To compare the efficacy and safety of netupitant plus palonosetron (NEPA) compared to palonosetron alone in preventing chemotherapy-induced nausea and vomiting (CINV)

Chemotherapy-naïve patients receiving anthracycline- or cyclophosphamide-based chemotherapy were randomized to receive a single dose of PO NEPA (300 mg netupitant plus 0.50 mg palonosetron) and 12 mg dexamethasone or a single dose of 0.5 mg PO palonosetron and 20 mg dexamethasone on day 1, cycle 1, of their chemotherapy. Delayed (25-120 hours post chemotherapy) CINV was evaluated as the primary end point.

• N = 1,455 (participated in a total of 5,969 chemotherapy cycle extension)   
• MEDIAN AGE = 54 years
• MALES: 2%, FEMALES: 98%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Solid tumor cancer, 98% with breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Aged older than 18 years; chemotherapy-naïve; anthracycline- or cyclophosphamide-based chemotherapy; European Cooperative Oncology Group (ECOG) score of 0, 1, or 2; not receiving prolonged chemotherapy from day 1-5; not receiving abdominal radiotherapy; no bone marrow transplantation; did not received any antiemetics 24 hours before chemotherapy and did not experience anticipatory nausea and vomiting

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Multinational

PHASE OF CARE: Active antitumor treatment

Double-blind, randomized

• Diary: Emesis episodes and rescue medications used from 0-120 hour each cycle
• Visual analog scale (VAS) for nausea from 0 (no nausea) to 100 (nausea as bad as it could be)
• Proportion of patients with complete response (0-120 hours)
• Review treatment emergent adverse effects, ECG, troponin levels

Participants who received NEPA and dexamethasone reported complete remission (no emesis or rescue antiemetics) significantly more than participants who received palonosetron and dexamethasone (p ≤ 0.001).

NEPA and dexamethasone may offer more control over CINV compared to palonosetron and dexamethasone.

• Measurement validity/reliability questionable
• Using VAS for nausea and vomiting

Combination antiemetic therapies have been shown to provide more relief from CINV compared to single agents. The results of this study demonstrated that NEPA given with dexamethasone did prevent CINV better than palonosetron and dexamethasone.

To compare two treatments (palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3) for the management of chemotherapy-induced nausea and vomiting (CINV) in the overall study period (days 1–5) and to show comparison between the two treatments in complete response (CR) rates

• At the first cycle of chemotherapy, patients were randomly assigned to receive one of two treatment regimens. Group one received 0.25 mg palonosetron plus 8 mg IV dexamethasone on day 1 and placebo on days 2 and 3, and group two received 0.25 mg palonosetron plus 8 mg dexamethasone on day 1 and 4 mg oral dexamethasone twice a day on days 2 and 3.
• Patients recorded emetic episodes, use of rescue medication, and daily nausea ratings of nausea in diaries.
• Patients were allowed to take rescue medication, and the choice of rescue medication was at the discretion of the individual physician, except that no phenothiazines were allowed.

• The study consisted of 300 participants.
• Mean age was 51.6 years old (SD = 10.11 years).
• The sample was 100% female.
• Participants were chemotherapy-naïve patients with breast cancer receiving moderately emetogenic chemotherapy (MEC).

The study was conducted at multiple outpatient settings in Austria, Germany, Italy, and Spain.

This was a double-blind, randomized, controlled study.

• Patients used diaries to record date and time of emetic episodes, use of rescue medication, daily nausea ratings on a 0-10 visual analogue scale (VAS). 
• CR rate, defined as no emesis and no rescue medication during overall period (days 1–5), was recorded for acute phase (day 1) and delayed periods (days 2–5).
• Maximum severity of nausea (MSN) was recorded in daily and overall phases.
• Time-to-treatment failure (time to first emetic episode or time to first use of rescue medication) was recorded.
• Functional Living Index—Emesis (FLIE) was used in the screening phase and on day 6.
• Adverse events were recorded.

