To draft an algorithm for optimal management of cutaneous adverse events with epidermal growth factor receptor (EGFR)-inhibitors in patients receiving EGFR treatment.

The quality of publications was analyzed using the Oxford scale for methodology. Information about practices was collected through a questionnaire developed by a steering committee. The questionnaire was completed by 67 individuals including oncologists, gastroenterologists, and radiotherapists via regional meetings in seven towns in France, chaired by three to five local experts. A national meeting was held to build an algorithm. Participants comprised 20 members who were on the steering committee, were regional meeting chairs, and were in a bibliographic study group.

Databases searched were PubMed, Embase, and the Cochrane Collaboration. Reference lists of articles retrieved were manually searched.

Search keywords were EGFR inhibitor (and each specific drug name), skin toxicity, rash, acne, aceneiform, nail, paronychia, hair, alopecia, hirsutism, hypertrichosis, trichomegaly, xerosis, pruritus, and itch.

Inclusion and exclusion criteria were not stated.

• Recommendations regarding the use of preventive doxycycline on initiation of EGFR are level II. All other recommendations are level IV, expert opinion only.
• Preventive measures on introduction of EGFR inhibitors include the following.
  • Systemic cyclines (doxycycline 100–200 mg per day, lymecycline 300 mg, or minocycline 100 mg) for at least six weeks
  • Moisturizing skin cream
  • Perfume-free cleanser with pH close to skin pH
  • Conventional photoprotection with clothing or an anti-ultraviolet with a sun protector factor (SPF) of 15 or higher
  • Cut nails straight, but not too short.
  • Nonaggressive shaving, with caution
  • Avoid harsh manicure or pedicure, ordinary soap, alcohol-based products, and physical irritation.
• Provide care for folliculitis according to grade and paronychia according to the level of symptoms. Use the same types of interventions as outlined for prevention, with the addition of topical steroids in paronychia.
• Additional recommendations with xerosis by grade are provided, including use of emollients (e.g., bath oil), occlusive dressing, and skin adhesive with fissures.
• Topical steroids are not indicated for xerosis, and the efficacy of antihistamines has not been demonstrated.

• Most recommendations had expert opinion–level evidence only, and comprised general skin and nail care recommendations.
• The investigators noted that few data exist regarding dose reduction with EGFRs to evaluate the impact on skin lesions.

This algorithm recommended prophylactic use of systemic cyclines with EGFR treatment across the board. Additional skin and nail care recommendations provided generally are seen elsewhere and are in agreement with expert consensus. A lack of clarity exists regarding dose reduction or treatment delays and the impact on skin symptoms. In addition, a lack of research evidence exists for interventions other than cyclines.

STUDY PURPOSE: To explore the efficacy of interventions provided to couples 

• FINAL NUMBER STUDIES INCLUDED = 23
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Not provided
• KEY SAMPLE CHARACTERISTICS: Various tumor sites; more than 80% of patients and caregivers were Caucasian; 86% of caregivers were spouses; more than 62% of patients and caregivers had at least some college education.

Six studies evaluated social adjustment for patients and partners. All showed greater improvement in adjustment for intervention partners at various study time points. Nine studies evaluated relationship functioning and the quality of the patient-partner relationship. All of these showed improvement with the intervention at various time points in the study. Five studies evaluated coping strategies, and all showed greater improvement in coping with the intervention. Of four studies that looked at self-efficacy, two showed improvement with the intervention and two showed no significant effect. Two studies assessed partner communication, and both showed improvement with the intervention. Interventions in early-stage cancer appeared to result in greater improvement compared to those targeting late- or advanced-stage cancer. No significant differences were found comparing face-to-face and telephone delivery of interventions. In eight of the studies, the interventions were provided by nurses. Other providers were social workers, psychologists and therapists, or counselors (no experience or qualifications provided).

Couple-based psychosocial and psychoeducational interventions are shown to be effective in improving caregiver coping and self-efficacy, as well as couple relationship and communications. Face-to-face and telephonic delivery of the interventions were effective.

Samples were all well-educated Caucasian individuals in heterosexual relationships, so these findings may not be applicable to other groups.

Findings show clear benefits of psychoeducational types of interventions delivered to couples for caregivers and patients, and that these have been effectively provided by nurses. Findings also suggest that delivery in formats other than face-to-face situations can be beneficial. Additional research in the efficacy of various modes of delivery would be useful, so that clinicians can determine the most cost-effective and practical approaches that are helpful to patients and caregivers.

