To explore the interdependence of changes in oxygen uptake, quality of life (QOL), and cancer-related fatigue (CRF) during a four-month exercise intervention

Aerobic exercise capacity was determined by a physician-supervised cardiopulmonary exercise test on an electrically braked cycle ergometer. An initial watt load of 0 watts was increased by 25 watts every three minutes until exhaustion. The results were used at an initial exercise counseling session to individualize exercise plans (i.e., frequency of three to five times per week, intensity, type of exercise, opportunity to participate in a Nordic walking training session once per week). Subjects attended a second counseling session four weeks into the intervention to adjust home-based exercises to fit their conditions. An exercise counselor was available by phone, via email, or in person at any time during the intervention. Assessments were repeated at the end of 16–20 weeks. Self-reported measures of adherence to exercise plans were obtained by diaries.

• N = 101  
• AGE RANGE = 32–85 years
• MALES: 40%, FEMALES: 60%
• KEY DISEASE CHARACTERISTICS: Confirmed cancer diagnosis (any site and stage) within the past three years; during adjuvant, palliative, or postadjuvant therapy (finished within the past 12 months); performance status of 0–II (as ranked by the Eastern Cooperative Oncology Group); exclusion criteria included brain or bone metastasis, uncontrolled hypertension, hemoglobin counts < 8 g/dl, and any condition precluding exercise

• SITE: Multi-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Germany

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care 

Repeated measures pre- and postintervention

• Aerobic exercise capacity measured by a cardiopulmonary exercise test (CPET) and the peak oxygen consumption (VO2PEAK) 
• QOL measured by the European Organisation for Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 v.3.0)

Subjects were active (i.e., hiking, biking, walking, bicycling) three to six times per week for 60–300 minutes at 60%–100% of individual anaerobic thresholds. At baseline, the groups differed in QOL scores but not CRF or VO2PEAK scores. Subjects with complete data sets had a significant increase in VO2PEAK and QOL scores, and their fatigue decreased significantly over the course of the intervention. No significant effect for diagnosis or time since diagnoses occurred.

A relationship between exercise capacity enhancement, QOL improvement, and fatigue symptom reduction exists during and shortly after cancer treatment.

• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Findings not generalizable
• Questionable protocol fidelity

The data in this study support the role of individualized exercise planning based on baseline exercise capacity with respect to frequency, time, and intensity as well as the importance of patient choice in the type of exercise in which to participate.

To determine the comparative efficacy and safety of gabapentin and amitriptyline as coanalgesics for cancer-related pain

Patients were assigned randomly to receive oral tramadol 150–200 mg and oral gabapentin titrated from 600–1,800 mg daily, or tramadol 150–200 mg and amitriptyline titrated from 25–100 mg daily. Oral morphine or fentanyl transdermal patch were used as rescue medication. At baseline, if patients were on any coanalgesic, they were entered after a washout period. Patients were followed monthly up to six months. Patients were asked to maintain a diary used for assessment of compliance. Once a patient used rescue medication, the patient was excluded from further efficacy assessment, and last pain scores were carried forward.

• N = 76  
• MALES: 53%, FEMALES: 47%
• KEY DISEASE CHARACTERISTICS: Tumor types are not stated. Baseline pain scores were 8.425 on average.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients did not have any disorder of vital organs or bone marrow.

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

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care

• Open-label, two-group, randomized trial

• Visual analog scale (VAS)—scored as 0, 1, or 2 if scores decreased, remained the same, or increased
• Verbal rating scale (VRS)
• Percentage of pain relief (PPR) calculated
• Global pain score calculated as the sum of changes in VAS score, VRS score, and PPR
• MD global impression of efficacy (four-point scale)

For patients receiving gabapentin, pain scores on the VAS reduced significantly between the first and second month (p < .001). The same timing and pattern of pain reduction were shown in the amitriptyline group (p < .001). No significant differences were seen between groups at any study time point. Six patients on gabapentin and eight patients receiving amitriptyline required rescue medication. Thirty percent of patients in the gabapentin group and 42% of patients in the amitriptyline group had adverse events. These were generally mild. More patients receiving amitriptyline experienced postural hypotension (p = .02) and dry mouth (p = .04). Sedation, dizziness, and dyspepsia were the most frequent side effects.

