STUDY PURPOSE: To assess whether integrative management of colorectal cancer, in which traditional medicines are added to oxaliplatin regimens, reduced the incidence of chemotherapy-induced nausea and vomiting (CINV) and to determine if specific particular traditional medicines provided enough evidence to pursue further research for CINV

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 27 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,843
• SAMPLE RANGE ACROSS STUDIES: 16–74 patients
• KEY SAMPLE CHARACTERISTICS: Adult patients from China and Australia with a colorectal diagnosis

PHASE OF CARE: Active antitumor treatment

Across all 27 studies, the test groups showed significantly reduced CINV (RR = 0.65) with an absolute risk reduction of 24% compared to controls. They further divided test groups into an injection group and an oral administration group. Four different injection products were tested in six studies, with an overall RR of 0.73 in the traditional medicine plus oxaliplatin group. In the oral administration, 21 studies were analyzed, which contained 98 different plant-based ingredients with an average of 12 ingredients per traditional medicine intervention. The oral agents demonstrated an overall reduction in CINV with a RR of 0.62. The absolute risk reduction was 25% for the test groups compared to controls. In addition, each plant was analyzed individually as well as in all combinations (2, 3, 4, 5, 6, and 7 plants). The results demonstrated that six plants influenced the relative risk for CINV, including atractylodes, poria, coix, glycyrrhiza, astragalus, and panax ginseng.

This meta-analysis of 27 studies suggested the potential benefit of adding traditional medicines in the reduction of CINV associated with oxaliplatin-based chemotherapy in adults with colorectal cancer. The lack of blinding in most studies may have led to an overestimation of the effects on CINV. Sensitivity analysis identified six plants that were associated with significant reductions in CINV, which may warrant further clinical research.

• No quality evaluation
• Low sample sizes
• Most studies were not blinded and did not have a placebo for the control groups, which is likely to influence participant-reported CINV. The use of antiemetics also may have affected study results. No dosing information on treatment regimens were used other than the inclusion of oxaliplatin. Most studies were small single institutions studies, and the methodological reporting of the quality of studies and randomization was weak.

In this meta-analysis of traditional medicine interventions in adult patients with colorectal cancer receiving oxaliplatin-based therapies, six plants demonstrated reductions in CINV. Although the studies had limitations related to methodology, no serious adverse events or increase in CINV occurred. These plants warrant further research and consideration in patients whose CINV is not well-controlled by conventional therapies.

STUDY PURPOSE: To investigate the effectiveness of massage in reducing cancer-related pain

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 3
• TOTAL PATIENTS INCLUDED IN REVIEW = 278
• SAMPLE RANGE ACROSS STUDIES: 14–115 patients
• KEY SAMPLE CHARACTERISTICS: No details were provided.

PHASE OF CARE: Not specified or not applicable
 
APPLICATIONS: Palliative care

The pooled standard mean difference was 0.01, showing no effect of aromatherapy massage compared to usual care for reduction in pain.

Findings do not show that aromatherapy massage is effective in reducing pain.

• Limited search
• Limited number of studies included
• Low sample sizes

Overall, mixed evidence existed regarding effects of massage therapies for pain management among patients with cancer. This analysis did not show effectiveness of aromatherapy massage, but was very limited by the small number of studies included and small study samples. Massage is a low-risk intervention that may be beneficial for some patients.

To assess the effects of a 12-week walking program on improving subjective and objective sleep quality and rest-activity rhythms in patients with lung cancer

Home-based walking exercise at moderate intensity and weekly exercise counseling were provided. Participants were given detailed instruction according to a manual for the exercise program, including determination of intensity, pulse monitoring, rating perceived exertion, prevention of injury, and conditions requiring termination of the exercise program. Weekly exercise-related phone counseling was provided to reinforce teaching and encourage continued participation. The usual care control group was given typical services and asked to maintain normal activity and not perform additional exercise. Exercise counseling was offered to the usual care group at the end of the study. An actigraph was worn by patients to collect data continuously for 72 hours.

