patients compared with controls from pre- to postchemotherapy and from prechemotherapy to 6 months postchemotherapy.
This nationwide study showed CRCI in patients with breast cancer affects multiple cognitive domains for at least 6 months postchemotherapy.
Cannabis has the potential to modulate some of the most common and debilitating symptoms of cancer and its treatments, including nausea and vomiting, loss of appetite, and pain. However, the dearth ...of scientific evidence for the effectiveness of cannabis in treating these symptoms in patients with cancer poses a challenge to clinicians in discussing this option with their patients. A review was performed using keywords related to cannabis and important symptoms of cancer and its treatments. Literature was qualitatively reviewed from preclinical models to clinical trials in the fields of cancer, human immunodeficiency virus (HIV), multiple sclerosis, inflammatory bowel disease, post-traumatic stress disorder (PTSD), and others, to prudently inform the use of cannabis in supportive and palliative care in cancer. There is a reasonable amount of evidence to consider cannabis for nausea and vomiting, loss of appetite, and pain as a supplement to first-line treatments. There is promising evidence to treat chemotherapy-induced peripheral neuropathy, gastrointestinal distress, and sleep disorders, but the literature is thus far too limited to recommend cannabis for these symptoms. Scant, yet more controversial, evidence exists in regard to cannabis for cancer- and treatment-related cognitive impairment, anxiety, depression, and fatigue. Adverse effects of cannabis are documented but tend to be mild. Cannabis has multifaceted potential bioactive benefits that appear to outweigh its risks in many situations. Further research is required to elucidate its mechanisms of action and efficacy and to optimize cannabis preparations and doses for specific populations affected by cancer.
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.
Patients with prostate cancer on androgen deprivation therapy often suffer rapid bone loss during the initiation of treatment. Supplementation with high‐dose vitamin D (50,000 IU/week plus 800 IU/day) significantly and safely decreased the amount of bone loss compared with vitamin D supplementation using the recommended daily allowance (800 IU/day).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
Up to 38 % of prostate cancer survivors experience significant psychological distress; 6–16 % are diagnosed with depression or anxiety disorders. Support from a relationship partner can ...ameliorate psychological distress, but many studies treat relationship status as a dichotomous predictor without accounting for level of support provided by the partner.
Methods
The current study is a secondary analysis of a sample of 292 prostate cancer survivors recruited by nine Community Clinical Oncology Program (CCOP) sites around the USA to a larger randomized controlled trial. Self-reported distress was measured at a baseline visit using the Profile of Mood States (POMS) and partner support was measured using the Social Network and Support Assessment (SNSA). Post hoc groups consisting of unmarried survivors, married survivors with low partner support (SNSA scores below the median), and married survivors with high partner support (SNSA scores above the median) were compared on distress using univariate and analysis of covariance (ANCOVA) analyses.
Results
Married prostate cancer survivors with high partner support reported significantly lower levels of psychological distress than the other two groups on the total distress scale (16.20–19.19 points lower,
p
< 0.001). After adjusting for multiple comparisons, this pattern was also seen for subscales of distress.
Conclusions
This study highlights the importance of assessing both partner support and marital status when evaluating a survivor’s psychosocial functioning and support network.
Implications for Cancer Survivors
Assessing support could improve understanding of the association between partner support and prostate cancer survivors’ psychological distress and could lead to interventions to bolster support and reduce distress.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Abstract
Background
Cancer-related cognitive decline (CRCD) is an important clinical problem, but limited research exists on assessment of cognitive function in patients with lymphoma.
Methods
The ...overall objective of this nationwide, prospective, observational study conducted in the National Cancer Institute Community Clinical Oncology Research Program (NCORP) was to assess changes in memory, attention, and executive function in patients with lymphoma from pre- (A1) to postchemotherapy (A2) and to 6 months postchemotherapy (A3). Individuals without cancer served as noncancer controls, paired to patients by age and sex, and assessed at the same time-equivalent points. Longitudinal linear mixed models (LMM) including A1, A2, and A3 and adjusting for age, education, race, sex, cognitive reserve score, baseline anxiety, and depressive symptoms were fit. We assessed changes in patients compared with control participants without cancer and assessed differences in cognitive function in those patients with Hodgkin vs non-Hodgkin disease and by disease subtype. All statistical tests were 2-sided.
Results
Patients with lymphoma (n = 248) and participants without cancer serving as controls (n = 212) were recruited from 19 NCORP sites. From pre- to postchemotherapy and from prechemotherapy to 6 months follow-up, patients reported more cognitive problems over time compared with controls (Functional Assessment of Cancer-Therapy-Cognitive Function FACT-Cog perceived cognitive impairment effect size (ES) = 0.83 and 0.84 for A1 to A2 and A1 to A3, respectively; P < .001; single-item cognitive symptoms ES range = 0.55 to 0.70 inclusive of A1 to A2 and A1 to A3; P < .001); the complaints were more pronounced in women with lymphoma compared with men with lymphoma (FACT-Cog Perceived Cognitive Impairment (PCI) score group-by-time-by-sex interaction, P = .007). Patients with lymphoma also performed statistically significantly less well on tests of verbal memory and delayed recall, attention and executive function, and telephone-based category fluency.
Conclusion
Patients with lymphoma experience worse patient-reported and objectively assessed cognitive function from prechemotherapy to 6-month follow-up compared with age- and sex-paired controls without cancer assessed at similar time intervals.
Purpose
Breast cancer treatment is associated with weight gain, and obesity and its related cardiometabolic and hormonal risk factors have been associated with poorer outcomes. Dietary intervention ...may address these risk factors, but limited research has been done in the setting of metastatic breast cancer requiring systemic therapy.
Methods
Women with metastatic breast cancer on stable treatment were randomized 2:1 to an 8-week intervention (
n
= 21) or control (
n
= 11). The intervention included weekly assessment visits and an ad libitum whole-food, plant-based (WFPB) diet with provided meals. Cardiometabolic, hormonal, and cancer markers were assessed at baseline, 4 weeks, and 8 weeks.
Results
Within the intervention group, mean weight decreased by 6.6% (
p
< 0.01) after 8 weeks. Fasting insulin decreased from 16.8 uIU/L to 11.2 uIU/L (
p
< 0.01), concurrent with significantly reduced insulin resistance. Total cholesterol decreased from 193.6 mg/dL to 159 mg/dL (
p
< 0.01), and low-density lipoprotein (LDL) cholesterol decreased from 104.6 mg/dL to 82.2 mg/dL (
p
< 0.01). Total testosterone was unchanged, but free testosterone trended lower within the intervention group (
p
= 0.08) as sex hormone binding globulin increased from 74.3 nmol/L to 98.2 nmol/L (
p
< 0.01). There were no significant differences in cancer progression markers at week 8, although mean CA 15-3, CA 27.29, and CEA were lower in the intervention group (
p
= 0.53,
p
= 0.23, and
p
= 0.54, respectively) compared to control, when adjusted for baseline.
Conclusion
WFPB dietary changes during treatment for metastatic breast cancer are well tolerated and significantly improve weight, cardiometabolic and hormonal parameters. Longer studies are warranted to assess the durability of changes.
Trial registration
First registered at Clinicaltrials.gov (NCT03045289) on February 7, 2017.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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