• More than 70% of patients had no emesis.
• CR was not significantly different in the overall, acute, and delayed phases between study groups. However on day 3, patients who received palonosetron plus dexamethasone on days 1–3 experienced less emesis (p = 0.004) and lower MSN (p = 0.028).
• Time-to-treatment failure and use of rescue medication was similar between groups.
• FLIE score and percentage of adverse events was not significantly different between groups.

• The palonosetron with single-day dexamethasone dosing regimen offered high and similar protection as palonosetron with 3-day dosing of dexamethasone in terms of CR rates and patient performance.
• In some cases, the protection was insufficient on day 3, and the benefits of dexamethasone needed to be weighed against the increased risk of potential side effects.

• The sample was only women who were chemotherapy naïve receiving MEC regimens. These findings may not be generalizable to other groups, particularly as some research has shown differences in antiemetic results between men and women.
• Patient compliance with daily diary recordings was not discussed.

• With chemotherapy-naïve patients with breast cancer receiving chemotherapy, palonosetron plus dexamethasone provides fairly good control over CINV.
• In patients whose antiemetic-related side effects have been bothersome, a palonosetron plus single-dose dexamethasone regimen could be an option.
• In both groups, more than half of patients still had nausea on day 1 and about one-third still had nausea in the delayed period, pointing to the need for individualization of ongoing management.

To determine if the granulocyte–colony-stimulating factor (G-CSF) biosimilar filgrastim had similar outcomes for adults and older adult patients actively undergoing treatment for cancer

This was a prospective observational study of patients prescribed biosimilar filgrastim in 140 centers in 12 European countries.

• N = 1,447 patients; 41% were older than age 65 years (cut-off at age 65 years) and put into the older adult category   
• AGE = Adults aged 18 years or older
• MALES: 49.8% older adult, 31% adult
• FEMALES: 50.2% older adult, 69% adult
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Stage III–IV breast, ovarian, bladder, and lung cancer; metastatic prostate cancer as well as stage III–IV large B-cell lymphoma and multiple myeloma

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: 12 European countries

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

Prospective observational

Comparative analysis of various components outlined by the authors

No statistically significant differences existed in the rates of chemotherapy-induced neutropenia and febrile neutropenia episodes between either groups. G-CSF support is equally important in both groups. Older adult patients with underlying chronic conditions may be at higher risk for febrile neutropenia; in both groups, it is important to provide timely prophylaxis.

Timely G-CSF support is important in both older adult and adult patients receiving myelotoxic chemotherapy.

Nurses need to be aware of G-CSF administration for patients after chemotherapy. Independent of age group, it is important that patients receiving specific regimens get timely G-CSF treatment to prevent neutropenia duration.

The purpose of this article was to update existing guidelines for prophylactic granulocytye–colony-stimulating factor (G-CSF). The article focuses on patients receiving chemotherapy, not limited to one definition of febrile neutropenia (FN). No studies with pediatric patients or patients with leukemia were included.

This guideline resource used a process where articles were rated using the table listing below.

Level                Type of Evidence
A                        Evidence of type I or consistent findings from multiple studies of types II, III, or IV
B                       Evidence of types Ii, II, or IV and findings are generally consistent
C                       Evidence of types Ii, II, or IV, but findings are inconsistent
D                       Little or no systematic empirical evidence 

Information from papers included in meta-analyses were only used to answer questions not included in the meta-analyses. Publications available from Congress presentations previously included as abstracts were only used is they provided answers not yet presented. Authors were contacted if their abstracts were relevant and publications noted as missing or “in press” were included.

Regarding a search strategy, the MEDLINE, PreMEDLINE, EMBASE, and Cochrane Library databases were used.

Key words included antineoplastic agents, filgrastim, granulocyte–colony-stimulating factor, lenograstim, neoplasms, neutropenia, pegfilgrastim, and guideline

Articles were included if they were recent reviews, any primary papers deemed relevant, and meta-analyses subject to manual review. In addition to filgrastim and pegfilgrastim, two filgrastim biosimilar molicules, XMO2 and EP2006, daily G-CSFs have been approved in Europe. 

