To investigate whether nurse monitoring and protocol management of physical symptoms alleviates fatigue

Patients were randomized to receive either usual care or nurse management patient-tailored treatment using treatment management protocols. In the experimental group, nurse specialists recorded interventions for multiple physical symptoms. During outpatient meetings with the nurse, symptom severity was monitored. When any symptoms were rated ≥ 4 on an 11-point scale, the nurse referred the patient to the oncologist for further assessment and initiation of treatment according to palliative care guidelines, such as medication adjustment, other referrals, or other interventions. Nurses managed as many symptoms independently as possible. Highly specific interventions for pain, nausea, vomiting, constipation, diarrhea, anorexia, dyspnea, cough, and dry mouth were used. No specific interventions aimed at fatigue were identified. Patients met with the nurse at 1, 2–4, 5–7, and 8–10 weeks. Study assessments were done via mail at baseline and one, two, and three months.

• The study reported on a sample of 137 patients.
• Mean patient age was 58 years.
• The sample was 59% female and 41% male.
• Multiple solid tumor types were represented, with breast, gastrointestinal, and urogenital being the most common.
• Seventy-eight percent of patients were married or living with a partner, with more intervention group patients in this group.
• All patients were Caucasian.
• Average time since cancer diagnosis was 57 months.
• Patients were not eligible if they had a level of anxiety or depression requiring referral for psychiatric care or cognitive impairment.

• Single site
• Outpatient setting
• The Netherlands

A randomized controlled trial design was used.

• Numeric rating scale (NRS) to assess symptoms on 0–10 scale
• Multidimensional Fatigue Inventory (MFI)
• EORTC Quality of Life Questionnaire (QLC-30)
• Brief Fatigue Inventory (BFI)
• Hospital Anxiety and Depression Scale (HADS)

Patients reported that the most troublesome symptoms were pain, dyspnea, and anorexia. Patients had a median of two symptoms with NRS scores of at least 4 at baseline. MFI scores for general fatigue declined significantly over time in the intervention group compared to controls, with effect size ranging from 0.26 to 0.35 (p = 0.01). NRS fatigue scores also demonstrated decline compared to usual care controls (p < 0.001). BFI scores were not reported. Overall symptom burden was reported to decrease over time in the intervention group, while there was no change in controls (maximal effect size = 0.64, p = 0.002). Anxiety decreased in the intervention group compared to controls (maximal effect size = 0.32, p < 0.001).

Findings suggest that comprehensive management and monitoring for symptom control by nurse specialists was effective in reducing anxiety and fatigue in patients with cancer.

• The study had baseline sample/group differences of import.
• The study had risk of bias due to no blinding and no appropriate attentional control condition.
• Unintended interventions or applicable interventions were not described that would influence results.
• The study used selective outcomes reporting.
• Measurement/methods were not well described.
• Participant withdrawals were ≥ 10%.
• At baseline, fewer control patients were married or partnered, and there was no analysis of significance of baseline differences. This support difference could have influenced results.
• BFI measures were not reported, causing one to question if findings were not consistent for changes in fatigue.
• Calculation of “total symptom burden” was not described.
• Patients who withdrew were more anxious and depressed than those who remained in the study.

Findings suggest that continued symptom management and monitoring with a protocol approach can be effective for reducing symptoms overall, and reducing fatigue and anxiety. There were no specific intervention approaches identified that were used for fatigue, so the suggestion is that reducing other symptoms can have a positive impact on fatigue. There were also no specific interventions identified for anxiety, but anxiety also declined over time. These results suggest that ongoing monitoring and attention to patients alone may positively impact these symptoms.

To evaluate the efficacy of doxycycline in the prevention of erlotinib-induced rash (folliculitis) in patients with non-small cell lung cancer (NSCLC)

Patients were randomized via a computer website to receive either erlotinib 150 mg/d per os or erlotinib 150 mg/d per os plus 100 mg/d of doxycycline. Doxycycline began on day 0 (day of randomization) and was continued for four months and as long as 12 months at the primary investigator's discretion. Erlotinib began on day 1 and was administered for as long as 12 months or beyond or until disease progression or intolerable toxicity. Patients were evaluated on days 14 and 28 and at months 2, 4, 7, 10, and 12. Patients with grade 2 or higher folliculitis received treatment as appropriate.