Findings suggest that gabapentin and amitriptyline can be effective as coanalgesics for neuropathic pain.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Findings not generalizable
• Subject withdrawals 10% or more
• Other limitations/explanation: Information regarding any changes in opioid medications or lack of change is not provided. No data regarding compliance are provided. Depending on the timing in which patients who used rescue medication had prior pain scores carried forward, this approach could have overestimated or underestimated results. Opioid dosage information is not provided. The sample did not appear to have any significant comorbid conditions, so applicability among patients with other chronic diseases is unclear.

Findings suggest that either gabapentin or amitriptyline can be effective coanalgesics for neuropathic pain, and professional guidelines generally have suggested consideration of such medication. The side effect profiles of the two drugs studied here were slightly different, so individual patient characteristics and risks need to be considered in medication selection. In this study, patients had no significant other disorders, so if similar results would be seen among patients with comorbid conditions is not clear.

The yoga intervention was a 90-minute, six-week course taught by expert yoga trainers. The course included meditative practices, various postures, guided imagery of cancer cells, positive thought provocation, chanting of various sounds according to the respective patient’s religious beliefs, awareness practices, deep relaxation, and soothing sound vibrations. Control group patients were given supportive counseling and advised to take light exercise.

• The study reported on a sample of 68 women with breast cancer receiving radiotherapy and/or chemotherapy.
• Of these, 58 completed the study: 35 in the yoga intervention group, and 23 in the supportive counseling group.

Three centers in India

A randomized controlled trial design was used.

• Hospital Anxiety and Depression Scale (HADS)
• Perceived Stress Scale
• Alkaline single-cell gel electrophoresis (comet) assay to study cellular DNA damage from peripheral blood

There was significant decrease in anxiety levels in the yoga intervention group (repeated measures ANCOVA, p < 0.001). Yoga intervention decreased anxiety in women with breast cancer receiving radiation therapy.

• The study had a small sample size.
• The study used a convenience sample: Patients may self-select to participate in a study they believe to be effective.
• Start of intervention was not linked to time into radiation treatment and/or administration of chemotherapy.
• Expert yoga trainers were required to administer the yoga courses.

To investigate the impact of early integration of palliative and supportive care on pain management

Patients involved in the palliative care group were seen within two to three weeks of the cancer diagnosis. Services provided by the palliative and supportive care team were individualized, but included comprehensive symptom management, psychosocial, spiritual, and emotional support to patients and families, as well as assistance with treatment choice and coping. Patients in the comparison group received standard care provided by primary specialists. Data were collected from medical records. Patients were interviewed by a pharmacist regarding perception of pain control and pain intensity on a verbal rating scale.

• The study reported on a sample of 1,450 patients.
• Mean patient age was 65.05 years.
• The sample was 56% male and 44% female.
• Of the sample, 81% had metastatic disease. Specific sites were not described.
• A significantly larger percentage of patients receiving palliative care were receiving opioids and strong opioids for pain.

• Multisite
• Inpatient setting
• Italy

The study has clinical applicability for palliative care.

A descriptive, two-group comparison design was used.

Verbal rating scale (five-point)

Use of morphine and oxycodone were higher in the palliative care group (p < 0.0001). Transdermal fentanyl was used more often in the usual care group (p < 0.0001). Results from the interview showed that the percentage of patients with no pain and mild pain were significantly higher in the palliative care group (p < 0.0001). Care model and gender were the only predictive variables for pain outcomes, with male patients reporting lower pain severity (p = 0.003). Type of analgesics used was not a significant predictor of pain scoring results.

Findings suggest that provision of early palliative and supportive care is associated with lower pain severity than provision of standard care. There were significant differences in the types of analgesics used between care models, but this factor was not predictive of measured pain severity.

