Lacouture, M.E., Anadkat, M.J., Bensadoun, R.-J., Bryce, J., Chan, A., Epstein, J.B., Eaby-Sandy, B., . . . MASCC Skin Toxicity Study Group. (2011). Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Supportive Care in Cancer, 19, 1079–1095.

To develop first-generation, evidence-based recommendations for eight epidermal growth factor receptor inhibitor (EGFRI)-associated dermatologic toxicities: papulopustular (acneform) rash, hair changes, radiation dermatitis, pruritus, mucositis, xerosis, fissures, and paronychia.

The type of patients addressed was those receiving EGFRIs.

In this guideline, topic review committees were formed according to expertise to review the literature and develop guidelines for each dermatologic toxicity. Each review committee comprised three members, with a primary reviewer to present the findings of the committee to the Skin Toxicity Study Group. Each committee reviewed from 17 to 35 articles to formulate the recommended guidelines. Randomized clinical trials were considered the best source. The level of evidence and grade of the recommendation were considered. In the absence of experimental evidence, pertinent studies and case reports were presented in conjunction with expert opinion derived from clinical practice. When available, data were extrapolated from other dermatologic conditions with similar clinical or pathologic characteristics (e.g., xerosis, alopecia, hirsutism, pruritus, paronychia, radiation dermatitis).

Databases searched were Ovid, MEDLINE, and Embase.

Search keywords were rash, hair changes, radiation dermatitis, pruritus, mucositis, xerosis, fissures, paronychia, EGFR inhibitors, and recommendations (this information was not stated directly in the article).

Studies were included in the review if they were published before December 2010. 

Studies were excluded if they were published during or after December 2010.

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

Eight tables outlining prophylactic and reactive recommendations were included for papulopustular (acneform) rash, hair changes, radiation dermatitis, pruritus, oral complications, xerosis, fissures, and paronychia.

Papulopustular (Acneform) Rash

Preventive (Weeks 1–6 and 8 of EGFRI Initiation): 

• Systemic: minocycline 100 mg daily (less photosensitizing) and doxycycline 100 mg BID (preferred in patients with renal impairment)
• Topical: hydrocortisone 1% cream with moisturizer and sunscreen BID 

Treatment:

• Systemic: minocycline 100 mg daily (less photosensitizing), doxycycline 100 mg BID (preferred in patients with renal impairment), and isotretinoin at low doses (20–30 mg per day).
• Topical: alclometasone 0.05% cream, fluocinonide 0.05% cream BID, and clindamycin 1% cream

Hair Changes (Hair Loss)

Preventive:

• Topical and Systemic: Follow rash recommendations for scarring alopecia.

Treatment:

• Topical: minoxidil 2% or 5% BID (nonscarring alopecia); class 1 steroid lotion, shampoo, or foam, or antibiotic lotion (scarring alopecia)

Hair Changes (Increased Hair)

Preventive:

• Support interventions (e.g., patient education)
• Treatment: eflornithine and lasers (facial hypertrichosis) and eyelash trimming (eyelash trichomegaly)

 Radiation Dermatitis

Preventive:

• Topical: maintenance of appropriate skin hygiene with gentle cleansing in radiated areas prior to radiation treatment; high-potency topical steroids

 Treatment:

• Topical: maintenance of appropriate skin hygiene with gentle cleansing in radiated areas prior to radiation treatment, moisturizers, antibacterial moisturizers, drying gel or antiseptics (chlorhexidine), hydrophilic dressings, and antibiotics if infected
• Systemic: doxycycline
• Other: blood cultures for fever or signs of sepsis

Pruritus

Preventive:

• Topical: gentle skin instructions

Treatment:

• Systemic: antihistamines (first generation, sedating: hydroxyzine and diphenhydramine; second generation, nonsedating: loratadine), anti-epileptic agents (gabapentin or pregabalin), and doxepin
• Topical: menthol (0.5%–3%), cooling, pramoxine 1%, doxepin, and medium-to-high–potency steroids (triamcinolone acetonide 0.025%, desonide 0.05%, fluticasone propionate 0.05%, and alclometasone 0.05%)

Mucositis

Preventive:

• Topical: benzydamine, steroids, cryotherapy or ice chips, and low-level laser therapy
• Systemic: patient-controlled analgesia
• Other: radiation blocks and intensity-modulated radiation therapy

Treatment:

• Topical: No topical treatments are recommended.
• Systemic: doxycycline

Xerosis

Preventive:

• Topical: bathing techniques: using bath oils or mild moisturizing soaps and bathing in tepid water; regular moisturizing creams
• Other: Avoid extreme temperatures and direct sunlight.

Treatment:

• Topical (mild to moderate): emollient creams packaged in a jar or tub that lacks fragrance or potential irritants; occlusive emollients containing urea, colloidal oatmeal, and petroleum-based creams; exfoliants for scaly areas: ammonium lactate 12% or lactic acid cream 12%; urea creams (10%–40%); salicylic acid 6%; zinc oxide (13%–40%)
• Topical (severe): Use medium-to-high–potency steroid creams (triamcinolone acetonide 0.025%, desonide 0.05%, fluticasone propionate 0.05%, and alclometasone 0.05%).

Fissures

Preventive:

• Topical: Wear protective footwear and avoid friction with fingertips, toes, and heels.

Treatment:

• Topical: thick moisturizers or zinc oxide (12%–40%) creams; liquid glues or cyanoacrylate to seal cracks, steroids or steroid tape, hydrocolloid dressings, and topical antibiotics; bleach soaks to prevent infection; and zinc oxide

Paronychia

Preventive:

• Topical: Diluted bleach soaks; avoid irritants.

Treatment:

• Systemic: tetracyclines, antimicrobials (reserved for culture-proven infection), and biotin for brittle nails
• Topical: corticosteroids and calcineurin inhibitors
• Other: silver nitrate chemical cauterization weekly; nail avulsion

Recommendations were based on randomized clinical trials with control groups when possible. However, because of the lack of high-quality studies investigating EGFRI-associated dermatologic changes, many recommendations were based on expert opinion and consensus.

The authors developed first-generation, evidence-based recommendations for eight EGFRI-associated dermatologic toxicities: papulopustular (acneform) rash, hair changes, radiation dermatitis, pruritus, mucositis, xerosis, fissures, and paronychia. In addition, the authors rated each intervention according to the level of evidence (I–V) and the recommendation grade (A–D). 

The authors proposed that multidisciplinary teams, including radiation and medical oncologists, nurses, dermatologists, pharmacists, oral healthcare providers, and wound care specialists, should assess the occurrence and management of EGFRI-associated dermatologic toxicities. In addition, the Multinational Association for Supportive Care in Cancer (MASCC) EGFRI Skin Toxicity Tool (MESTT) should be used in clinical trials and practice.

Nurses should provide patient education prior to EGFRI therapy to ensure patients can expect, prepare for, and use preventive and treatment approaches to manage the eight toxicities described. In addition, nurses should encourage the multidisciplinary team to collaborate on management of EGFRI-associated dermatologic toxicities.