Articles were excluded if their studies included patients younger than age 18 years or patients with a diagnosis of leukemia.
 

• The phase of care is active chemotherapy treatment
• Applications is adult patients receiving chemotherapy.
   

Recommendations  Primary prophylactic G-CSF is recommended for patients at risk and should be started 24–72 hours following completion of the first cycle.

Step I:

• Assess frequency of FN associated with planned chemotherapy regimen, and reassess with each cycle.
• If FN risk is less than10%, G-CSF prophylaxis is not recommended. If FN risk is greater than 20%, prophylactic G-CSF is recommended.
• If FN risk 10%–20%,  proceed to step 2.

Step 2: 

• Assess for high risk: age older than 65 years.  
• Increased risk (level I, II evidence): Advanced disease, history of prior FN, no antibiotic prophylaxis, no G-CSF use
• Other factors (level III, IV evidence): Poor performance/nutritional status, female, Hgb < 12 g/dl, liver, renal, cardiovascular disease
• and then proceed to step 3

Step 3: 

• Define the patient’s overall FN risk for planned chemotherapy regimen.
• If overall FN risk is greater than 20%
• Secondary prophylaxis: Start G-CSF if neutropenic event occurred in previous cycle.

Provides percent risk for development of FN for some tumor types based on chemotherapy regimen. Identifies additional risk factors, but provides little guidance on how to use these to calculate an increase in risk that would warrant prophylactic G-CSF.
 

The article included results from an updated literature search to identify patient and chemotherapy regimen risk factors for developing FN, use of prophylactic G-CSF, G-CSF with existing FN, impact of overall FN risk on G-CSF use, and choice of G-CSF formulation. It was difficult to identify new information as recommendations were combined with existing recommendations.

To evaluate the safety and efficacy of palonosetron at two different doses (0.25 mg versus 0.75 mg) compared with a single dose of 32 mg ondansetron in preventing chemotherapy-induced nausea and vomiting (CINV) after highly-emetogenic chemotherapy

Patients were assigned to one of three treatment arms: palonosetron 0.25 mg, palonosetron 0.75 mg, and ondansetron 32 mg.

The  study consisted of 673 patients, and final data were reported on 667 patients.

This was a phase III, multinational, randomized, double-blind, double-dummy, stratified, parallel-group, active-comparator trial.

• Patient diaries were used to record emetic episodes, nausea, and use of rescue medications.
• The Functional Living Index-Emesis (FLIE) was used.

Equal results were reported for palonosetron and ondansetron in the first 24 hours. In the delayed and overall phases, palonosetron (regardless of dose) was associated with higher complete response (CR) rates compared with ondansetron.

To evaluate the safety and efficacy of NEPA (a combination of netupitant plus palonosetron) compared to palonosetron (PALO) alone

During cycle 1 of moderately emetogenic chemotherapy, patients received either a single dose of NEPA (a combination of 300 mg netupitant and 0.50 mg palonosetron) plus 12 mg dexamethasone, or a single dose of 0.50 mg palonosetron (PALO) plus 20 mg dexamethasone. Patients were randomized and stratified by region. Matching placebos were used for blinding in all groups. Metoclopramide tablets were provided for breakthrough, though treating physicians could select another medication. Data were collected daily on days 1–6 after chemotherapy (0–120 hours).

• N = 1449  
• MEDIAN AGE = 54 years
• MALES: 1.9%, FEMALES: 98.1%
• KEY DISEASE CHARACTERISTICS: Primarily breast cancer (97.5%)
• OTHER KEY SAMPLE CHARACTERISTICS: Chemotherapy-naïve patients receiving moderately emetogenic chemotherapy with an ECOG performance status ≤ 2

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

PHASE OF CARE: Active antitumor treatment

Phase 3 trial, multicenter, randomized, double-blind, double-dummy, parallel group design

• Patient diary (timing and duration of emetic episode, severity of nausea, rescue medications needed)
• Visual analog scale (VAS) of pain
• The Functional Living Index-Emesis (FLIE) 
• Primary endpoint: Complete response (CR)

A significant number of patients in the NEPA group achieved CR when compared to patients in the PALO group overall (p = 0.001), in the delayed phase of treatment (p = 0.001), and during the acute phase of treatment (p = 0.047).