• The study has baseline sample and group differences of import.  
• The study has risk of bias due to no control group, no blinding, no random assignment, and no appropriate attentional control condition.
• Measurement validity and reliability are questionable.
• Pain was measured at only a single time point.
• Duration of palliative care and time since diagnosis for the entire sample are not described.
• There is limited information about content of standard care as well as overall pain management approaches in all patients.

This study design is associated with multiple limitations and threats to validity, so results cannot be seen as conclusive. Findings do suggest that an integrated care delivery model, incorporating holistic palliative and supportive care that is initiated early in the course of cancer care, may be associated with greater control of cancer-related pain.

To evaluate the efficacy and tolerability of low dose morphine in comparison to standard doses of weak opioids in the treatment of moderate cancer pain in opioid naïve patients

This multicenter, 28-day, open-label randomized controlled study for adults with moderate cancer pain assigned to receive either a weak opioid or low dose of morphine was designed to evaluate the efficacy and tolerability of low dose morphine in comparison to standard doses of weak opioids in the treatment of moderate cancer pain in opioid naïve patients. The weak opioid group received either tramadol or codeine with or without paracetamol. The morphine group received morphine after a three-day titration phase with normal release morphine up to 30 mg per day. The groups were assessed every seven days.

• N = 240   
• AGE = 59–74 years (WO group), 56–74 years (M group)
• MEDIAN AGE = 68 years
• MALES: 57% (WO group), 47.5% (M group); FEMALES: 43% (WO group), 52.5% (M group)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Both solid tumors and hematologic tumors
• OTHER KEY SAMPLE CHARACTERISTICS: Pain intensity, cancer symptoms, Karnofsky score, age, mental capacity

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: 17 Italian oncology centers

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care, palliative care 

• Multicenter, 28-day, open-label, randomized controlled study

• Numerical Response Scale (0–10) for pain
• Karnofsky Performance Status Scale, 60% or higher for patient functioning 
• Edmonton Symptom Assessment System (ESAS) used to assess nine symptoms commonly experienced by patients with cancer during the previous 24 hours (validated in the Italian language)

In patients with cancer and moderate pain (4–6 out of 10), low-dose morphine reduced pain intensity significantly compared to weak opioids (tramadol or codeine) with a similarly good tolerability and adverse effects.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Long accrual of patients
• Open-label design

This study is has very important patient and nursing implications. By not using step II, weak opioids, we could potentially have better control of our patient’s pain as well as decrease costs by not using some of the more expensive weak opioids. More research is needed to compare the most commonly used strong opioids as first-line medications for pain intensity and adverse effects. Future studies should prospectively determine the morphine equivalent daily doses. These studies may determine that step II opioids are less effective and more costly. Ending step II in the World Health Organization's (WHO) ladder could simplify pain management while giving better pain control in a more efficient manner.

To compare intracerebroventricular (ICV) opioid therapy with either subarachnoid (SA) or epidural (EPI) opioid therapy

DATABASES: AgeLine (1978–1991), Bioethics (1973–1994), BIOSIS (1969–1991), Catline (through 1991), Dissertation Abstract (1966–1991), EMBASE (1974–1991), ERIC (1966–1991), FEDRIP (1966–1991), GPO (1976–1991), Health (1975–1991), NTIS (1964–1991), Psychological Abstracts (1967–1991), Religion Index (1975–2001), Sociological Abstracts (1963), Social Science Research (1972), MEDLINE (1966–2003), CINAHL (1982–2003), and CANCERLIT (1975–2002)

COMMENTS ON LITERATURE USED: Data were extracted from trials and used to compare analgesic efficacy, pharmacologic adverse effects, and catheter and system problems. No controlled trials were identified for these treatments. Data extracted looked at the best available evidence to evaluate the use of these treatments in patients with cancer.

FINAL NUMBER STUDIES INCLUDED: ICV = 13 trials (337 patients); EPI = 31 trials (1,343 patients); SA = 28 trials (722 patients)

TRIALS EVALUATED: No controlled trials were identified for these treatments.