• N = 147   
• MEAN AGE = 64 years (SD = 11)
• MALES: 67%, FEMALES: 33% 
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Patients with NSCLC 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients being treated with erlotinib, patients aged 18 years or older, patients with histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IIIB/IV) NSCLC, patients who had failed first-line platinum-based chemotherapy, measurable disease was according to response Evaluation Criteria in Solid Tumors, patients who had an Eastern Cooperative Oncology Group (ECOG) performance status of less than 2 (e.g., scale from 0 [fully active] to 4 [completely disabled]), patients who had adequate organ function and an estimated life expectancy of 12 weeks or longer

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Lausanne, Switzerland, and 23 sites in France

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

Open-label, randomized, prospective, phase II trial

• Skin efficacy—anonymous photographs were analyzed by a committee of blinded expert dermatologist using Common Terminology Criteria for Adverse Events (CTCAE) grading.
• Tumor response—Response Evaluation Criteria in Solid Tumors (RECIST)
• Quality of life—Dermatology Life Quality Index (DLQI)
• Compliance—daily doses of erlotinib and doxycycline were collected at each study time point.
• Adverse events—graded according to CTCAE, version 3.0

FOLLICULITIS: During the first four months of treatment, 52 patients (71%) in the doxycycline arm and 59 patients (81%) in the control arm developed folliculitis (p = 0.18). The mean duration of folliculitis was similar in both treatment arms (no p value given). Sixty-two percent of patients in the intervention arm developed grade 1 folliculitis compared to 19% in the control arm. Grade 3 folliculitis developed in 4% of patients in the intervention arm and 19% in the control arm (p < 0.001).

Doxycycline did not reduce the incidence of erlotinib-induced folliculitis but significantly reduced its severity. In fact, more patients in the intervention arm developed grade 1 folliculitis compared to the control arm. The duration of folliculitis was similar in both the intervention and control arm in this study. Compliance with erlotinib was higher in the doxycycline arm during the whole treatment period.

• Risk of bias (sample characteristics)
• Risk of bias (due to open label)
• More males than females in study
• The authors did not report on possible statistical differences in sample characteristics.

Nurses can collaborate with physicians to verify that doxycycline is combined with erlotinib treatment to improve the level of toxicity of folliculitis. Doxycycline has the potential to decrease the severity of folliculitis in patients with NSCLC who are receiving erlotinib. It does not, however, reduce the incidence of folliculitis in these patients during the first four months of treatment with erlotinib, nor does it reduce the duration of folliculitis.

STUDY PURPOSE: To evaluate if a dose response effect of exercise on inflammation and fatigue in cancer survivors exists

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED =  31 included in meta-regression 
• TOTAL PATIENTS INCLUDED IN REVIEW = 3,816
• SAMPLE RANGE ACROSS STUDIES: 16–500
• KEY SAMPLE CHARACTERISTICS: Participants had various tumor types, and the study included individuals in and post active treatment with chemotherapy and/or radiotherapy and/or surgery.

PHASE OF CARE: Multiple phases of care

Exercise interventions included aerobic, resistance, flexibility, and combinations of these. Interventions included supervised, unsupervised, home-based, hospital- or other setting–based, and group or individual exercise sessions. Moderate quality evidence that exercise had a positive effect on fatigue compared to usual care existed (standard mean deviation = 0.32, 95% confidence interval [0.13, 0.52]). A combination of aerobic and resistance provided the largest treatment effect. Aerobic intensity was negatively related to treatment effect. No relationships existed between resistance exercise and treatment effect.

Exercise has a beneficial effect on fatigue. Moderate intensity exercise appears to be most beneficial.