NEPA, the combination of netupitant and palonosetron, was demonstrated to be safe and more effective than palonosetron alone in producing CR during the acute, delayed, and overall phases of treatment in patients receiving cycle 1 of moderately emetogenic therapy.

• Risk of bias (sample characteristics)
• Other limitations/explanation: More than 98% of the participants in the study were women. Of those, more than 97% were diagnosed with breast cancer.

Chemotherapy-induced nausea and vomiting (CINV) guidelines recommend antiemetic therapies targeting multiple pathways involved in emesis. NEPA, the novel combination of netupitant and palonosetron, uses an NK1 receptor antagonist and a 5-HT3 receptor antagonist to maximize CINV control. NEPA was shown to be more effective than palonosetron alone in producing CR during the acute, delayed, and overall phases of cycle 1 of moderately emetogenic therapy. The majority of this sample, however, were women diagnosed with breast cancer. The findings may not be generalizable to males or to other types of cancer.

PURPOSE: To evaluate the use of granulocyte-colony stimulating factor (G-CSF) in adult patients receiving chemotherapy for cancer

TYPES OF PATIENTS ADDRESSED: Adult patients receiving chemotherapy for cancer

PROCESS OF DEVELOPMENT:

The following questions were applied by the European Organisation for Research and Treatment of Cancer (EORTC) G-CSF Guidelines Working Party.

In adult patients with cancer receiving chemotherapy:

1. Is there evidence that patient-related factors increase the risk of febrile neutropenia (FN)?
2. Is there evidence that certain chemotherapy regimens increase the risk of FN?
3. Is there evidence that some patients are more at risk for severe morbidity as a result of an FN episode?
4. Is there evidence to support the use of G-CSF when there is a 20% risk level for FN?
5. Is there evidence to support the use of G-CSF to
   1. Maintain the correct dose of chemotherapy and relative dose intensity and density?
   2. Improve overall and progression-free survival?
6. Is there evidence to support the use of G-CSF to enable the delivery of dose-dense and -intense chemotherapy
   1. By increasing the dose?
   2. By withdrawing one drug and increasing the dose of the remaining drugs?
   3. By increasing the dose frequency?
7. Is there evidence to support the use of G-CSF to reduce the risk of infection-related mortality?
8. Is there evidence to support the use of G-CSF to reduce the incidence of FN?
9. Is there evidence to support the use of G-CSF for the treatment of ongoing FN?
10. Is there evidence to support the use of different G-CSFs?

The article describes guidelines prepared by the G-CSF Guidelines Working Party of the EORTC to systematically review available published data and derive evidence-based recommendations on the appropriate use of G-CSF in adult patients receiving chemotherapy for cancer.

The following are levels of evidence applied by the EORTC G-CSF Guidelines Working Party.

• Level I: Evidence obtained from meta-analysis of multiple, well-designed, controlled studies or from high-power randomized, controlled clinical trial
• Level II: Evidence obtained from at least one well-designed experimental study or low-power randomized, controlled clinical trial
• Level III: Evidence obtained from well-designed, quasi-experimental studies such as nonrandomized, controlled single-group, pre-post, cohort, time, or matched case-control series
• Level IV: Evidence obtained from well-designed, non-experimental studies such as comparative and correlational descriptive and case studies
• Level V: Evidence obtained from case reports and clinical examples

The following grades of recommendations were applied by the EORTC G-CSF Guidelines Working Party.

• Grade A: There is evidence of type I or consistent findings from multiple studies of types II, III, or IV.
• Grade B: There is evidence of types II, III, or IV, and findings are generally consistent.
• Grade C: There is evidence of types II, III, or IV, but findings are inconsistent.
• Grade D: There is little or no systematic empirical evidence.

