Corticosteroids

Corticosteroids

PEP Topic 
Skin Reactions
Description 

Corticosteroids are a class of steroid hormones produced in the adrenal cortex and involved in a wide range of physiologic systems such as stress and immune responses, regulation of inflammation, carbohydrate metabolism, and protein catabolism. Corticosteroids can be administered orally, intravenously, or topically and are used for a variety of conditions. Drugs in this class include dexamethasone, methylprednisolone, prednisone, hydrocortisone, and fludrocortisones. Corticosteroids have been examined in the management of anorexia and pain, and specific, individual corticosteroids are typically part of drug regimens for chemotherapy-induced nausea and vomiting. Topical use of specific corticosteroids has been examined for its efficacy in radiodermatitis, skin reactions, mucositis, and prevention of bleeding. Systemic use of steroids has been examined in pain, fatigue, radiodermatitis, and skin reactions.

Effectiveness Not Established

Systematic Review/Meta-Analysis

Anderson, R., Jatoi, A., Robert, C., Wood, L.S., Keating, K.N., & Lacouture, M.E. (2009). Search for evidence-based approaches for the prevention and palliation of hand-foot skin reaction (HFSR) caused by the multikinase inhibitors (MKIs). Oncologist, 14, 291–302.

doi: 10.1634/theoncologist.2008-0237
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Purpose:

To systematically review the literature on the prevention and palliation of multikinase inhibitor (MKI)-associated hand-foot syndrome (HFS) to identify areas for further clinical study and to provide a foundation for evidence-based guidelines for HFS management

Search Strategy:

DATABASES USED: PubMed, Cochrane Database of Systematic Reviews, BIOSIS, and CANCERLIT

KEYWORDS: Hand foot syndrome, hand foot skin reaction, acral erythema, palmar-plantar erythrodysesthesia, acral erythrodysesthesia, Burgdorf reaction, toxic erythema of the palms and soles. Medical subject headings (MeSH) included skin disease, hand injuries, chemically induced, antineoplastic agents, and protein kinase inhibitors. Names of specific agents also were entered into the MeSH search.

INCLUSION CRITERIA: English language clinical studies; meta-analysis, reviews, or practice guidelines; literature through August 31, 2008. Literature was categorized (C) according to the type of agent and cutaneous reaction.

  • C1—Articles pertaining to MKI-associated HFS containing histology, pathogenesis, incidence, quality of life, impact, treatment, or prevention
  • C2—Articles focused on MKI-associated skin reactions other than HFS
  • C3—Articles focused on antineoplastic agents other than MKIs and HFS
  • C4—Articles that did not focus on clinical details of pathophysiology or treatment of HFS (e.g., health policy, study design issues)

EXCLUSION CRITERIA: Conditions other than HFS, topics unrelated to antineoplastic therapy

Literature Evaluated:

TOTAL REFERENCES RETRIEVED = 2,069 abstracts 

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: After screening for inclusion, 350 abstracts (17%) met criteria for inclusion in C1–C4 categories.

Sample Characteristics:

  • FINAL NUMBER STUDIED INCLUDED = 56 articles categorized as C1 were reviewed and evaluated. Only those that fell into this category were discussed in this review. None of the citations on prevention or palliation approaches to HFS were randomized, controlled trials.

Results:

Prevention approaches for MKI-associated HFS included

  • Screening for preexisting plantar hyperkeratosis (e.g., podiatry care)
  • Prophylactic removal of hyperkeratotic areas (e.g., manicure or pedicure before and during treatment to remove hyperkeratosis)
  • Use of prophylactic skin care (e.g., emollients, topical exfoliating products applied to calluses, pedicures, manicures)
  • Protection of pressure-sensitive areas of the hands and feet (e.g., wearing well-fitting, soft shoes; cushioning of callused areas by soft or padded shoes)
  • Use of prophylactic systemic treatments (e.g., administration of prophylactic pyridoxine [vitamin B6], glucocorticoids, cyclooxygenase-2 inhibitors).

The following are recommendations on patient education prior to MKI therapy.

  • Providers are encouraged to listen to patient concerns, offer options to enhance patient comfort, and identify treatment issues early.
  • No studies were found that tested efficacy of patient education approaches for preventing hand-foot skin reactions (HFSRs) (e.g., written materials, videos).

Treatment and palliation for management of HFS symptoms:

  • Grade 1 HFS
    • Dermatology referral and management, as appropriate
    • Use of keratolytics (e.g., 40% urea and/or salicylic acid) to aid in exfoliation of callused areas
    • Cushioning of affected regions with gel inserts in shoes or use of loose-fitting shoes or slippers
    • Frequent application of emollients and creams, especially to palms and soles, to maintain moisture and prevent breaks in skin integrity
    • Analgesics
    • Local/regional cooling (e.g., cool compresses)
    • Foot soaks in magnesium sulfate to soften calluses and reduce pain upon pressure
  • Grade 2 HFS
    • All interventions as outlined for grade 1
    • Dosage or regimen adjustments of MKIs
    • Continue to control symptoms and relieve patient discomfort
  • Grade 3 HFS
    • Topical therapy to reduce symptoms and prevent further progression (e.g., frequent use of creams and lotions, especially to palms and soles of feet; wet disinfectant to treat blisters and erosions; cortisone creams and topical antibiotics for severe forms of HFSRs)
    • Systemic strategies to reduce symptoms and prevent further progression (e.g., pyridoxine may be beneficial in doses of 50–150 mg/day)
    • Dosage or regimen adjustments of MKIs (e.g., interruption of MKI therapy for a minimum of seven days until toxicity is resolved to grade 0 or 1)