Varied study quality and sample sizes

This analysis adds to the body of evidence that exercise has a beneficial effect on fatigue among patients with cancer. This study suggests that moderate level aerobic exercise is more beneficial than more intense exercise. This information can be used to guide patient counseling and teaching to incorporate moderate exercise into daily routines.

A uniform NCCN consensus determined that recommendations were appropriate (NCCN Category of Evidence and Consensus = 2A).

Some interventions that may be useful to improve or maintain cognitive function might not be included in these guidelines because this manuscript did not detail search strategies, inclusions and exclusions, or the number of articles included in the recommendations.

The NCCN cognitive function algorithm aids healthcare professionals considering the assessment and treatment of cancer-related cognitive function. Nonpharmacologic interventions should be recommended to oncology survivors experiencing cognitive issues. Pharmacologic interventions may be considered when medical conditions permit and potential contributing factors are ruled out or managed.

STUDY PURPOSE: To conduct a systematic review of the research evidence for the effects of Radix Astragali (RA)–based Chinese herbal medicine in the prevention and treatment of oxaliplatin-induced peripheral neuropathy (PN)

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 24 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,552
• SAMPLE RANGE ACROSS STUDIES: 40–135; average size = 66
• KEY SAMPLE CHARACTERISTICS: 11 trials inpatients (n = 689); no setting identified for the other 13 trials (n = 863); 24 trials = 58.63% were male; colorectal cancer (n = 1,033); gastric cancer (n = 399); lung/breast/other cancers (n = 52), not specified (n = 68); range for total OXALI dose in all studies = 130 mg/m²–800 mg/m²; range for total OXALI dose in 11 trials 260–600 mg/m²

PHASE OF CARE: Not specified or not applicable; cannot determine if studies were in palliative care setting

APPLICATIONS: Elder care

• Fifteen RCTs comparing RA-based combined remedies to no intervention significantly reduced CIPN occurrence (n = 993 patients, odds ratio [OR] = 0.19, 95% CI confidence interval [0.14, 0.25], p < 0.01).
• One RCT comparing RA-based prescription to mecobalamin reduced CIPN occurrence (n = 42 patients, OR = 0.17, 95% CI [0.03, 0.94], p < 0.05).
• Two RCTs comparing RA-based prescription in addition to reduced glutathione versus calcium/magnesium infusions with the same conventional medications reduced CIPN occurrence (n = 120 patients, OR = 0.42, 95% CI [0.18, 0.97], p < 0.05).
• Fourteen RCTs comparing RA-based intervention versus no intervention significantly reduced the incidence of high-grade PN (11 trials used Levi’s grading) (n = 931 patients, OR = 0.17, 95% CI [0.09, 0.31], p < 0.01). No significant difference was found in the two trials comparing RA to mecobalamin or the two trials comparing RA to reduced glutathione or calcium/magnesium infusion with the same conventional medications. 
• Three RCTs comparing RA-based prescriptions and mecobalamin to mecobalamin alone found significant effect for RA-based prescription and mecobalamin in relieving CIPN (n = 213 patients, OR = 4.84, 95% CI [2.38, 9.83], p < 0.01).
• Six RCTs reported that the TA-based intervention significantly improved sensory nerve conduction velocity (MD = 4.42 m/s, 95% CI [3.27, 5.57], p < 0.01). No difference existed in motor nerve conduction velocity.
• No adverse events were reported in the 24 included studies for RA-based interventions. No consistent data was reported for quality of life, with only two trials including quality of life improvement after RA-based interventions.
• Funnel plots did not indicate publication bias.
• Effect sizes were not reported.

This meta-analysis indicated that RA-based interventions may provide potential benefit for oxaliplatin-induced PN. Although this meta-analysis did not show significant heterogeneity for different trial results, it did show considerable heterogeneity in the variables, treatments, and outcome measures studied. Studies included RA-based interventions with no reliable measures of drug composition, varied drug doses, self-made drug preparations, or RA combined with herbal compositions with variation in drug delivery methods. Therefore, it is premature to interpret these results as beneficial because of the substantial limitations for reliability and validity of the study results.