DATABASES USED: MEDLINE, PreMEDLINE, EMBASE, and the Cochrane Library.

INCLUSION CRITERIA: Articles selected were published in English from December 31, 1994–September 16, 2005. Reference lists of the identified meta-analyses were interrogated manually, and any primary papers considered relevant were included. Abstract books from key international congresses were searched manually to identify relevant evidence presented at meetings from 2003–2005.

EXCLUSION CRITERIA: Studies involving children younger than 18 years of age or patients with leukemia were excluded, as were cost analyses, as these lack international applicability. Relevant articles “in press” and additional papers identified by members of the working party were included in limited instances.

Recommendation 1: Patient-related risk factors for increased incidence of FN

• Patient-related risk factors should be evaluated in the overall assessment of FN risk prior to each cycle of chemotherapy. Particular consideration should be given to the elevated risk of FN for patients aged 65 years or older. Other adverse risk factors that may influence FN risk based on level I and II evidence included advanced stage of disease, experience of previous episode(s) of FN, and lack of G-CSF use and antibiotic prophylaxis. However, please note that the indiscriminate use of antibiotic prophylaxis is not recommended by either the Working Party or the EORTC Infectious Disease Group. Risk factors that may influence FN risk based on level III and IV evidence included poor performance and/or nutritional status, female gender, hemoglobin less than 12 g/dl, and liver, renal, or cardiovascular disease.
• Recommendation grade B

Recommendation 2: Chemotherapy regimens associated with increased risk of FN

• Consideration should be given to the elevated risk of FN with certain chemotherapy regimens. The risk of FN for certain chemotherapy regimens is summarized in Table 4 of the original paper.
• Recommendation grade A/B (depending on the evidence for each chemotherapy regimen)

Recommendation 3: G-CSF to support chemotherapy

• In situations in which dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF should be used as a supportive treatment. If reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis should be used to maintain chemotherapy. Examples of this could be when the patient is receiving adjuvant or potentially curative treatment, or when the treatment intent is to prolong survival. When this is not crucial, use of less myelosuppressive chemotherapy or dose and schedule modifications should be considered.
• Recommendation grade A

Recommendation 4: Impact of the overall FN risk on G-CSF use

• The risk of complications related to FN should be assessed individually for each patient. When assessing FN risk, the clinician should take into account patient-related risk factors, the chemotherapy regimen and associated complications, and treatment intent. If the patient is at more than 20% overall risk of FN, prophylactic G-CSF is recommended. With chemotherapy regimens associated with an FN risk of 10%–20%, particular attention should be given to the assessment of patient characteristics that may increase the overall risk of FN.
• Recommendation grade A

Recommendation 5: G-CSF in patients with existing FN

• Treatment with G-CSF for patients with solid tumors and ongoing FN is indicated only in special situations. These are limited to those patients who are not responding to appropriate antibiotic management and who are developing life-threatening infections (e.g., severe sepsis, septic shock).
• Recommendation grade B

Recommendation 6: Choice of formulation

• Filgrastim, lenograstim, and pegfilgrastim have clinical efficacy, and the authors recommend the use of any of these agents to prevent FN and FN-related complications, where indicated.
• Recommendation grade A

To characterize the antiemetic treatment response of aprepitant when combined with ondansetron and dexamethasone compared to ondansetron and dexamethasone alone, in multiple patient populations receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC)

Study participants had been diagnosed with lung, breast, gastrointestinal (GI), and genitourinary (GU) tumor types and were included in four previously completed randomized control trials. Authors selected the articles for review. Inclusion and exclusion criteria were outlined for each study.

All patients were in active antitumor treatment.

