STUDY PURPOSE: To evaluate the evidence regarding beneficial and adverse effects of pharmacologic treatment of neuropathic cancer pain

TYPE OF STUDY: Systematic review

DATABASES USED: PubMed and EMBASE before August 2012; additional studies were identified from study reference lists.

KEYWORDS: Complete search terms are provided.

INCLUSION CRITERIA: Studies involving adult patients with cancer receiving oral analgesics

EXCLUSION CRITERIA: Not specified

TOTAL REFERENCES RETRIEVED = 653

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: American Academy of Neurology evidence classification was used. Authors calculated the absolute risk benefit as the number of patients who received 30%–50% improvement divided by the total number of patients in the treatment group. The fraction of patients who dropped out because of adverse events also was determined. Pain reduction scores were calculated as the percentage of pain reduction from baseline in the study.

• FINAL NUMBER STUDIES INCLUDED = 30
• SAMPLE RANGE ACROSS STUDIES = 1–218
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,267
• KEY SAMPLE CHARACTERISTICS: Not provided

APPLICATIONS: Palliative care

The proportion of patients who obtained improvement of pain with antidepressants was 0.55 (95% CI 0.40–0.69), with anticonvulsants was 0.57 (95% CI 0.44–0.69), with opioids was 0.95 (95% CI 0.93–0.96), and with other adjuvant medications was 0.45 (95% CI 0.33–0.57). Effects for patients with mixed pain were similar. The proportion of patients who withdrew because of adverse effects was 12.6% with antidepressants, 5% with anticonvulsants, 6% with opioids, and 6% with other adjuvant medications.

A substantial proportion of patients achieved pain reduction with adjuvant pain medications, and the proportion of patients who had benefit was higher than those who had to withdraw from studies because of adverse effects. The highest benefit was seen with opioids.

• Whether non-opioids were given in combination with opioids is unclear in this review.
• Controlled and uncontrolled studies were included.
• Many studies were determined to be of low quality.

Numerous limitations in this review make it difficult to evaluate the relative benefits of various approaches evaluated for management of neuropathic pain. Findings do suggest that results with all types of coanalgesics used appear to have benefits that outweigh the prevalence of adverse effects. Findings continue to support the effect and benefits of opioids as a mainstay of pain management for mixed and neuropathic pain.

To provide preliminary prospective evidence of the efficacy of individual agents prescribed for the treatment of breakthrough chemotherapy-induced nausea and vomiting (CINV)

Patients receiving moderately or highly emetogenic chemotherapy received prophylactic antiemetic treatment based on guidelines. If patients experienced breakthrough CINV, their treating oncologist prescribed antiemetics with discretion and the patients were instructed to complete a questionnaire starting at the point in which they took the antiemetic (baseline) and then every 30 minutes for four hours.

• The sample consisted of 96 participants.
• Median age was 58 with a range of 30–86.
• The sample was 45% male and 55% female. Of the patients completing the questionnaire, 26% were male and 74% were female.
• Diagnoses were breast (7%), GI (26%), genitourinary (4%), skin (4%), lung (13%), gynecologic (23%), head and neck (4%), neuroendocrine (1%), sarcoma (3%), and hematologic (15%).
• Patients were receiving  moderately to highly emetogenic chemotherapy.

The study was conducted at a single site at the Mayo Clinic in Minnesota, United States.

All patients were in active treatment.

The study has applications for late effects and survivorship.

This was a prospective, exploratory observation study.

• Patients rated nausea on a scale of 0–10.
• Patients recorded the number of episodes of vomiting and side effects (e.g., agitation, drowsiness [on a scale of 0–10], headache).
• Patients completed nausea and vomiting questionnaires.

Of the total patients enrolled, 28% experienced breakthrough CINV and completed the questionnaire.

The breakthrough medications given were 10-mg oral prochlorperazine (88%) or a 5-HT₃ receptor antagonist (RA) (12%) (specifically, 1 mg granisetron, 8-mg IV ondansetron, 8-mg sublingual ondansetron).