• N = 111, 89 assessed at six months
• MEAN AGE = 63.6 years
• AGE RANGE = 37–83 years
• MALES: 44.1%, FEMALES: 55.9%
• CURRENT TREATMENT: Combination radiation and chemotherapy, other
• KEY DISEASE CHARACTERISTICS: All had surgery for lung cancer, and most were receiving radiation and chemotherapy. Most had stage I disease.
• OTHER KEY SAMPLE CHARACTERISTICS: Eighty-two percent were married. Patients were an average of 454 days since diagnosis.

• SITE: Single-site   
• SETTING TYPE: Home    
• LOCATION: Taiwan

PHASE OF CARE: Multiple phases of care

Randomized, controlled trial

• Pittsburgh Sleep Quality Index (PSQI)
• Actigraphy for evaluation of rest activity parameters, sleep parameters, and physical activity

Overall participants completed 58.2% of all planned exercise sessions. The usual care group showed a higher mean amount of moderate physical activity at all time points when measured (37–46 minutes per day compared to 38–10 minutes per day at three and six months). No significant difference over time was reported between groups. The walking exercise group had improved PSQI scores over time compared to the usual care group (p = 0.001). No differences between groups in objective measures of sleep quality existed, except that total sleep time at six months was higher in the exercise group (p = 0.023).

Sleep quality measures showed improvement in the study group compared to the controls; however, given that the average amount of moderate intensity exercise was higher in the control group, the impact of walking exercise versus counseling is unclear.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Key sample group differences that could influence results
• Measurement/methods not well described
• Subject withdrawals ≥ 10%
• It was stated that baseline minutes of moderate activity differed significantly between study groups; however, data were not provided, and the direction of difference is unknown.

The effect of exercise on sleep quality in patients with insomnia remains unclear from this study. Although measures showed improvement in the walking exercise group compared to the controls, the amount of moderate intensity exercise was actually higher in the control group. This does not point to the impact of exercise on differences seen in this study.

The purpose of this study was to evaluate effects of antibiotic-coated central venous catheters as compared to non-coated central venous catheters on the development of catheter-associated blood stream infection.

Data was retrospectively analyzed from December 1, 2003 through August 31, 2006 at an inpatient center for patients treated with interleukin-2. Prior to December 2004, non-coated tunneled catheters (NC-C)  were used in these patients; antibiotic-coated catheters were used after December 2004. The coated catheters contained minocycline and rifampin (M/R-C) in their coating. All patients received antibiotic prophylaxis. Cases of catheter-related infection were retrospectively analyzed and compared between the two groups. Catheter insertion and line care remained the same for both groups independent of the type of catheter inserted.

• The study reviewed 78 and 107 episodes of catheter use.
• The age range of studied participants was 26–66 years.
• Sixty-one percent of reviewed participants were diagnosed with melanoma and renal cell carcinoma.
• Non-coated catheters were used in 77 episodes, and M/R-C-coated catheters were used in 30 episodes. All patients received IV nafcillin (67%), clindamycin (15%), or levofloxacin (13%) during high-dose interleukin-2 for 48 hours afterwards.

A single-site inpatient setting.

Active treatment

Retrospective descriptive

• Catheter colonization was defined as the isolation of 15 colony-forming units (CFU) of any microorganism from a catheter tip or subcutaneous segment; or any organism from a blood culture drawn through the catheter during routine surveillance in the absence of fever.
• Local catheter-related infection was defined as exit site infection as demonstrated by purulent drainage from the catheter site.
• Probable catheter-related bacteremia (CRB) was defined as the presence of an indwelling central venous catheter (CVC) with at least one positive blood culture from the peripheral vein, with clinical manifestations of infection.
• Definite CRB was defined as the presence of an indwelling CVC with at least one positive blood culture from the peripheral vein, manifestations of infection, and no apparent source for the blood stream infection except the catheter. Response to treatment was defined as the resolution of all clinical and microbiological manifestations of catheter-related infection, and failure to treatment was defined as persistence of the clinical signs and symptoms of the infection and positive microbiological data.
   

