STEPP Protocol

STEPP Protocol

PEP Topic 
Skin Reactions

STEPP (Skin Toxicity Evaluation Protocol With Panitumumab) refers to a set combination of interventions aimed at the prevention of skin toxicity. The protocol began a day prior to chemotherapy administration and comprised skin moisturizer used daily, sunscreen (sun protection factor [SPF] ≥ 15 with both ultraviolet A [UVA] and ultraviolet B [UVB] protection) applied prior to going outdoors, topical steroid applied to various skin areas at bedtime, and doxycycline 100 mg taken BID. This protocol was used prophylactically rather than as a provision of interventions in response to treatment-related side effects or toxicities.

Effectiveness Not Established

Guideline/Expert Opinion

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.


Purpose & Patient Population:

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.

Type of Resource/Evidence-Based Process:

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.

Phase of Care and Clinical Applications:

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

Guidelines & Recommendations:

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.


  • 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.


  • 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.


  • 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


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

Nursing Implications:

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.

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.

doi: 10.1007/s00520-011-1197-6

Purpose & Patient Population:

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.

Type of Resource/Evidence-Based Process:

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.

Phase of Care and Clinical Applications:

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

Results Provided in the Reference:

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

Guidelines & Recommendations:

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 


  • 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)


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


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

Hair Changes (Increased Hair)


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

 Radiation Dermatitis


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


  • 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



  • Topical: gentle skin instructions


  • 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%)



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


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



  • 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.


  • 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%).



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


  • 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



  • Topical: Diluted bleach soaks; avoid irritants.


  • 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.

Nursing Implications:

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.

Research Evidence Summaries

Lacouture, M.E., Mitchell, E.P., Piperdi, B., Pillai, M.V., Shearer, H., Iannotti, N., . . . Yassine, M. (2010). Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. Journal of Clinical Oncology, 28, 1351–1357.

doi: 10.1200/JCO.2008.21.7828

Study Purpose:

To examine the difference in incidence of specific grade 2 or higher skin toxicities of interest between patients with metastatic colorectal cancer in preemptive and reactive skin treatment groups during a six-week treatment period that included epidermal growth factor receptor inhibitors (EGFR-Is).

Intervention Characteristics/Basic Study Process:

Eligible patients were randomly assigned to preemptive or reactive skin treatment arms. The chemotherapy regimen schedule was a random assignment stratification factor.

The preemptive skin treatment regimen was administered beginning on day –1 (one day before the administration of the first panitumumab dose) and continued through weeks 1 to 6.

Clinical and experimental data suggest that four major alterations occur in the skin of patients treated with EGFR-Is: follicular and interfollicular inflammation, bacterial superinfection, dry skin, and sensitivity to ultraviolet (UV) radiation. The rationale for selection of the preemptive skin regimen was based on those four alterations. The preemptive skin treatment regimen comprised the following.

  • Skin moisturizer applied to the face, hands, feet, neck, back, and chest daily in the morning on rising (rationale: restore the permeability barrier and treat dry skin)
  • Sunscreen (para-aminobenzoic acid [PABA] free, sun protection factor [SPF] ≥ 15, UVA and UVB protection) applied to exposed skin areas before going outdoors (rationale: prevent UV radiation–induced skin toxicity)
  • topical corticosteroid (1% hydrocortisone cream) applied to face, hands, feet, neck, back, and chest at bedtime (rationale: instituted against cutaneous inflammation and pruritus)
  • Semisynthetic tetracycline (doxycycline 100 mg BID) (rationale: anti-inflammatory and antibacterial properties)

The reactive skin treatment regimen comprised any treatments the investigator deemed necessary for the management of emergent skin toxicity and could be administered anytime during weeks 1 to 6. Patients randomly assigned to the reactive skin treatment group were not prohibited from using skin moisturizer or sunscreen at any time during the treatment if they chose to do so.

All patients were monitored weekly from weeks 1 to 7 for compliance with the randomized skin treatment regimen and for skin toxicity assessment.

Sample Characteristics:

  • The study reported on a sample of 95 patients.
  • The sample was 67% male and 33% female in the preemptive skin treatment group, and 55% male and 45% female in the reactive skin treatment group.


  • Multi-site
  • Outpatient
  • United States

Phase of Care and Clinical Applications:

Patients were undergoing the active treatment phase of care.

Study Design:

This was a phase 2, multicenter, open-label, randomized clinical trial.

Measurement Instruments/Methods:

  • Protocol-defined skin toxicities of interest included pruritus, acneform dermatitis, skin desquamation, exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.
  • Dermatology Life Quality Index (DLQI): Assessed patient-reported quality of life (QOL) at screening, weeks 2 to 7, and the week 13 or 14 visit, depending on the skin treatment schedule. The DLQI comprises 10 simple questions to assess QOL in patients with skin disorders. The DLQI is scored on a scale from 0 to 30, where higher scores indicate more QOL impairment.
  • Patient diary: Throughout the skin treatment period, patients completed a daily diary of symptoms and treatment compliance. The diary was shared with study personnel at each weekly clinic visit and was used for case report data entry.


  • The incidence of protocol-specific grade 2 or higher skin toxicities during the six-week skin treatment period was 29% for the preemptive skin treatment group (23% grade 2 and 6% grade 3) and 62% for the reactive skin treatment group (40.4% grade 2 and 21.3% grade 3) (odds ratio, 0.3; 95% confidence interval [0.1, 0.6]).
  • Acneform dermatitis at any grade occurred in 77% of patients in the preemptive skin treatment group and 85% in the reactive skin treatment group.
  • Incidence of pruritus was similar in both groups.
  • Seventeen percent of patients in the preemptive skin treatment group developed paronychia, compared to 36% in the reactive skin treatment group.


The preemptive skin treatment regimen was well tolerated. The incidence of specific grade 2 or higher skin toxicities during the six-week skin treatment period was lower in the preemptive skin treatment group compared with the reactive skin treatment group.


  • The sample size was small (fewer than 100 patients enrolled).
  • The only EGFR-I used to treat patients was panitumumab. Patients who were receiving cetuximab were not included in the study.
  • The study was not blinded.
  • Information was not provided on reactive treatments used for comparison of effectiveness or the stage at which reactive treatments were instituted.
  • Patient compliance results were not reported.

Nursing Implications:

The findings supported the importance of establishing a preemptive, comprehensive skin treatment regimen in patients treated with panitumumab to decrease skin toxicities and improve QOL. The skin toxicities are considered a class-based effect; therefore, these results may be generalized to other EGFR-Is.