Patients receiving the prochlorperazine experienced a 75% median reduction in nausea after four hours, and vomiting was reduced from 21% to 4%. Of these, 96% reported they would recommend prochlorperazine to other patients (median satisfaction as 8 out of 10).

Patients who received the 5-HT₃ receptor antagonists experienced a 75% median reduction in nausea over the four-hour study period. No vomiting from baseline was reported (satisfaction as 0, 4, and 8 out of 10). The patient who rated satisfaction at 0 recorded complete resolution of nausea by 30 minutes and said would recommend the medication to others, so investigators posited that this patient may have misunderstood the high satisfaction score of 0 rather than 10.

In the patients treated with prochlorperazine, the median drowsiness of 3 at baseline decreased to 2 after four hours. Headache was reported in 20% of patients and decreased to 0% after four hours. Agitation was reported in 20% of patients and decreased to 4% after four hours. Abdominal cramping, dry mouth, tachycardia, blurry vision were also recorded.

In the patients treated with 5-HT₃ RAs, baseline drowsiness of 5 remained unchanged after four hours. One patient did not have drowsiness at baseline but reported drowsiness of 1 after taking the medication. No patients reported headache, agitation, or other toxicities.

Prochlorperazine and 5-HT₃ RAs appeared to be effective breakthrough antiemetic therapies with favorable outcomes. Prochlorperazine is a good choice base on this study as it acts on a different pathway than prophylactic antiemetics. Further randomized, controlled trials would elucidate more effective antiemetic approaches for treating nausea.

• No appropriate control group was included.
• The analyzable sample size was small.
• The study did not provide a clear control for prophylactic antiemetic regimens.

Prochlorperazine has been used for a long time as a rescue medication. This study supports the choice of antiemetic for breakthrough CINV with minimal side effects. Further randomized controlled trials comparing different side effects are clearly recommended.

To assess the feasibility, safety, and effectiveness of acupressure therapy for preventing or reducing chemotherapy-induced nausea and vomiting (CINV) in children receiving chemotherapy

• Patients were randomized to one of two acupressure treatment groups.
  • In group 1, patients wore acupressure wrist bands during first chemotherapy course, no wrist bands during second chemotherapy course, and placebo wrist bands during the third chemotherapy course.
  • In group 2, patients wore placebo wrist bands during first chemotherapy course, no wrist bands during second chemotherapy course, and true acupressure wrist bands during the third chemotherapy course.
• Patients received standard antiemetic therapy as directed by their physician.
• Patients completed questionnaires before and after each chemotherapy course.

• The study consisted of 18 participants.
• The age range was 5–19 years.
• In group 1, the mean age was 11.7 years (SD ± 4.2). In group 2, the mean age was 12.5 years (SD ±3.6).
• The sample was 50% female and 50% male.
• Cancer diagnoses were acute lymphoblastic leukemia, rhabdomyosarcoma, Ewing sarcoma, medulloblastoma, osteosarcoma, and other diagnoses (not specified).
• The majority of patients (n = 14) were Caucasian, 8 were enrolled in their first chemotherapy course, and 10 were enrolled in their second or later chemotherapy course.
• No patient had used acupressure or acupuncture prior to the study.

The study was conducted in a single inpatient site at a children’s hospital in North Carolina.

All participants were pediatric patients in active treatment.

This was a pilot study. It was a prospective, randomized, crossover clinical trial.

The study used modified methods of Morrow questionnaires. It did not state how the tool was modified. No reliability or validity information was provided.

Questionnaires quantified nausea on an 11-point Likert scale, collected demographics and diagnoses, and measured the following.

• Previous knowledge and experience with acupressure or acupuncture
• Expectations of nausea prevention
• Episodes of emesis
• Presence and degree of nausea
• Side effects
• Satisfaction
• Perceived differences between the acupressure and placebo bands

• Patients somewhat expected the bands to prevent nausea and vomiting. The mean rating of acupressure bands was 6.9 out of 10 and of placebo bands was 5.0 out of 10.
• No difference was found in nausea or number of vomiting episodes among the acupressure band, placebo band, and no band.
• After the bands were worn, many patients reported that their expectations of nausea prevention were met (56% if patients using the acupressure band and 67% of patients using the placebo band) or exceeded (33% of patients using the acupressure band and 28% of patients using the placebo band).
• When no bands were worn, 61% of patients expected more nausea.