A total of nine episodes of CRB were identified (six were probable and three definite), all in patients with NC-C (M/R-C 0% versus NC-C 12%; p = 0.06). In three of the nine episodes of bacteremia, the blood cultures grew more than one pathogen and in all nine cases, the prophylactic antibiotic had no activity against the pathogen. The causative pathogens for CRB included methicillin-resistant, coagulase-negative infections. There was one episode of probable catheter-related candidemia (Candidaparapsilosis) in a patient with a coated catheter, while two episodes of catheter colonization secondary to coagulase-negative Staphylococci occurred in two patients who had no signs or symptoms of infection.

Based on the data presented, there is potential benefit to an antibiotic-coated catheter compared with a non-coated catheter.

• Small sample (less than 100 participants)
• Only 30 cases with coated catheters
• Retrospective design

No recommendations can be made on the basis of this study alone. Antibiotic-coated, short-term CVCs may be helpful in preventing catheter-associated bloodstream infections.

To systematically review studies that have prescribed progressive resistance training (PRT) in breast cancer

Databases searched were PubMed, Medline, CINAHL, SportDiscus, Embase, and Web of Science. Search keywords were breast cancer, oncology, malignancy, neoplasm, tumor, mastectomy, lumpectomy, radiotherapy, chemotherapy, and exercise training, training, physical activity, rehabilitation, resistance training, aerobic training, strength training, lifestyle, muscle, endurance, and strength. Studies were included if they

• Had a patient population of adults aged 18 years or older diagnosed and surgically treated for malignancy of the breast
• Prescribed PRT in isolation or in combination with other exercise modalities (e.g., aerobic training) after breast cancer surgery, adjuvant therapies (i.e., radiotherapy or chemotherapy), or any other time after breast cancer treatment
• Evaluated outcomes potentially responsive to chronic PRT, including a broad spectrum of physiological, functional, and psychological outcome measures.

Studies were excluded if they investigated the effects of single, acute bouts of PRT, prescribed movement exercises without loading against a resistance, or prescribed PRT before breast cancer treatment.
 

The total number of studies initially reviewed was 12. The Delphi List was used as the method of study evaluation.
 

• The number of studies included in the report was 10.
• The total sample size across studies was 538, with a range of less than 20 to 242.
• Patients were female and being treated for breast cancer stages 0–III.
• Some patients had lymphedema.
• Patient age ranged from 25–78 years.
• Most patients were post-menopausal.
• The majority of patients received intervention after chemotherapy or radiation.

The study included a broad spectrum of physiological (body compositions, including reduced sum of five skinfolds, reduced waist and hip circumferences, reduced percent body fat, and increased muscle mass) , functional (improved upper-body strength, increased upper-body muscular endurance, increased flexibility of the ipsilateral (surgical) and contralateral shoulder joint, and improvements of lower-body strength) and psychological (improved aspects of quality of life, depression, and mood) outcome measures. Lymphedema incidence secondary to exercise programs was tracked as an adverse event in six studies. There was no incidence or exacerbation of lymphedema or improvements in lymphedema attributed to the exercise regimens.

Women surgically treated for breast cancer can derive health-related and clinical benefits by performing PRT after breast cancer surgery. No exacerbation or improvement of objectively measured or subjectively reported lymphedema symptoms were reported.

PRT should be advocated among oncologists and in community care settings.

STUDY PURPOSE: To assess the safety and efficacy of progressive resistance training in patients with breast cancer with attention to effects on lymphedema

• FINAL NUMBER STUDIES INCLUDED = 15
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,652
• SAMPLE RANGE ACROSS STUDIES: 21–232 patients
• KEY SAMPLE CHARACTERISTICS: Mean age ranged from 26–62 years

PHASE OF CARE: Multiple phases of care

For the five studies included in the meta-analysis (654 patients), the odds ratio for the incidence or exacerbation of lymphedema was 0.53 (95%, CI = 0.31–0.9). PRT did not change arm volume or patient-reported severity as shown by an analysis of standard mean differences. Five studies reported no adverse events, and other studies reported temporary muscle soreness or minor musculoskeletal injuries. There was no significant heterogeneity. PRT produced a small, nonsignificant improvement in quality of life (SMD = 0.17). Overall, PRT improved upper and lower body muscle strength. Ten studies used machines or free weights for training.