Authors stated that no evidenced-based treatment algorithms exist for cutaneous toxicities of the MKIs in the dermatologic or oncologic literature. It was noted that none of these recommendations were based upon strong evidence-based data and that none of the C1 articles were randomized, controlled trials designed to test HFS reactions management. It was revealed that clinical approaches to HFS are largely anecdotal, from case reports, based on practices during clinical trials of antineoplastic treatment, obtained from post-marketing practices, or extrapolated from approaches often used with chemotherapeutic treatments.

Conclusions:

No actual convincing evidence was found in this review for any recommendation identified.

Limitations:

  • Among all the C1 articles reviewed, none were randomized, controlled trials designed to test HFS management approaches.
  • None of the ancillary, observational, or case control studies described in the literature reviewed were designed to test the effectiveness of HFS management interventions.
  • Most information being used is anecdotal or based upon individual provider experience and preference.

Nursing Implications:

This review points to the need for research to test and compare various recommendations for prevention and management of HFS on clinical and patient-centered outcomes.

Research is needed in the following.

  • Appropriate and effective patient education for prevention
  • How often the patient should be seen and assessed for HFS
  • How to accurately diagnose mild HFS and recognize subsequent skin complications
  • How to effectively treat without leading to increased HFS damage and symptoms
  • Providing guidance on the best types of gel inserts, cushions, and soft footwear
  • Identifying treatment strategies that are most effective at all grades of HFS
  • Testing specific emollients or creams for preventive or reactive treatment of MKI-associated HFS

Guideline/Expert Opinion

Balagula, Y., Garbe, C., Myskowski, P.L., Hauschild, A., Rapoport, B.L., Boers-Doets, C.B., & Lacouture, M.E. (2011). Clinical presentation and management of dermatological toxicities of epidermal growth factor receptor inhibitors. International Journal of Dermatology, 50, 129–146.

doi: 10.1111/j.1365-4632.2010.04791.x
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Purpose & Patient Population:

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).

Type of Resource/Evidence-Based Process:

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

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:

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).

Guidelines & Recommendations:

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.

Limitations:

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.

Nursing Implications:

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.  

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.

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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.

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

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.

Gutzmer, R., Becker, J.C., Enk, A., Garbe, C., Hauschild, A., Leverkus, M., . . . Homey, B. (2011). Management of cutaneous side effects of EGFR inhibitors: Recommendations from a German expert panel for the primary treating physician. Journal der Deutschen Dermatologischen Gesellschaft, 9, 195–203.

doi: 10.1111/j.1610-0387.2010.07561.x
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Purpose & Patient Population:

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

The type of patients addressed was adults receiving an EGFRI, including monoclonal antibodies (e.g., cetuximab, panitumumab) and tyrosine kinase inhibitors (e.g., erlotinib, gefitinib, lapatinib).

Type of Resource/Evidence-Based Process:

In this expert opinion article, a panel of German dermatologists met in June 2009 in Frankfurt am Main, Germany, to generate mutual recommendations on the management of cutaneous side effects of EGFRIs. Those recommendations were passed after an internal revision in July 2010. The authors stated the basis of the recommendations was the physicians’ long-term personal experiences with affected patients.

Databases searched were not reported.

Search keywords were EGFR, cutaneous side effects, and papulopustular exanthema.

Studies were included in the review if they were published up to April 2010.

Exclusion criteria were not reported.

Phase of Care and Clinical Applications:

Patients were undergoing the active treatment phase of care.

Guidelines & Recommendations:

General and Preventive Measures for All Patients Receiving EGFRI Therapy:

  • Give patient education regarding various cutaneous side effects, usual time points for manifestation, and positive correlation between early occurring papulopustular exanthems and therapy success and general measures. 
  • The following advice was recommended for preventive skin care procedures for all patients receiving therapy with EGFRIs:
    • Avoid frequent hand washing; daily, long showers; or frequent, long baths.
    • Use mild bath or shower oils or syndets (no soap).
    • Use moisturizers or urea-containing skin care products (e.g., ointment, cream) without fragrances or other skin irritants (no lotion or gel).
    • Avoid sun-tanning parlors, and consistently use sun protection products (light exposure factor > 20) or clothing protection from ultraviolet radiation.
    • Avoid skin contact with irritants such as solvents, disinfectants, and polishes.
    • Avoid activities that mechanically stress the skin (e.g., garden work, carrying heavy objects, hot hair drying).
    • For adequate treatment of preexisting skin diseases, refer to a dermatologist.