Although acupressure bands did not show a reduction in nausea or vomiting, patients perceived the bands as moderately effective, planned to use them in the future, and indicated they would recommend them.

• The sample was small.
• The study did not consider other nausea and vomiting therapy such as antiemetic usage.
• Actual adherence to the wristbands was not reported.
• The reliability of questionnaire use with young children is not clear.

The acupressure bands did not demonstrate a significant change in actual incidence of nausea and vomiting; however, this therapy may be helpful in reducing expectations of CINV.

To evaluate the safety and efficacy of antiemetic medication administration via patient-controlled infusion pump

Patients who failed a standard antiemetic regimen (including a scheduled 5HT3 and one or more additional breakthrough medication of a different class) were placed on a patient-controlled pump containing diphenhydramine 4 mg/ml, lorazepam 0.16 mg/ml, and dexamethasone 0.27 mg/ml mixed in 30 ml of normal saline. The pump ran with a basal rate of 0.1–0.2 ml per hour with a demand dose of 1–2 ml every 30 minutes. The infusion pump was used along with a scheduled 5HT3 agent.

• N = 30  
• MEDIAN AGE = 14.5 years (range = 4–18 years)
• MALES: 47%, FEMALES: 53%
• KEY DISEASE CHARACTERISTICS: Twenty-five patients with solid tumors (sarcoma and neuroblastoma) and five with acute leukemia
• OTHER KEY SAMPLE CHARACTERISTICS: 72% received highly emetogenic chemotherapy and 28% received moderately emetogenic chemotherapy. Dexamethasone was not used in 30% of the cycles for various reasons.

• SITE: Single site    
• SETTING TYPE: Not specified    
• LOCATION: Nashville, TN

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

This was a quasi-experimental trial with no comparison group. Data were from a retrospective chart review of all patients who used an antiemetic pump to control chemotherapy-induced nausea and vomiting (CINV) between March 1999 and April 2004.

Complete response (CR) was defined as no emesis and no rescue medications. If emesis occurred but no rescue medications were used, it was considered a partial response (PR). Failure was defined as the use of rescue medications. Total patient days in CR, PR, and failure were counted for cycles with and without the antiemetic pump. The total number of rescue medications used and the total number of hospital days also were compared.

Patients with an antiemetic infusion pump had more days in CR than without (45 versus 21 days). A larger number of rescue medications were required to control breakthrough nausea and emesis for the conventional prophylaxis versus the antiemetic pump (108 versus 24). Patients with an antiemetic pump had significantly shorter hospital stays.

Using an antiemetic continuous-infusion pump with demand dosing may reduce the total daily dose of each antiemetic medication used individually. Adverse events occurred in 4% of courses, and all side effects resolved with a decreased rate of infusion. No patients required the discontinuation of an infusion pump.

• Small sample (< 100)
• Baseline sample/group differences of import 
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Other limitations/explanation: Retrospective study data; potential for placebo effect of patient-controlled pump

Preliminary data showed that using an antiemetic infusion pump with basal and demand dosing may be an effective way to manage CINV in pediatric patients who fail standard antiemetic therapy. Additional research is needed.

To determine the acceptability and feasibility of HHH-G and the study methods to evaluate its impact on participating men’s skill, self confidence, and self care and to assess the impact of intervention on the participating husbands' ratings of marital quality and depressed mood

HHH-G is a group intervention program with five sessions. Intervention was delivered by two trained educational counselors over five separate 1.5-hour sessions delivered at one week intervals. The five sessions included

• Anchoring yourself to be strong for her
• Listening and not fixing
• Gaining a deeper understanding of her
• Connecting with her
• Putting the pieces together.