Uncontrolled studies show that neuraxial opioid therapy often is effective for treating cancer pain that has not been controlled by systemic treatment. Long-term use of neuraxial therapy can be complicated by problems with catheters. Some of the therapies are costly. ICV therapy is more costly; however, comparative efficacy, side effects, and system longevity are unknown.

More rigorous reporting of efficacy and complications needs to be done before ICV can be recommended as a first-line therapy.

To obtain feasibility and effect size data for the intervention of true acupuncture on cancer-related fatigue (CRF) in patients receiving radiation therapy.

Participants were randomized to receive acupuncture or sham acupuncture; there were three real intervention assignments for every two sham assignments. Needles were in place for 30 minutes per session, and participants had treatments once or twice per week during the four to six weeks of the trial. Needle placement for true and sham interventions were specifically described in the report.

• In total, 27 females receiving radiation therapy completed the study:  11 were randomized to the sham procedure and 16 were randomized to acupuncture.
• Mean age was 54.1 years (standard deviation = 9.4 years).
• All but one participant had breast cancer.
• Of the sample, 44% had also received chemotherapy (74% of the acupuncture group versus 44% of the sham group).

• Single site
• Magee Womens’ Hospital, Pittsburgh, PA

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

• The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale was measured at baseline and three, six, and 10 weeks.
• Quality of life (QOL) was measured with the Short Form 36 (SF-36) Health Survey at baseline and six and 10 weeks.
• The Cancer-Related Fatigue Distress Scale (CRFDS) was measured at baseline and six and 10 weeks.
• Confounding variables measured included:  Brief Symptom Inventory (BSI-18) and Center for Epidemiologic Studies Depression Scale (CEDS).

FACIT-F scores in the true acupuncture group improved more over time than those in the sham group, but the differences were not significant. QOL and depression scores improved in both groups over time significantly but were not different between the groups. Observations regarding feasibility during the study included:  there was difficulty getting patients enrolled; changes in staff, staffing, and procedures made protocol use difficult; and due to procedures to maintain blinding and use of sham procedures, therapists felt that there was less needle manipulation possible with the protocol used for true acupuncture and felt it was difficult to determine the actual depth of needle insertion. It was also felt that the sham procedure was actually more than sham, although less than true acupuncture, due to skin and pressure stimulation.

It was concluded that feasibility to conduct this type of trial in a large group of patients was low. Findings of this study did not support the use of acupuncture to reduce fatigue in patients receiving radiation therapy.

• The study had a small sample size.
• It was not clear, or discussed, how many patients in either group received one or two sessions per week during the trial or whether any differences were associated with the frequency of treatment.
• It was noted that the sham/placebo control procedures were inadequate to provide a true control.
• There was no standard care comparison group.
• Improvements in fatigue, QOL, and depression over time may have been associated with increased attention from trial participation rather than any effect from study interventions.
• The study was not sufficiently powered, and the sample size was too small to differentiate between the groups and identify the associated effect size.

STUDY PURPOSE: To examine the effect of oral nutritional interventions on outcomes among patients with cancer

• FINAL NUMBER STUDIES INCLUDED = 13 in systematic review, 9 included in meta-analysis
• TOTAL PATIENTS INCLUDED = 1,414
• SAMPLE RANGE ACROSS STUDIES: 31–358
• KEY SAMPLE CHARACTERISTICS: Various tumor types receiving adjuvant or neo adjuvant chemotherapy or radiotherapy

• PHASE OF CARE: Active anti-tumor treatment 

• QOL and Functional Scales on EORTC: no significant effects 
• Fatigue: no significant effects
• Dyspnea: mean difference = –2.9 (95% CI [–4.0, –1.8], p < .001) (six studies)
• Loss of appetite: mean difference = –2.35 (95% CI [–4.48, –0.22], p = .03) (seven studies)
• There was no effect seen on survival and effects on body weight and energy intake was inconsistent.

Analysis indicates that oral nutritional interventions were associated with significant improvement in dyspnea and appetite symptom scales. It is unclear what the specific impacts of dietary counseling versus oral nutritional supplements were on these outcomes.