Progressive resistance training did not induce or exacerbate arm lymphedema in women with breast cancer, and it was not associated with any severe adverse events.

Some included studies were done in women without lymphedema, and the risk of development was not clear from data in this review.

The findings of this meta-analysis suggested that progressive resistance training is safe in women with breast cancer and does not induce or exacerbate arm lymphedema. Women do not need to avoid lifting weight to prevent the exacerbation of lymphedema.

The purpose of the study was to evaluate the neuropathy-protective effects of calcium and magnesium infusions in patients receiving oxaliplatin.

Patients were randomized to a treatment group with calcium gluconate 1 g plus 1 g of magnesium sulfate in 100 ml normal saline infused before and after oxaliplatin, or a placebo group with infusions of normal saline.

• The sample consisted of 19 participants with a mean age of 54 years.
• The amount of men (52%) slightly outnumbered the amount of women (48%).
• All of the participants had colorectal cancer and were receiving oxaliplatin-based chemotherapy with a life expectancy of more than three months.
• Exclusion criteria included previous treatment with platinum-based chemotherapy and/or a preexisting neurologic disease or metastases.
• Seventy-eight percent of the patients received 600 mg/m² of oxaliplatin.
• The median follow-up was 8.7 months.

The study was conducted in a single-site location in Singapore.

• Active treatment
• Late effects

The study was a blinded, placebo-controlled, randomized phase II design.

Measurements included the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0] and oxaliplatin-specific toxicity scale nerve conduction studies.

Incidence of grade 1 and 2 neurotoxicity was higher in the placebo group, but there was a higher proportion of grade 3 cumulative numbness in the treatment group. No differences were noted between groups for tingling and cold sensitivity. In addition, no difference was noted in time to onset of symptoms. Conduction studies showed lower median score at the end of the study in the treatment arm (p = 0.02). Of note, the study was ended prematurely.

This study does not provide strong evidence regarding the efficacy of calcium and magnesium infusion for the reduction of chemotherapy-associated peripheral neuropathy.

• A small sample size (less than 30 participants).
• Findings and reported conclusions can be confusing since median end of study nerve conduction scores suggested increased abnormal conduction in the treatment group, as noted by the authors.
• A correlation between nerve conduction findings and subjective patient symptoms are unclear.
• No information was provided regarding chemotherapy treatment delays or dose reductions.
• Given the question of cumulative effects, it may be more useful to look at symptoms at oxaliplatin dose levels rather than time.

Because of a small sample size, this current study does not provide strong evidence regarding use of calcium and magnesium infusions. Neuropathic symptom effects appear to be mixed, with higher prevalence of grade 3 with treatment, but overall prevalence lower with treatment. Some symptoms appear to be affected and some do not, and the relationship between nerve conduction findings and symptoms are unclear. Additional research in this area is needed to clarify the actual impact of calcium and magnesium for protective effects with neurotoxic treatment.

To assess the impact of adding rolapitant to standard antiemetics (5-HT₃ receptor antagonists and dexamethasone) on the daily lives of patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC)

This is a secondary analysis study of three clinical trials (phase III experimental studies). Patients were stratified by sex and randomly assigned (1:1) to either single oral dose rolapitant 180 mg or placebo 1–2 hours prior to chemotherapy. All patients received 5-HT₃ receptor antagonists and dexamethasone. Quality of life was assessed by patients by completing the 18-item Functional Living Index-Emesis (FLI-E) questionnaire on day 6 of cycle 1.