To determine indications, results, and predictors of successful opioid rotation

Records of consecutive patients who received strong opioids and had follow-up data within six weeks of the initial clinic visit were reviewed and analyzed.

• N = 146 patients with six weeks of data; 114 had opioid rotation
• MEDIAN AGE = 55 years
• MALES: 60%, FEMALES: 40%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types
• OTHER KEY SAMPLE CHARACTERISTICS: 71% Caucasian, 12% African American, 11 % Hispanic

• SITE: Single site 
• SETTING TYPE: Outpatient 
• LOCATION: Texas

• APPLICATIONS: Palliative care

• Retrospective, descriptive

• Edmonton Symptom Assessment Scale
• Symptom Distress Scale
• Delirium Assessment Scale
• Cut down, annoyed, guilty, eye-opener (CAGE) questionnaire

Successful opioid rotation was defined as improvement in side effects if that was the reason for opioid rotation, or a 30% or 2-point reduction in pain if uncontrolled pain was the reason for opioid rotation. For 95% of patients, uncontrolled pain was the reason for opioid rotation. Sixty-five percent of patients had successful opioid rotation.  No difference was seen in success based on ethnic and demographic data. Scores for pain (p < .001), insomnia (p = .013), and depression (p = .04) were improved at follow-up, with no significant difference in morphine equivalents at follow-up.

Findings suggest that opioid rotation is successful in some patients for improvement in pain management.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Opioid rotation has been suggested in cases of uncontrolled pain for individuals on strong opioids, but little research has been done in this area. This study is purely descriptive, but does suggest that opioid rotation can be successful to improve pain control for some patients.

To evaluate the impact of bright white light exposure on fatigue among cancer survivors

Patients were randomized to receive bright white light or dim red light treatment, using a lightbook device that used light-emitting diode (LED) light. Participants were instructed to self-administer the treatment at home by placing the light box at a 45-degree angle, 18 inches from the face, for 30 minutes every morning for four weeks. Study questionnaires were completed at baseline, after two weeks, at four weeks, and three weeks after study completion.

• N = 36  
• MALES: 19%, FEMALES: 81%
• KEY DISEASE CHARACTERISTICS: Patients with multiple types of cancer. Initial curative treatment had been completed. Patients were an average of 17 months post diagnosis.

• SITE: Single site  
• SETTING TYPE: Home    
• LOCATION: New York

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale

Fatigue declined in all over time. At all study time points, the white light group had less fatigue (p = 0.00125). The pattern of change in fatigue also differed between groups. In the red light group, fatigue improved at two weeks but became worse at four weeks and at follow-up. At the end of four weeks, no patients in the bright white light condition were still clinically fatigued.

Daily exposure to bright white light was associated with a significant reduction in fatigue.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• No information is provided about any other interventions received for fatigue during the study.

The findings suggest that exposure to bright white light can be an effective alternative in managing fatigue. This is a relatively low-cost and low-risk intervention that may be helpful. Further research in this area is warranted.

• Databases searched were National Library of Medicine PubMed database, which includes MEDLINE, PreMedline, and other related databases (1979-January, 2000).
• Search keywords were cancer and behavior, intervention, nausea, vomit, depression, anxiety, fatigue, neuro, cognitive, menopause, sex, and post-traumatic stress disorder.
• Studies were included if they were randomized controlled studies, within-subject studies, or case reports.

• The review consisted of 54 studies that met the criteria.
• Three symptom clusters were evaluated. The review included published reports for nausea and vomiting, anxiety/stress, and pain.
• For the nausea and vomiting review, studies must have addressed
  • Cancer-related treatment side effect with behavioral intervention
  • Cancer-treatment intervention effects.

• The following treatments were evaluated: relaxation, hypnosis, cognitive/attentional distraction, desensitization, and rehearsal modeling.
• Four studies for relaxation and hypnosis showed effectiveness of behavioral intervention for control of anticipatory nausea and vomiting (no anticipatory vomiting occurred).
• Results from the individual analyses were confirmed in 12 of 13 randomized-controlled trials that compared behavioral interventions with no treatment/attention control conditions.
• The impact of behavioral intervention on postchemotherapy side effects was less established, with four studies reporting that the behavioral intervention reduced the intensity of the postchemotherapy side effects but did not prevent their occurrence.

To help patients manage fatigue, as well as optimize activity and functioning, through energy conservation and management.

The intervention was comprised of four principle components:

• Detailed assessment of fatigue
• Provision of an educational pack on fatigue management
• Monthly meetings to facilitate the provision of advice and coaching on fatigue management strategies
• Exploration of the meaning of fatigue for patients in their daily lives.