• Limited search
• High heterogeneity
• Low sample sizes
• Predominant yield of studies from only two databases: CNKI and Wanfang
• Safety, adverse event, or quality of life not used in search terms
• Twenty-four RCTs included three different CIPN grading scales.
• More than 50% of RA-based prescriptions included other herbal substances.
• No consistent reliable measure of drug composition
• Ten of the 24 RCTs had self-made prescriptions.
• Different RCT comparators (i.e., intervention, no intervention)
• More RCTs comparing RA-based prescription versus no intervention
• Doses/administration/duration of RA treatment different (oral = 10 RCTs, topical = 12 RCTs, IV = 1 RCT)
• Unclear phase of care or previous neurotoxic chemotherapy exposures
• Differences in duration of chemotherapy exposures and accumulated OXALI doses
• No multicenter large scale trials
• Effect sizes were not reported.

It remains unclear if RA provides benefit in alleviating oxaliplatin-induced PN. Additional RCTs are required to evaluate the reliable preparations of RA to investigate its full effects isolated in simple form versus its combined effect with other herbs. The effect of RA on the antitumor activity of oxaliplatin or other chemotherapeutic agents needs further study. Large multisite RCTs are needed to further evaluate drug safety in all phases of treatment and to identify the most effective dose, delivery method, duration of treatment, and quality of life.

Compare the immediate and long-term effects of true acupuncture versus sham acupuncture on hot flash frequency in women with breast cancer

The study included 72 women with breast cancer experiencing three or more hot flashes per day.

Patients were randomly assigned to receive either true or sham acupuncture.

The primary outcome measurement was hot flash frequency. Participants completed a hot flash diary for one day at days 7, 14, 21, 28, and 35.

The mean number of hot flashes per day was reduced from 8.7 to 6.2 in the true acupuncture group. The mean number of daily hot flashed was reduced from10.0 to 7.6 in the sham group. The true acupuncture was associated with 0.8 fewer hot flashes per day when compared to the sham at six weeks. This difference was not statistically significant. During the cross-over phase, participants in the sham group who received true acupuncture reported a further reduction in the frequency of hot flashes. The overall reduction in hot flash frequency persisted for up to 6 months after the completion of treatment.

The study was limited by a reliance on self-report instruments and recall. No physiologic measurements were used. The study may not have been of a sufficiently long duration and employed a modest sample size.

To determine if acupuncture reduced cancer-related fatigue (CRF) more effectively than did sham acupuncture.

Patients were randomized to an acupuncture or sham control group. Treatments were given once a week over six weeks. In the acupuncture group, a total of 14 needles were inserted at defined points during each session. The needles were stimulated manually and retained for 20 minutes. Sham needles, used in the control group, were blunt-tipped, moved up inside their handles when pressed against the skin, and did not penetrate the skin. In the control group, sham needles were applied in the same number and using the same technique as were the needles in the acupuncture group. Outcome measures were obtained at two weeks and at one week prior to the start of interventions and again at 42 and 49 days after completion.

• The study reported a sample of 74 patients (82% female, 18% male).
• Mean patient age was 53.5 years (range 45–59).
• Patients had multiple tumor types, and more than half had breast cancer.
• All had completed a course of chemotherapy at least 60 days prior to the study.

• Single site
• Outpatient
• Memorial Sloan Kettering Cancer Center, New York City, NY

Patients were undergoing the transition phase after initial treatment.

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

• Brief Fatigue Inventory (BFI)
• Hospital Anxiety and Depression Scale (HADS)
• Functional Assessment of Cancer Therapy-General (FACT-G)

• At least 87% of participants completed all sessions.
• In both groups, total fatigue scores declined by approximately one point between baseline and follow-up.
• There were no differences between groups.
• Neither HADS nor FACT-G measures showed significant differences between groups.