• Few studies retained in meta-analysis that addressed high heterogeneity.
• Outcomes analyzed were based on only single-item scales on the EORTC.
• Patients varied from those receiving adjuvant treatment to those receiving palliative care treatment.
• Varied length of follow-up from three weeks to two years.

Nutritional interventions such as dietary counseling and oral nutritional supplementation may be helpful in managing symptoms of dyspnea and anorexia in patients cancer. Evidence does not provide strong support due to variability in timing of interventions, the exact nature of the interventions, actual nutritional status of patients included, and the timing of outcome data measurement. Nutritional interventions such as dietary counseling and oral nutritional supplement are low-risk interventions that may be helpful for some patients. Well-designed research and reporting in this area would be helpful to guide practice.

The purpose of the study was to compare the proportion of elderly patients with febrile neutropenia while receiving pegfilgrastim from the first cycle of chemotherapy (proactive) with the proportion with febrile neutropenia using the current practice of receiving pegfilgrastim after observed severe neutropenia or neutropenia-related events.

Patients randomized to either proactive pegfilgrastim (subcutaneous injection 6 mg one time per cycle 24 hours after chemotherapy completion staring with cycle one) or secondary prophylaxis with pegfilgrastim (subcutaneous injection 6 mg one time per cycle 24 hours after chemotherapy completion starting after cycle one) at physician’s discretion.

• 852 total patients
• Patients were age 65 or older
• 64.3% were female, 35.7% were male
• Cancers of the lung, breast, ovary, or non-Hodgkin lymphoma
• Patients with with a life expectancy of three months or longer
• ECOG performance status score of 2 or lower

Multiple outpatient settings in community cancer center across the United States.

• The phase of care was active treatment
• Application was elderly care

Phase IV, open-label, randomized, controlled trial.

• Febrile neutropenia
• Grade 3 or grade 4 neutropenia
• Chemotherapy regimen
• Solid tumor type
• Pegfilgrastim administered
• Dose delay, dose reduction, hospitalization, and antibiotic use
   

For the reduction of febrile neutropenia, pegfilgrastim in all chemotherapy cycles was statistically significantly better than use of pegfilgrastim at the physician’s discretion for both solid tumors (p = 0.001) and non-Hodgkin lymphoma (p = 0.004). Pegfilgrastim throughout cycles showed better results than physician discretion for fewer events of grade 3 or 4 neutropenia, hospitalizations and antibiotic use for both solid tumor and non-Hodgkin groups, and for less dose delay and dose reduction in the solid tumor group.

The most common adverse events related to pegfilgrastim was arthralgia.
 

Pegfilgratim use in older adults undergoing chemotherapy appears safe and effective with use starting in the first cycle for the reduction of neutropenia, febrile neutropenia, grade 3 or 4 neutropenia, hospitalizations, and antibiotic use.

The study was not blinded. Fewer patients with non-Hodgkin lymphoma were able to be randomized to the discretion arm since physicians often wanted pegfilgrastim started early in these patients due to known neutropenic outcomes. It also was unclear as to the amount of pegfilgrastim delivered in the physician discretion arm.

The administration of pegfilgrastim starting with the first cycle of chemotherapy may reduce neutropenic events and related complications in older adults with cancer. Nurses can be at the forefront of advocating for this therapy, administering it, and monitoring patients for effective outcomes and/or adverse events.

To describe the underlying mechanisms, clinical presentation, National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0) severity grading, and strategies to prevent and manage epidermal growth factor receptor inhibitor (EGFRI)-associated skin side effects, emphasizing evidence based practice approaches.

The type of patients addressed was those receiving EGFRIs, including monoclonal antibodies (e.g., cetuximab, panitumumab) and low-molecular-weight tyrosine kinase inhibitor (e.g., gefitinib, erlotinib, lapatinib).

The search strategy in this expert opinion article was not defined.