Each session included a short group presentation by the education counselors and skill building and efficacy enhancing group exercises. Participants were also provided with spouses' workbooks with session specific activities at home and home assignments that focused on enhancing behavioral capabilities including knowledge and skill. Data were collected at baseline, immediately after the last session, and three months later.

• The sample included 54 couples.
• Couples included women undergoing breast cancer treatment at Princess Margaret Hospital at Toronto and their husbands.
• Mean age of the women was 50.6 years.
• Mean age of the men was 53.1 years.

• Single site
• Inpatient setting      
• Princess Margaret Hospital at Toronto, Canada

Phase of care: active antitumor treatment

A mixed method (one-arm, qualitative, pre-post intervention design) was used.

• Demo/clinical data
• Participation retention and treatment compliance
• Spouse skill checklist
• CASE-S
• CES-D
• Revised Didactic Adjustment Scale (RDAS)
• Mutuality and Interpersonal Sensitivity Scale (MIS)

A moderate to favorable increase in skills was noted as measured by the spouse skill checklist (p < 0.001), including the self care and support subscale (p < 0.001) and the wife support scale (p < 0.003). A significant time effect on self efficacy was measured by CASE-S. No significant changes in depressed mood or marital functioning was noted for the husbands, but a significant reduction in depressed mood (p < 0.003) was noted for the wives.

The feasibility and acceptability of HHH-G were supported. No significant reduction in depression scores were noted for male spouses, which might have been caused by the floor effect because baseline CES-D scores were low in male spouses. A large sample size with a control group woul dneed to be studied to truly examine the effectiveness of this intervention program.

• The study had a small sample size, with fewer than 100 participants.
• There was a risk of bias because there was no control group and no random assignment.
• Findings were not generalizable.

Study demonstrated promising findings on feasibility and reduction in depressed mood for the women with breast cancer. This sounds like a cost-effective approach that could be used by nurses and social workers to improve patient and caregiver outcomes, such as increasing self efficacy and marital functioning.

The interventions included a variety of patient education materials delivered by the following methods.

• General cancer education material (Cancer BACUP, a cancer information and support service for patients in the United Kingdom) specific to the patient's cancer—This material included content about understanding radiation therapy, diet, and cancer-specific information.
• Patient-chosen information selected interactively via computer at the cancer center—The patient was given a choice of six booklets to print from the computer.
• A larger volume of material than in the booklets, not chosen specifically by the patient—This information included 40–47 sections of information.
• Patient-chosen personalized information selected interactively from topics based on the patient’s medical record—These topics included “problem list, treatment lists, or your cancer.”
• A subgroup of participants received anxiety management advice. This information was provided through written materials with self-help advice based on work in cognitive behavioral therapy for anxiety.

Participants were divided into eight groups (three factors, 2 x 2 x 2).

• Group 1: Interactively selected, personalized information, and anxiety management advice (N = 50, t2 N = 48, t3 N = 40)
• Group 2: Interactively selected, personalized information, and no anxiety management advice (N = 50, t2 N = 48, t3 N = 44)
• Group 3: Interactively selected, general information, and anxiety management advice (N = 49, t2 N = 44, t3 N = 35)
• Group 4: Interactively selected, general information, and no anxiety management advice (N = 50, t2 N = 50, t3 N = 49)
• Group 5: Automatically selected, personalized information, and anxiety management advice (N = 50, t2 N = 47, t3 N = 39)
• Group 6: Automatically selected, personalized information, and no anxiety management advice (N = 51, t2 N = 50, t3 N = 44)
• Group 7: Automatically selected, general information, and anxiety management advice (N = 50, t2 N = 49, t3 N = 40)
• Group 8: Automatically selected, general information, and no anxiety management advice (N = 50, t2 N = 48, t3 N = 38)

Measurements were taken at baseline, after intervention, and at three months follow-up.