The study showed that acupuncture had no effect on the symptoms of fatigue, anxiety, or depression.

• The study had a small sample size, with less than 100 participants.
• The drop-out rate was greater than 24%.
• The authors performed an intention-to-treat analysis, but they did not report their exact procedures.

The study did not demonstrate that acupuncture had an effect on fatigue, anxiety, or depression. The study contributes to a growing body of research that shows conflicting results regarding the effectiveness of this intervention for the management of fatigue. It has been shown that symptoms such as fatigue and anxiety tend to decline over time among patients with cancer. It is unclear if the timing in this study affected the results; symptoms may have declined with or without the intervention.

To compare, in thorascopy patients, the efficacy of intrapleural bupivacaine versus that of PCA fentanyl

All patients underwent a thorascopic operation during the study. Afterward, the F group received IV fentanyl (F) by means of patient-controlled analgesia (PCA). The IB group received intermittent intrapleural bolus delivery of bupivacaine plus fentanyl. The CB group received continuous intrapleural delivery of bupivacaine plus fentanyl.

PCA fentanyl was given as 40 mcg/hour basal rate with 30 mcg every 10 min as needed to a 160 mcg/hour maximum. Patients in the IB  group received an initial bolus of 0.25% bupivacaine and the same PCA fentanyl dosage as the fentanyl-only group. If the fentanyl escalation was insufficient, the patient was prescribed additional 50 mcg boluses as needed. Patients in the CB group received 5 ml/hour continuous infusion bupivacaine via chest tube as well as PCA fentanyl. In the CB group, if fentanyl escalation was insufficient, 15–30 mg ketorolac was administered intervenously.

Nurses obtained baseline pain measures at the first postoperative complaint of pain and request for additional analgesia. Pain was also measured at 6, 12, 18, and 24 hours after the operation.

• The sample was composed of 30 patients.
• In the F group, mean patient age was 56 years. In the IB group, mean patient age was 61 years. In the CB group, mean patient age was 60.
• Of all patients, 56.6% were female and 43.3% were male. All patients underwent, during the study, thorascopic operations to achieve nonanatomic lung resections. Of all patients, 80% had cancer.

• Single setting
• Inpatient
• Roswell Park Cancer Institute, Buffalo, New York

Nonblinded prospective randomized controlled trial

• Visual analog pain score (VAPS)
• Amount of fentanyl used

• During the first six hours, authors noted a statistically significant difference (p = 0.01) among groups in total fentanyl consumed. Patients in the intrapleural infusion groups had lower consumption.
• At six hours, three patients in the fentanyl-only group were not able to bring pain to an acceptable level (p = 0.04).
• Compared to the F group, more patients in both intrapleural groups required dose escalation. The continuous bupivacaine group contained the highest proportion of patients needing escalation (p = 0.08).
• Authors noted no differences in the proportion of patients whose pain improved from baseline, and the highest pain severity scores were similar across groups.

Administering local anesthetic through a chest tube catheter can reduce fentanyl consumption and pain after a thoracoscopy.

• The study had a small sample size, with fewer than 100 patients.
• Patients' relatively brief length of stay suggests that cases involved may have been carefully selected, subjecting the sample to bias.

Intrapleural bupivacaine can be used to reduce pain after a thoroscopy; however, this approach may require ongoing adjustment and dosage escalations to achieve sufficient pain control. Intrapleural infusion may reduce total opioid consumption and attendant side effects; however, the study evidenced no differences in terms of prevalence or severity of effects. The most appropriate and effective doses of intrapleural bupivacaine remain unclear. Authors note that the continuous intrapleural infusion approach is much more costly than the other interventions. Whether study findings warrant the increased cost is unclear.

The objective of the study was to compare tunneled pleural catheter drainage (TCD) to bedside talc pleurodesis (TP) via chest catheter for efficacy in controlling symptomatic unilateral malignant pleural effusions (MPE).