• N = 2,402 (1,070 patients in the pooled HEC studies and 1,332 patients in the MEC/AC)   
• AGE: Between 18–90 years
• MALES: 39.1% (938 patients), FEMALES: 60.9% (1,464 patients)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Various malignancies; a Karnofsky performance score of 60 or greater; a predicted life expectancy of four months or greater; and adequate bone marrow, kidney, and liver function
• OTHER KEY SAMPLE CHARACTERISTICS: Aged older than 18 years, naïve to their scheduled HEC/MEC

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Canada

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care

Three double-blind, phase III, randomized, controlled longitudinal trials (specified analyses [MEC/AC study]), and pooled post hoc analyses (HEC studies)

Treatment comparisons were performed between the FLI-E questionnaire total score and nausea and vomiting domain scores, in addition to the end point of no impact on daily life.

Data were analyzed for all randomized patients in the modified intent-to-treat population. Patients in the rolapitant group reported a significantly higher FLI-E total score than patients in the control group in the pooled HEC studies (confidence interval [CI] [2.6, 7.9], p < 0.001) and in the MEC/AC study (CI [1.7, 6.5], p < 0.001). A significant improvement in the nausea domain score was observed with rolapitant versus control in the pooled HEC studies (CI [0.2, 3.4], p = 0.02) and the MEC/AC study (CI [0.3, 3.3], p = 0.019), as well as the vomiting domain score in the pooled HEC studies (CI [2.1, 4.7], p < 0.001) and the MEC/AC study (CI [1.1, 3.4], p < 0.001).

This secondary analysis study demonstrated the efficacy of adding rolapitant to standard antiemetics in reducing the negative delayed impact of CINV on the daily lives of patients receiving HEC or MEC.

• Baseline sample/group differences of import
• Secondary analysis data from three experimental clinical trials
• Included patient with various cancers

Nurses should be aware of the additional benefit of adding an NK₁ receptor antagonist to the treatment of patients with cancer receiving HEC and MEC.

To determine the effect of OHR118 on appetite, early satiety, and nutritional intake in patients with advanced cancer experiencing anorexia or anorexia-cachexia syndrome

Patients received 4.0 ml of OHR118 via subcutaneous injection daily for 28 days. Patients who benefited were offered the option to continue for a total of 56 days.

• The study reported on a sample of 11 patients with cancer experiencing anorexia or anorexia-cachexia syndrome.
• Mean patient age was 63 years, with a range of 18–80 years.
• The sample was 71% male and 29% female.
• Patients were diagnosed with lung, pancreatic, colorectal, gastric, prostate, or head and neck cancer.
• Of the sample, 27% of patients had stage III disease and 73% had stage IV disease.

• The study site was not specified, but the authors were from the Division of Palliative Care at the University of Ottawa, so it appears that the study was Canadian and done at a single site.
• The nature of the intervention would suggest an outpatient setting.

• Patients were undergoing the active treatment, end-of-life, or long-term follow-up phase of care.
• The study has clinical applicability for late effects and survivorship, and end-of-life and palliative care.

• A prospective, observational study design was used.
• Patients were not randomized, nor was there a control group.
• Neither patients nor researchers were blinded.

• Patient-Generated Subjective Global Assessment (PG-SGA)
• Edmonton Symptom Assessment Scale (ESAS)
• Dyspepsia Symptom Severity Index (DSSI)
• Simmonds Functional Assessment (SFA)
• Bodystat 1500 (lean body mass and body composition measurement)
• Harpenden Skinfold Caliper (skinfold thickness measurement)

Eleven patients completed the first 28 days of the study, and 6 completed the second 28 days. Results from the first 28 days demonstrated a statistically significant improvement of appetite (p = 0.01) and depression (p = 0.05) on the ESAS. All other ESAS items did not show a statistically significant improvement. The overall PG-SGA score measuring nutrition (weight loss, nutrition impact symptoms, intake, and functional capacity) was significantly reduced (p = 0.01). The DSSI showed statistically significant results for the items of frequent burping or belching (p = 0.02), feeling full after meals (p = 0.04), and abdominal distention (p = 0.03). The sit-to-stand item on the SFA was statistically significant (p = 0.01) for deterioration of ability.