• Study participants were patients starting radiation therapy.
• A total of 874 patients with cancer were identified through radiation clinic appointments. Of these, 604 patients were recruited to the study, and 270 were excluded.
• Patients were excluded if they were receiving palliative care, had severe symptoms causing distress, had cancer at other sites, did not have English-language skills, were receiving treatment for psychological or psychiatric problems, or were visually or mentally impaired.
• The study reported on a sample of 400 patients with cancer diagnosed from 5 weeks to six years before recruitment.
• Patients completed a questionnaire at home about their previous computer use, information preferences, coping styles, and HSSQ and HADS tests.
• Two-thirds of the patients had breast cancer, and roughly one-third had prostate cancer.
• A total of 348 patients finished follow-up.

Western Scotland

A longitudinal, randomized trial design was used.

• Helgeson’s Social Support Questionnaire (HSSQ)
• Hospital Anxiety and Depression Scale (HADS)
• Questions about the patients’ use and opinions of the booklets and their reported understanding of cancer

At three months follow-up, 45% of patients had improved anxiety scores. There were no statistically significant differences among the three intervention factors using a general linear model.

• The authors concluded that the single information intervention with anxiety management advice in this study did not significantly reduce levels of anxiety.
• This large study showed that brief written anxiety advice does not significantly reduce anxiety in patients with cancer who are starting radiation therapy.

To compare mindfulness-based stress reduction (MBSR) with psychoeducation/support groups (PES) as interventions to treat cancer-related fatigue (CFR) and associated symptoms of anxiety, depression, vitality, sleep disturbances, and pain. An active treatment control group (PES) was used to determine the effect size of MBSR in reducing CRF.

Breast cancer survivors (BCSs) and colorectal cancer survivors (CRCSs) were blinded and randomized into the MBSR group or the PES intervention. The primary outcome was CRF interference, and secondary outcomes of CRF were severity, vitality, anxiety, depression, sleep disturbances, and pain at baseline (T1), postintervention (T2) and at six months postintervention (T3). Both arms of the study included a structured curriculum that lasted two hours weekly for eight weeks. As the MBSR cohort had required exercises and practice assigned between classes, the PES arm was also given between-session practice and supplemental readings related to class topics. Treatment fidelity to each of the interventions was maintained by use of standardized manuals for each (MBSR and PES), audio recordings of the sessions with review by investigators using checklists created to evaluate the interventions. The MBSR intervention was adapted from standard approaches to eliminate the use of a retreat, the addition of psychoeducation, a brief body scan at bedtime, and shorter home practices. The PES program incorporated group discussions.

• N = 69   
• MEAN AGE = BCS: 56.9 years (SD = 9.9 years), CRCS: 56.4 years (12.7 years)
• MALES: 9.9%, FEMALES: 90.1%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Adults aged 18 years or older with nonmetastatic (stage 0–III) BCSs or CRCSs who reported CRF as 4 or greater on the Fatigue Symptom Inventory (FSI)
• OTHER KEY SAMPLE CHARACTERISTICS: Participants had completed active treatment an average of 2.4 years prior to the study and were predominantly Caucasian (70.4%). Forty-six percent of the BCSs were on endocrine therapy at the time of the study, and the only statistically significant difference between groups at baseline was income (p = 0.07).

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: National Cancer Institute–designated comprehensive cancer center clinics

PHASE OF CARE: Late effects and survivorship

Single-blind, two-armed, randomized clinical pilot trail

• FSI
• SF-36 Vitality Scale
• Patient Health Questionnaire-8 (PHQ-8)
• Generalized Anxiety Disorder-7 scale
• Patient Health Questionnaire-9 (PHQ-9) for depression 
• Insomnia Severity Index
• PEG three-item abbreviated version of the Brief Pain Inventory (BPI)
• Global Improvement in Fatigue measure was a single item asking participants to rate their CRF compared to the beginning of the study.

