Burtness, B., Anadkat, M., Basti, S., Hughes, M., Lacouture, M.E., McClure, J.S., . . . Spencer, S. (2009). NCCN Task Force Report: Management of dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. Journal of the National Comprehensive Cancer Network, 7(Suppl. 1), S5–S21.

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.