The intervention was provided over the first three treatment cycles.

• In total, 103 (55% male) chemotherapy-naïve patients diagnosed with non-Hodgkin lymphoma or gastrointestinal, non-small cell lung, colorectal, breast, or unknown primary cancer were included.
• Mean age was 56.5 years.
• The disease group was most commonly esophageal (22%), and the disease status was most commonly locoregional disease (45%).
• Patients were excluded if they were being treated for psychiatric illness.

• Multisite
• Inpatient and outpatient
• Clinics at two regional cancer centers in the United Kingdom

Patients were undergoing the active treatment phase of care.

The study was a randomized, two-arm (standard versus experimental treatment), unblinded, controlled trial.

• Visual analog scales (VASs):  subjective quantification of fatigue, subjective distress because of fatigue, and subjective assessment of fatigue effects on chores/work and pastimes/hobbies
• Fatigue diary
• Short Form 36 Health Survey (SF-36)

The experimental group experienced a 20% pre-/posttest decrease in the different dimensions of fatigue, whereas a negligible difference was observed for the control group. Across all measures of fatigue (VASs and the vitality subscale of the SF-36), the experimental group reported less fatigue by the end of the study than the control. The intervention was particularly successful in decreasing distress evoked by fatigue (p < 0.01) and reducing the impact of fatigue on favored pastimes (p < 0.02). Analysis of the mean fatigue score revealed a significant between-group difference in global fatigue (p < 0.03).

• Patients were at liberty to receive fatigue management information and support from outside sources.
• The study was unblinded; therefore, it was possible that patients in the treatment group experienced a placebo effect and that investigator bias may have impacted the results.
• Cost data were not collected; therefore, it was not possible to assess the cost-effectiveness of the intervention.

To report on using a fatigue intervention adapted for telephone use and the findings of an exploratory controlled trial

The Beating Fatigue intervention was delivered over the first three treatment cycles to patients starting chemotherapy. The intervention included fatigue education, fatigue assessment, self-care coaching, and emotional support. Participants were given an information packet, a fatigue diary, and a support nurse consultation with each treatment cycle. The modified version included a telephone consultation and motivation interviewing. The control group received usual care consisting of inquiring about fatigue levels. Phase 1 work was done to establish acceptability. In phase 2, patients were randomly assigned to intervention and control groups.

• N = 44  
• MEAN AGE = 53.3 years
• MALES: 39%, FEMALES: 61%
• KEY DISEASE CHARACTERISTICS: 59% breast, 32% lymphoma, and 9% colorectal
• OTHER KEY SAMPLE CHARACTERISTICS: 68% white British

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: Large cancer center in the United Kingdom

• PHASE OF CARE: Active antitumor treatment

Mixed-method exploratory study; phase 1 to explore feasibility and acceptability of telephone-delivered version of intervention; phase 2 to measure treatment effect, patient acceptance, and treatment integrity

• Brief Fatigue Inventory (BFI)
• Fatigue Distress Scale (FDS)
• Hospital Anxiety and Distress Scale (HADS)
• Fatigue Self-Efficacy (FSE) scale 
• Semi-structured interviews
• There was no description of the instruments in the article, including measurement performance (e.g., reliability). Consequently, the full evaluation of the findings are not possible without information regarding instruments not commonly used in research (e.g., FDS, FSE).

Fatigue intensity decreased in the intervention group and increased in the control group (effect size [ES] = 0.18). Distress and anxiety decreased in the intervention group and increased in the control group (ES = 0.62, ES = 0.31, p = 0.05), and self-efficacy increased in the intervention group and decreased in the control group (ES = -0.34, p = 0.05). Depression increased in both groups slightly.

Fatigue improvement was small based on the effect size. Interviews suggested the acceptance of telephone interventions by patients. Distress from fatigue was decreased for participants. The results of this study showed improvement in self-efficacy and anxiety with the intervention.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)

This nurse-delivered intervention may improve patient distress associated with fatigue and reduce fatigue severity. Motivational interviewing might be helpful in managing anxiety. Additional research to develop this evidence is needed.