The primary outcome of CRF interference did not significantly differ between MBSR and PES, although a trend (insignificant) toward MBSR was observed at T2 (d = –0.46, p = 0.073). Secondary outcome of vitality demonstrated moderate and significant effect size in the MBSR arm compared to the PES arm (d = 0.53, p = 0.003) at T2; however, the between group difference did not last through the T3 measurement. The MBSR maintained improvement in vitality, whereas vitality improved in the PES group. In addition, at T2, the MBSR participants were significantly more likely to report CRF global improvement (58.8 versus 34.3%, respectively, X² (1) = 4.176, p = 0.041). Both groups continued to report similar global improvements in CRF at T3 (MBSR = 45.5 versus PES = 54.3%, X² (1) = 0.53, p = 0.467). Pain was the only between group secondary outcome in which MBSR demonstrated moderate and significant improvement at T3 compared to PES (d = –0.50, p = 0.014).

Within group effects: Both MBSR and PES participants demonstrated moderate to large effects and significant improvements on all fatigue outcomes at T2 and T3 compared to T1. Participants in both groups also reported moderate to large effects and significant improvements at T2 and T3 from baseline in depression (p < 0.001), anxiety (p < 0.001), and sleep disturbance (p < 0.001).

Although the aim of this study was to rigorously test MBSR as an intervention for CRF in preparation for a phase-III randomized, controlled trial, the study supported the strength of PES as an intervention as well.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (sample characteristics)
• Findings not generalizable

Although MBSR has been shown an effective intervention for numerous cancer-related symptoms, including CRF, a structured PES intervention was also clearly effective in helping survivors manage fatigue and other symptoms. However, given the more immediate effect of MBSR for participants, MBSR may provide results sooner. Both interventions are efficacious and therefore provide cancer survivors a choice in interventions effective in reducing CRF and its interference in daily life through anxiety, depression, and sleep disturbance.

To examine the effect of an eight-week Mindfulness-Based Stress Reduction (MBSR) program compared to an eight-week education and support (ES) program on subjectively and objectively assessed cognitive function among breast and colorectal survivors experiencing fatigue

• N = 69  
• AGE = 56.9 years
• MALES: 9.9%, FEMALES: 90.1%
• KEY DISEASE CHARACTERISTICS: Causasian (70.4%), not college educated (56.3%), employed (52.1%), married or partnered (54.9%), self-reported “comfortable income level” (52.1%)
• OTHER KEY SAMPLE CHARACTERISTICS: Cancer type: Breast (MBSR 51.7%), (ES 48.3%), CRC MBSR (36.4%), (ES 63.6%). Average years since treatment completed was 2.4 years. Any individual reporting experience with meditation was excluded from the sample. Over 50% did not have more than a high school education.

• SITE: Single site  
• SETTING TYPE: Multiple settings  
• LOCATION: Midwestern National Cancer Institute–designated cancer center and affiliate clinics

PHASE OF CARE: Late effects and survivorship

Two-arm, randomized, clinical trial, pilot study

This pilot study demonstrated that MBSR offers significant and sustained improvements in both subjectively and objectively measured chemotherapy-related cognitive impairment. The findings indicated that the MBSR intervention addressed issues of executive function and attentional control in breast and colorectal survivors reporting cancer-related fatigue and cognitive impairment.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• Findings not generalizable
• Fatigue levels were used as a proxy for the presence of chemotherapy-related cognitive impairment in the selection of sample. The presence of chemotherapy-related cognitive impairment was assessed at baseline after selection of the study sample, and, at that time, a \"large majority of participants reported cognitive impairment as measured by the baseline AFI.\"

The findings of this study suggest that MBSR may improve late effect cognitive/emotional fatigue and cognitive impairment in patients with cancer. As no identified adverse effects of MBSR training or mindfulness meditation exist, this low-risk intervention may be beneficial for patients.

To evaluate the safety, tolerability, and efficacy of linaclotide in patients with chronic constipation.

Patients recorded data related to daily bowel habits and called into a voice response system daily to record their medications taken and bowel movements. Patients were randomized to receive 100, 300, or 1,000 mcg of linaclotide or placebo once daily in the morning, in the fasting state.

• The study reported on a sample of 36 patients.
• Mean patient age was 45.2 years (SD = 12.17).
• The sample comprised 88% women and 12% men.
• Diagnosis-specific information was not provided.
• Patients were excluded if they had pelvic floor dysfunction.
• All patients had experienced constipation for 12 or more weeks within the past year.