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

The article provided a table with results from four randomized controlled trials. Algorithms for the treatment of papulopustular rash, xerosis, hyperpigmentation, and paronychia were provided. Each algorithm was based on the grading defined in the NCI CTCAE (version 4.0, May 2009).

General Skin Reactions

Preventative:

• General preemptive or prophylactic recommendations for all patients starting therapy with EGFRIs include the following.
  • Patient education prior to the start of therapy
  • Lifestyle modifications
    • Use thick alcohol–free emollients for overall skin moisturization (e.g., creams, ointments).
    • Avoid frequent, prolonged, hot showers, and use tepid water when showering and washing dishes to minimize xerosis.
    • Avoid excessive sun exposure.
    • Use a broad spectrum of sunscreens (ultraviolet A [UVA] and ultraviolet B [UVB]).
    • Avoid alcohol-based products (e.g., lotions).

Rash

Preventative:

• The authors developed an algorithm for preventing and managing EGFRI–induced papulopustular rash. The various treatments were based on severity grading in the NCI CTCAE scale.
• Grade 0:
  • Minocycline 100 mg orally once on the day of chemotherapy for the first eight weeks of therapy
  • Doxycycline 100 mg orally BID one day prior to the start of chemotherapy for the first six weeks of therapy, skin moisturizer, and sunscreen (para-aminobenzoic acid [PABA] free, sun protection factor [SPF] ≥ 15, and UVA and UVB protection)
  • 1% hydrocortisone cream BID for the first six weeks of therapy
  • Skin moisturizing cream
  • Give gentle skin care instructions.

Treatment:

• Grade 1:
  • Continue anticancer agent at current dose and monitor for changes in severity.
  • Give hydrocortisone 2.5% cream and clindamycin 1% gel daily.
  • Reassess after two weeks (either by healthcare professional or patient self-report); if the reactions worsen or do not improve, proceed to the next step.
• Grade 2:
  • Continue anticancer agent at current dose and monitor for change in severity.
  • Give hydrocortisone 2.5% cream and doxycycline or minocycline 100 mg BID.
  • Reassess after two weeks (either by healthcare professional or patient self-report); if reactions worsen or do not improve, proceed to the next step.
• Grade 3:
  • Modify dose as per package insert.
  • Obtain bacterial or viral cultures if infection is suspected and continue treatment of skin reactions with the following.
    • Give hydrocortisone 2.5% cream, doxycycline or minocycline 100 mg BID, and prednisone 0.5 mg/kg for five days.
    • Reassess after two weeks. If reactions worsen or do not improve, then dose interruption or discontinuation per the package insert may be necessary.

Xerosis

Prevention:

• The authors developed an algorithm for preventing and managing EGFRI–induced xerosis. The various treatments were based on severity grading using the NCI CTCAE scale.
• Grade 0: Prophylactic therapy with sunscreen SPF (≥ 30), moisturizing creams, gentle skin care instructions, use of tepid water when showering or washing dishes, use of oil-in-water creams, and avoidance of alcohol–based skin care products or antibacterial soaps.

Treatment:

• Grade 1:
  • Continue anticancer agent at current dose and monitor for changes in severity.
  • Apply over-the-counter (OTC) moisturizing cream or ointment to the face BID and ammonium lactate 12% cream to the body BID.
  • Reassess after two weeks (either by healthcare professional or patient self-report); if reactions worsen or do not improve, proceed to the next step.
• Grade 2:
  • Continue anticancer agent at current dose and monitor for changes in severity.
  • Apply OTC moisturizing cream or ointment to the face BID and ammonium lactate 12% cream or salicylic acid 6% cream to the body BID.
  • Reassess after two weeks (either by healthcare professional or patient self-report); if reactions worsen or do not improve, proceed to the next step.
• Grade 3:
  • Modify dose as per package insert; obtain bacterial or viral cultures if infection is suspected.
  • Continue treatment of skin reactions with the following. Apply OTC moisturizing cream or ointment to the face BID, ammonium lactate 12% cream or salicylic acid 6% cream to the body BID, and triamcinolone 0.25% cream to eczematous areas BID.
  • Reassess after two weeks. If reactions worsen or do not improve, then dose interruption or discontinuation per the package insert may be necessary.