Randomized patients received one of two methods (TP or TCD) for pleural drainage then were followed up for 60 days. For the TP procedure, a single dose of 4–5 g of sterile talc slurry in 100 mL of saline was infused into the pleural space with a chest catheter. Placement was confirmed on a chest x-ray. Talc was administered within 36 hours of tube placement. The tube remained clamped for two hours for talc distribution. When the chest drainage decreased to 150 mL/24 hours, pleurodesis was assumed and the tube was removed. TP was performed on an inpatient basis. For TCD, catheters were drained daily with drainage bottles. No more than 1,000 mL were drained at a time, other than during the initial drainage. A chest x-ray was taken within 36 hours of initial drainage and the patient, a caregiver, or a visiting nurse drained the catheter daily after that. The catheter was removed when the drainage volume was less than 30 mL each day over three consecutive days. TCD is generally an outpatient procedure.

• The sample was comprised of 57 patients aged 60–67 years.
• Of the 57 patients, 45%–55% were males and 39%–61% were females.
• Patients had a performance status of 0 to 2 with no active pleural infection, talc allergy, or other indications to talc use.
• Lung cancer (62%) and breast cancer (12%) were the most common malignancies.
• The study originally planned 530 total patients for 90% power to detect differences in efficacy between the two methods of pleural drainage.
• Trapped lung was not recommended for randomized therapy, as TCD may be a better therapy option.

The study was conducted in 21 comprehensive cancer centers—17 cases were conducted at one instution, and 1–7 cases were conducted at each of the other institutions.

• Patients were undergoing multiple phases of care.
• The study has clinical applicability for elder care and palliative care.

The study was a prospective, randomized phase III trial.

• Lung re-expansion was determined by the treating physician using serial chest x-rays.
• Condensed Memorial Symptom Assessment Scale form (specific elements: performance status, dyspnea scale, physical function, social life, and overall quality of life) measured quality of life and specific symptoms or functionality.

• No statistical differences in lung expansion were noted between the two treatment arms, but it improved from baseline in both cases.
• The odds ratio for TCD success was five times higher than TP, and patients with good expansion experienced better success (odds ratio, 5; 95% CI, 1–25; P = .053).
• Pleurodesis occurred in 86.2% of patients treated with TP, compared with 68.0% of those treated with TCD (P = .1883).
• Therapy-related complications were low but were higher in the TCD arm.
• Recurrent dyspnea was seen only in TP cases, and dyspnea was statistically better in patients treated with TCD (8.7 vs. 5.9; P = .036) even after adjusting for baseline dyspnea score, initial drainage, gender, inpatient status, and performance status at baseline.
• No relationship was seen between baseline dyspnea score and lung expansion at any of the three points; however, 30-day dyspnea-free exercise and all quality-of-life measures correlated significantly with lung expansion.

• TCD is preferred for patients with complicated effusions or when the lung may be trapped.
• Although TCD prolongs therapy, this added duration may maintain lung expansion and improve quality-of-life parameters.
• Lung expansion may be an unreliable indicator of the benefits of pleural drainage.
• TCDs in this study may more predictably relieve dyspnea.
• The study had to be closed early because patients had a strong preference for treatment (inpatient vs. outpatient) and refused randomization.

• The study had a small sample size of less than 100 patients.
• The study had a risk of bias because of no blinding and its sample characteristics.
• Accrual was far less than anticipated due to patient preferences interfering with patient consent to randomization.
• Refusals to participate may have influenced the final study population, as evidenced by lower-than-anticipated success of talc pleurodesis intervention.
• The study does not describe that “malignant effusion” was validated cyopathologically.

• TCD and TP are both common strategies to manage malignant pleural effusion.
• Similar lung expansion appears to be able to be achieved with both techniques in patients with uncomplicated pleural effusion, and the selection of method may be based upon patient preference.
• Nurses should ensure that patients are thoroughly informed of therapeutic options to make the best decision for their circumstances.
• In cases in which patients experience distress form dyspnea at baseline, they may experience better symptom relief with the TCD method of managing malignant pleural effusions.