• Multi-site
• Outpatient
• United States

This was a randomized, double-blind, placebo-controlled, parallel group, phase IIA study.

• Bristol Stool Form Scale
• Ease of Passage Scale
• Subjective patient-reported outcomes of discomfort and overall relief on seven-point Likert-type scales
• National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0

• All doses of linaclotide produced a three-fold greater increase in number of spontaneous bowel movements compared to placebo (p = 0.047).
• Weekly stool frequency increased in a dose-related manner.
• Stool consistency improved in all dose groups in a dose-related manner compared to placebo (p < 0.01).
• Patient-reported outcomes improved with all doses of linaclotide, but were not statistically different than those seen with placebo.
• No severe adverse events were reported. The most common adverse event was diarrhea.

Linaclotide appeared to improve symptoms of chronic constipation and was well-tolerated overall.

• The sample size was small (fewer than 100).
• The study was likely underpowered.

The usefulness of linaclotide for patients with cancer who have constipation is not yet known. This medication is a peptide that binds to specific receptors on the membrane of intestinal enterocytes and may increase efflux into the intestinal lumen with concomitant fluid secretion. Those effects may improve stool consistency and transit time. Nurses should be aware that a variety of new medications aimed at management of constipation with various mechanisms of action are being developed. Applicability to patients with cancer has not yet been studied.

This small pilot study had two objectives:  (1) to design a strategy for recruitment tailored to the institutional environment and therapeutic intervention and (2) to collect evidence of preliminary effects.

In a two-part intervention, patients were first taught to improve self-care with regard to exercise, nutrition, and cognitive-behavioral techniques over a four-week period. They were then provided with eight weekly 50-minute acupuncture sessions. This therapeutic protocol references a conceptual framework derived from two theories—Social Cognitive Theory and Integrative Medicine Theory—but did not provide a description of the theory to match the interventions (exercise, nutrition, cognitive therapy, or acupuncture) with conceptual variables in the model.

• The sample was comprised of 13 women with breast cancer.   
• Mean age was 54 years (range 18–65). 
• About two-thirds of the patients were white.

• Single site  
• University of California Los Angeles Center for East-West Medicine
   

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for late effects and survivorship.

This was a randomized, controlled feasibility study.

• Brief Fatigue Inventory (BFI) to assess cancer-related fatigue (self-reported)
• Functional Assessment of Cancer Therapy–Cognitive Function, version 2 (FACT-COGv2) to measure three dimensions of perceived cognitive impairment:  cognitive problems, impact on functioning, and impact on health-related quality of life (self-assessment without objective measures)

Failure of the recruitment methods led to the development of a tailored recruitment strategy. The intervention was said to be associated with a 2.38-point decline in fatigue (BFI) (90% confidence interval [0.586, 5.014]; p < 0.10). Differences in perceived cognitive dysfunction outcomes were not statistically significant between the two groups over time. The authors talked about using a pooled standard deviation for the BFI at baseline to compare the means of the two groups to determine the effect size.

An effective recruitment strategy is necessary for the execution of any randomized, controlled trial. The conceptual framework integrating social cognitive theory and integrative medicine was not effectively operationalized.

• The pooled standard deviation was not reported. It was unclear how the Cohen’s D metric was applied to this small study.
• The study had a small sample size, with less than 30 patients; 13 patients were randomized of 40 recruited.
• The study had a poor design.
• Numerous confounding variables were not controlled for in the first part of the intervention in which patients were taught to improve self-care by optimizing exercise routines, improving nutrition, and implementing various cognitive-behavioral techniques.
• The tailored recruitment strategy of two two-hour recruitment sessions is labor intensive to yield only 5 interested patients.
• One patient assigned to the control group actually received acupuncture and patient education, but his/her results were calculated with the control group.
• The study was nonblinded.

Investigation into outcomes attributed to specific patient education interventions might first be warranted before blending such an educational intervention with a complimentary/alternative therapy studying efficacy on cancer-related fatigue.