The authors concluded that OHR118 showed improvements consistent with previous work done in a \"very positive\" larger study in the AIDS population, and that this translates to \"improved patient comfort and quality of life.\"

Of the many values measured with the multiple measurement tools, only the general PG-SGA score, appetite, frequent belching, feeling full after meals, and abdominal distention showed statistically significant improvement. The study did not meet the secondary endpoints of changes in performance status, lean muscle mass, or quality of life.

• The authors concluded that the depression item on the ESAS was significant with a p value of 0.05; however, their preanalysis value of significance had been determined to be less than 0.05. They then went on to state in their discussion that improving appetite would improve depression, which their study demonstrated. The significant findings of decreased depression were challenging to interpret because of the statistical methods used in analysis and should be interpreted with caution.
• Of the initial 21 patients recruited, 10 dropped out, 5 had disease progression or died, 2 had abdominal pain, 1 had a phobia of needles, and 2 refused to continue citing no reason. There was no control group, and it is not clear from the study how patients were recruited.
• The abstract states that eight patients continued to 56 days; however, the manuscript analysis says that six completed the 56 days.
• It is not clear if OHR118 is an approved agent.

This study should be interpreted with caution because it was small, with limited statistically significant results to support the research objective.

To compare the efficacy of nebulized hydromorphone, systemic hydromorphone, and nebulized saline for incident dyspnea in patients with advanced cancer.

On three occasions when patients requested treatment for incident breathlessness, they randomly received one of the following:

• 5 mg of nebulized hydromorphone
• A systemic breakthrough dose of hydromorphone
• 3 mL of nebulized saline and an agent to maintain double blinding.

If patients felt the intervention was not effective, they could ask for additional pharmaceutical interventions. Patients scored breathlessness at 10, 20, 30, and 60 minutes from completion of treatment. Treatment order was randomized.

• The sample was comprised of 20 patients (11 men, 9 women) receiving palliative care.
• Mean age was 69 years (range 48–83). 
• Diagnoses included primary lung cancer or secondary lung pathology, including lung metastases, pleural effusion, or pulmonary emboli.
• To be eligible, patients had to have Mini Mental State Exam (MMSE) results of at least 24 out of 30.
• Thirteen patients were on continuous oxygen.
• Mean baseline total opioid dose in morphine equivalent mg was 82 (range 10–540).

• Inpatient- and community-based hospice service in Brisbane, Australia
• Single site

Patients were undergoing the palliative and end of life phases of care.

The study was a pilot, double-blind, randomized, crossover, controlled trial.

• Perceived intensity of breathlessness was measured on a vertical 100-mm visual analog scale (VAS).
• Pulse rate and peripheral oxygen saturation were measured with a pulse oximeter.
• Respiratory rate was counted by the research nurse over two 30-second intervals.

There were no differences between treatments in improvement scores. Improvement in breathlessness at 10 minutes post intervention completion was seen in each of the treatment conditions. Improvement considered to be clinically significant (≥1 cm on the VAS) was only seen with the nebulized hydromorphone. Respiratory rate improved over time from 10 to 60 minutes (p < 0.05), with no difference between treatments. There were no clear, consistent preferences among patients for any particular intervention.

The results suggest that nebulized saline provides relief of incident breathlessness; its effect is ongoing and does not differ significantly from the effects of nebulized opioid treatments.

• The study was appropriately powered to answer the study questions, but the study had a small sample size.
• A change of 1 cm on the VAS was used as a clinically significant symptom change, in concert with the work of others.
• Further research to define clinically significant differences in patient perception would be beneficial.
• It is not clear if higher doses of hydromorphone might yield differences across groups.
• The authors suggested that improvements in respiratory rates and peripheral oxygen over time likely represent Type I error in this study because the patients had a background of irreversible baseline dyspnea.
• The presence of the research nurse, to specifically administer this protocol, may have had an effect in terms of reassuring patients and confounded the overall results. Similar research having patients self-administer treatments might address this aspect.
• It is unclear if findings represent placebo effects.