An energy-dense oral nutritional supplement of eicosapentaenoic acid (EPA-ONS), an anti-inflammatory agent, was shown to reduce weight loss, increase lean body mass, and improve functional capacity and nutritional status in previous research. The EPA intervention instructed patients to consume two tetrapaks (480 mL) of EPA-ONS per day in addition to their regular diet for a total of nine weeks. Tetrapacks contained 16 g of protein, 1.09 g of EPA, and 0.46 g of docosahexaenoic acid (DHA). Chemotherapy commenced at week 4 and was repeated every two weeks. Patient outcomes were assessed at baseline, the end of week 3, and the end of week 9.

• The study was comprised of 23 patients with advanced colorectal cancer (CRC) who had one prior chemotherapy regimen (median age = 61 years).
• The majority of the patients was male (n = 15) and had received previous surgery and chemotherapy (n = 17). 
• Patients were excluded if they had previously received irinotecan, had preexisting intestinal disease, psychiatric disorders, edema, dehydration, or were unable to orally intake medications. Patients who could not have a three-week delay in administering cytotoxic chemotherapy without impacting disease progression were also excluded.

The study was conducted at the Royal Prince Alfred and Concord Hospitals in Sydney, Australia.

Patients were undergoing the active treatment phase of care.

This was an open-label, phase II study.

Disease and treatment assessment (DATA) form

The EPA intervention resulted in a trend toward improvement during the full course of therapy for overall well-being (p = 0.05) and energy (p = 0.03). The quality of life measure for fatigue was maintained at the same mean score throughout the study.

• The study had a small sample size.
• The study lacked a neutral comparison group.

To determine, by means of a meta-analysis and systematic review, the effectiveness of treatment with antidepressants in people with depression in the context of physical illness

• The Cochrane Register of Clinical Trials, MEDLINE,^® EMBASE, PsycINFO, ClinicalTrials.gov, Current Controlled Trials Register, LILACS, CINAHL,^® PSYNEX, AMED, and the pharmaceutical industry trials registers of GlaxoSmithKline and Eli Lilly were consulted.
• The following inclusion criteria were used: any type of antidepressant used; patients older than 18 years, with depression in the context of a physical illness; and depression defined as diagnosis of major depressive disorder, adjustment disorder, or dysthymic disorder, according to DMS-IV or ICD-10 or scores indicative of a diagnosis on validated tools. The main comorbidity was a physical health problem with a biological underpinning, not just symptoms. The control condition was a placebo.
• The study was excluded if patients had psychiatric comorbidity or if the study involved trials in which antidepressants were prescribed to treat symptoms other than those of depression.
   

• A total of 2,230 references were retrieved.
• Risk of bias was evaluated with Cochrane handbook criteria.
   

• 51 studies were included.
• Studies included patients with stroke, AIDS, Parkinson disease, cancer, chronic obstructive pulmonary disease, diabetes, myocardial infarction, renal failure, heart failure, epilepsy, and chronic prostatitis. Age range was 33–82.
• Four of the trials involved patients with cancer, mostly women with breast cancer. In those trials, the age range of the 254 patients was 35–91.
   

Most of the studies involved use of tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs); three studies looked at mirtazapine. In 25 studies providing data on short-term response, odds of response were greater with antidepressants (OR = 2.33, 95% CI, 1.8–3.0, p < 0.00001). Across 20 studies (N = 1,214 patients), at six to eight weeks antidepressants were more effective than placebo in reducing symptoms of depression (SMD = 0.66, 95% CI, –0.94 to –0.38, p < 0.00001). Analysis of medium-term response at 9–18 weeks showed odds of response were greater with antidepressant drugs than placebo (OR = 2.08, 95% CI, 1.33–3.24, p = 0.00001). Long-term response ( > 18 weeks) was better with antidepressants than placebo (OR = 2.13, 95% CI, 1.31–3.47, p = 0.002). Heterogeneity had a low impact on the meta-analysis reported. In the short term, fewer patients receiving placebo dropped out of the study. Most frequent adverse events were dizziness, dry mouth, headache, nausea, constipation, insomnia, sexual dysfunction, sedation, hypotension, and appetite change. No trials studied patients with advanced cancer,

Antidepressants were superior to placebo for treatment of depression in people with a physical illness.

The large number of studies were of relatively low quality, which may have inflated the effect sizes calculated. Depression was presumed to be similar across physical diseases. No subgroup analysis was conducted for different diseases.

Findings showed that treatment with antidepressants is superior to use of placebo in patients with physical illnesses who have moderate or major depressive disorders in the context of the physical illness. Antidepressants may benefit patients with cancer who have moderate to major depression. Applicability of antidepressants for patients with advanced cancer is unknown. Nurses should be aware of the side effects of antidepressants and how they may contribute to various disease or treatment symptoms.