The results of the post hoc analysis of the pooled data demonstrated that complete antiemetic responses were observed in a higher proportion of both HEC and MEC treated patients for all tumor types. For HEC treated patients, significant differences were found in GU (61% versus 44.7%, p = 0.001), GI (68% versus 45%, p = 0.013), and lung cancers (73% versus 53%, p = 0.001). In MEC-treated patients, a significant difference was found in breast cancer (54.9% versus 43.9%, p = 0.0001). Complete response (no vomiting and no rescue medications) following MEC ranged from 54.9% in the breast cancer group to 76% in the lung cancer group.

This analysis demonstrates the consistent efficacy of aprepitant as part of an antiemetic regimen across different tumor types and chemotherapy regimens. The authors recommend the use of an antiemetic regimen that includes aprepitant prior to the first cycle, noting that it will prevent anticipatory chemotherapy-induced nausea and vomiting (CINV) in those patients who respond to the preventative measures.

• This was not a systematic review but, rather, a report of four pooled studies examined by post hoc analysis. 
• The sample size for some of the tumor types was small. 
• This article did not address nausea but, instead, focused on vomiting and use of rescue antiemetic medications.
• The studies were believed to be from randomized trials sponsored by Merck to test efficacy of Amend.

Evidence supports the use of aprepitant in combination with other antiemetic medications for patients receiving MEC and HEC. This supports current understanding of multiple pathways leading to CINV.

To describe commonly used therapies that National Comprehensive Cancer Network (NCCN) Task Force members agreed are appropriate standards of care to manage dermatologic and ocular toxicities that occur in patients with cancer being treated with epidermal growth factor receptor (EGFR) inhibitors.

NCCN Task Force members reviewed available published data on treating toxicities associated with EGFR inhibitors, reviewed data from the treatment of clinically similar toxicities from different etiologies, and shared their expert opinions. Through this process, they developed recommendations for managing dermatologic and ocular toxicities associated with EGFR inhibition in patients with cancer. 

The databases searched were not identified specifically. The authors stated their recommendations were supported only by anecdotal evidence.

Search keywords, inclusion criteria, and exclusion criteria were not provided.

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

Modifying EGFR Inhibitor Therapy

• Brief dosing interruptions can be helpful in managing high-grade EGFR-inhibitor–associated skin and ocular toxicities. These toxicities may lessen over the course of one to two weeks, and then reintroduction of the EGFR inhibitor often is feasible.
• The role of dose reduction remains uncertain. The reproducible relationship between rash and survival for all EGFR antagonists suggests, but does not prove, that maintaining full dose in patients with rash may be beneficial.

Topical Therapies for Rash

Prophylactic/Mitigating Treatments:

• Long-term prophylactic topical mupirocin ointment can be used in the nose to prevent Staphylococcus aureus colonization, especially for patients with recurrent infection.

Reactive Treatments: 

• Topical steroids (low-strength on the face; medium strength on the body) and topical antibiotics (e.g., clindamycin, erythromycin) are based on expert reference and clinical experience, rather than data from randomized clinical trials.
• Petroleum jelly, ammonium lactate, or dilute hydrogen peroxide soaks with gentle debridement may remove excessive formation of yellow crusts and debris in severe skin rash.
• If superinfection is suspected (because of excessive induration and erythema, the presence of a dominant lesion that appears larger and more inflamed than the remainder of the lesions, or purulent drainage), then the site should be cultured to determine the organism and sensitivity. Positive cultures may be evidence of infection or colonization, and clinical judgment is needed to evaluate culture results.
• Pulsed dye laser and intense pulsed light may effectively decrease the erythema and prominence of telangiectatic vessels (dilated blood vessels).
• Postinflammatory hyperpigmentation may fade through the use of hydroquinone, azelaic acid, topical retinoids, or laser-based therapies.