Hyperpigmentation

Prevention:

• The authors developed an algorithm for preventing and managing hyperpigmentation. The various treatments were based on severity grading in the NCI CTCAE scale.
• Grade 0: Prophylactic therapy includes applying sunscreen (SPF ≥ 30) to the face, ears, neck, arms, and hands when exposed to the sun, as well as use of hats and protective clothing.

Treatment:

• Grade 1:
  • Continue anticancer agent at current dose and monitor for changes in severity.
  • Ensure no associated dermatitis (e.g., erythema, rash, edema) exists that should be treated with triamcinolone 0.1% cream.
  • Treat with hydroquinone 4% cream BID and use sunscreen.
  • Reassess after two weeks (either by healthcare professional or patient self-report); if reactions worsen or do not improve, proceed to the next step.
• Grade 2:
  • Interrupt treatment until severity decreases to grade 0 to 1.
  • Continue treatment of skin reactions with application of hydroquinone 4% cream BID to affected areas and strict sun protection.
  • Reassess after two weeks (either by healthcare professional or patient self-report). If reactions worsen or do not improve, then dose interruption or discontinuation per protocol may be necessary.

Paronychia

Prevention:

• The authors developed an algorithm for preventing and managing paronychia. The various treatments were based on severity grading using the NCI CTCAE scale.
• Grade 0: Prophylactic therapy with moisturizing creams, gentle skin care instructions, teaching patients to avoid wearing tight shoes that will exert excessive friction and pressure on the periungual tissues, and teaching patients to avoid frequent water immersion or touching harsh chemicals with their hands and feet.

Treatment:

• Grade 1:
  • Continue anticancer agent at current dose and monitor for changes in severity.
  • Use topical antibiotics and vinegar soaks (soaking fingers or toes in a solution of white vinegar in water [1:1 concentration] for 15 minutes daily).
  • Reassess after two weeks (either by healthcare professional or patient self-report); if reactions worsen or do not improve, proceed to the next step.
• Grade 2:
  • Continue anticancer agent at current dose and monitor for changes in severity.
  • Treat with systematic (oral) antibiotics, vinegar soaks, and silver nitrate or Monsel‘s solution, applied weekly.
  • Reassess after two weeks (either by healthcare professional or patient self-report); if reactions worsen or do not improve, proceed to the next step.
• Grade 3:
  • Modify dose as per package insert.
  • Obtain bacterial or viral cultures if infection is suspected and continue treatment of skin reaction with systematic (oral) antibiotics, vinegar soaks, and silver nitrate or Monsel‘s solution, applied weekly; consider nail avulsion.
  • Reassess in two weeks. If reactions worsen or do not improve, then dose interruption or discontinuation per package insert may be necessary.

This expert opinion article cannot be considered a consensus guideline because it lacks clear comprehensive search and design strategies, clear evaluation of evidence, and a description of the method used to apply that evidence in the development of the recommendation.

A variety of interventions have been studied to prevent or manage various EGFRI-induced skin reactions, including papulopustular rash, xerosis, hyperpigmentation, and paronychia. Although 76 references were cited, this is an expert opinion article based on the lack of clear comprehensive search and design strategies, unclear evaluation of the evidence, and lack of description of the method to apply that evidence in development of the recommendation.

The authors commented on the lack of evidence-based practice recommendations for preventing and managing skin reactions caused by EGFRIs. The authors stated, “The overall lack of adequate data from prospective RCTs and lack of evidence-based standardized guidelines is reflected by differences in treatment methods utilized by clinicians.” The authors also stated, “The relative paucity of clinical data arising from prospective, large, and placebo-controlled randomized controlled trials has been the major limitation of the currently available treatments.”

Considering the frequent use of EGFRIs, healthcare providers should be familiar with these toxicities, as well as available prevention and management strategies.

Implications for nursing practice include using the tables and algorithms in this article as practical tools to prevent or manage several types of EGFRI-induced skin reactions.