Systemic Therapies for Rash

Prophylactic/Mitigating Treatments:

• These treatments are used to decrease the severity of rash.
• Oral antibiotics include tetracycline (500 mg BID), minocycline (100 mg daily), and doxycycline (100 mg BID).
• Multiagent prophylactic skin treatment (Skin Toxicity Evaluation Protocol With Panitumumab [STEPP] study—randomized trial) includes oral doxycycline (100 mg BID), topical corticosteroids (1% hydrocortisone), skin moisturizer, and sunscreen.
• Sunscreens that are non–alcohol based and physical sunblocks (e.g., zinc oxide, titanium dioxide) with 30 sun protection factor (SPF) that block ultraviolet A (UVA) and ultraviolet B (UBV) light should be applied thickly. 
• A topical vitamin K3 analog, menadione, is being investigated in a phase 1 trial for use in reducing the skin rash associated with EGFR inhibitors.

Reactive Treatments:

• The following treatments are based on anecdotal reports or nonrandomized studies.
  • Oral antibiotics:  tetracycline, minocycline, and doxycycline
  • Retinoids:  isotretinoin (problem with paronychia) and low-dose acitretin (oral 10 mg per day)
  • Systemic steroids: May be appropriate in some settings (usually in the inpatient setting) with careful supervision.

Paronychia:

• For bacterial and fungal cultures, treat infection with appropriate oral antibiotics.
• Apply Monsel’s (ferric subsulfate) solution or silver nitrate to bleeding, overgrown tissue.
• Soaks for symptomatic relief include 4% thymol in alcohol, aluminum acetate (Burow's solution), white vinegar (1:10), and bleach (1/4 cup bleach: 3 gallons water).
• Use topical corticosteroid cream (e.g., methylprednisolone) for inflammatory, noninfected paronychia.
• Clip nails, remove embedded nails or possibly the nail plate, and pack the area with cellulose sponge (Surgifoam^®).
• Wear well-fitted shoes or sandals.
• Cushion nail beds for symptomatic comfort.
• Use topical corticosteroid cream (e.g., methylprednisolone) for inflammatory paronychia.

Pruritus:

• Apply cool compresses, sedating antihistamines (diphenhydramine) at evening or bedtime, topical steroids, and topical menthol lotions.
• Give oral gabapentin or pregabalin (100 mg BID).
• For dry skin, minimize the use of soap, increase use of emollients, avoid alcohol-based agents and topical antipruritics (e.g., Aveeno^® Anti-Itch, Sarna^® Ultra).
• Topical agents for the scalp include fluocinonide 0.05%, clobetasol foam, or steroid shampoo.

Xerosis:

• Frequently apply zinc oxide (30%), petroleum jelly, and other thick emollients (e.g., Aquaphor^®, Aveeno, Bag Balm^®, Cetaphil^®, Cutemol^®, Eucerin^®, Vanicream^®).
• Avoid alcohol-based lotions, antibacterial soaps, long baths or frequent water immersion, and contact with harsh chemicals.

Fissuring on the heels or fingertips:

• Do not use Monsel’s solution (ferric subsulfate) on the face. Some NCCN Task Force members believed this solution may increase the size of the fissures and stain tissue.
• Silver nitrate
• Aluminum chloride solution
• Zinc oxide cream (20%–30%)
• Bleach soaks (10 minutes per day) to prevent infection (1/4 cup bleach: 3 gallons water)
• Protective coverings
• Apply cyanoacrylate glue (e.g., Krazy Glue^®, Super Glue^®) to fissures to relieve pain and promote healing. Some patients and healthcare providers prefer cyanoacrylate glue because liquid cyanoacrylate coverings may increase the sensation of burning and delay healing.
• Antibiotics (e.g., doxycycline) for infected fissures

Desquamation:

• Petroleum jelly or other thick emollients (e.g., Bag Balm)
• Mild (neutral pH) soap
• 12% ammonium lactate, 6% salicylic acid, and 20% urea

The NCCN Task Force report described the management of dermatologic and ocular toxicities that occur in patients receiving EGFR inhibitors. Few recommendations were evidence based; however, some commonly used therapies have data supporting their use. 

Implications for nursing practice include integrating the recommendations of the NCCN Task Force into facility algorithms for preventing or managing several types of EGFR-induced skin reactions. Well-designed research is needed in this area.