Medicinal Prophylaxis of EGFRI Cutaneous Lesions:

  • A few studies on medicinal prophylaxis of papulopustular exanthema have been performed, and their results do not allow for reliable recommendations.
  • Prophylactic treatments included oral tetracycline, minocycline, and doxycycline; topical pimecrolimus; skin moisturizer; and topical sunscreen, glucocorticosteroids, and vitamin K3.

Therapy of the Papulopustular Exanthems on the Face and Trunk:

  • Initiate combined therapy with a topical metronidazole or nadifloxacin-containing ointment and a systemic tetracycline (doxycycline: 50 or 100 mg BID;  minocycline: 50 mg BID; tetracycline: 2–4 x 250 mg daily).
  • Treatment of rash with wound gel containing collagen or lidocaine and topical vitamin K3 is being studied.

Advanced Diagnostics and Therapy for Rash (Usually With a Dermatologist):

  • Obtain microbial diagnostics in papulopustular exanthema.
  • If Demodex mites are detected in the lesions, employ topical metronidazole, a short course of an azelaic acid cream, or a cream containing permethrin.
  • If Pityrosporum yeasts are identified, ciclopirox olamine, clotrimazole, or ketoconazole is recommended.
  • In bacterial superinfection, depending on the antibiogram (usually identification of Staphylococcus aureus), topical therapy with an antiseptic agent (e.g., octenidine) and targeted systemic antibiotic therapy are recommended.
  • For eczematous skin lesions with scaling and pruritus on the trunk, mild-to-moderate potency topical glucocorticosteroids (e.g., hydrocortisone butyrate, methylprednisolone aceponate) are recommended.
  • When clinical features of seborrheic dermatitis or perioral dermatitis are present in the face, pimecrolimus or tacrolimus and a topical antifungal agent (e.g., ciclopirox) may be used.

Therapy of Papulopustular Exanthems on the Scalp:

  • Early treatment with a systemic antibiotic usually offers effective protection from the development of a severe papulopustular rash on the scalp.
  • In patients who develop a superinfection despite administration of a systemic antibiotic, microbiological diagnostics should be performed and therapy based on the antibiogram should be changed to an antibiotic effective against S. aureus (e.g., flucloxacillin).
  • Antimicrobial shampoos may be used.

Treatment Recommendations: Dry Skin and Pruritus:

  • Use of emollients (e.g., urea-containing products), perhaps with the addition of an antiseptic (e.g., triclosan) can be used for dry, sensitive skin.  
  • If marked inflammation exists, a short course of glucocorticosteroid ointment is recommended.
  • If severe inflammation exists, a short course of glucocorticosteroid ointment and an antiseptic is recommended.
  • Topical products containing polidocanol and oral antihistamines can be used on a supplemental basis for dry skin and pruritus.
  • If inflamed skin fissures exist, obtain a referral to a dermatologist.

Treatment Recommendations: Paronychia:

  • In early stages of paronychia, treatment with a topical antifungal agent (e.g., ciclopirox olamine) and a topical antibiotic (fusidic acid) is recommended.
  • In the event of damage to the cuticle, a nail lacquer containing ciclopirox should be applied every two days.
  • Combination of a topical glucocorticosteroid and a disinfectant can be considered.
  • Systemic therapy can include one of the oral tetracyclines, or an oral cephalosporin or quinolone.
  • In advanced or persistent inflammation, the patient should be referred to a dermatologist for further treatment.
  • For severe inflammation, microbiological tests and targeted antibiotic therapy are recommended.
  • Excessive granulation tissue should be removed surgically or with silver nitrate.
     

Nursing Implications:

Effective management of frequent cutaneous side effects is important for tumor therapy. The present recommendations developed by a German expert panel are based on a three-step concept.

  • Patient education and general preventive measures
  • Measures that should be initiated as early as possible by the primary treating physician at the first sign of skin lesions
  • Advanced diagnostics and therapy by a specialized dermatologist

Although the article had 36 references, several interventions (especially in rash—advanced diagnostics and therapy, rash—therapy on scalp, measures for dry skin and pruritus, and therapy of paronychias) do not have a specific reference.

Adequate management of cutaneous side effects is necessary for optimal therapeutic benefit and enhanced quality of life. Because of their visibility, cutaneous side effects are experienced by many patients as a psychological burden that can impair quality of life and often endangers compliance with therapy, or leads to a dose reduction or discontinuation. This article provided nurses with practical recommendations for the prevention and management of cutaneous side effects of EGFRIs.  

Research Evidence Summaries

Drake, R.D., Lin, W.M., King, M., Farrar, D., Miller, D.S., & Coleman, R.L. (2004). Oral dexamethasone attenuates Doxil®-induced palmar-plantar erythrodysesthesias in patients with recurrent gynecologic malignancies. Gynecologic Oncology, 94, 320–324.

doi: 10.1016/j.ygyno.2004.05.027
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Study Purpose:

To evaluate the effectiveness of oral dexamethasone in attenuating or eliminating ​palmar-plantar erythrodysesthesias (PPE) induced by pegylated liposomal doxorubicin (PLD) (Doxil®) in patients with recurrent gynecologic malignancies.

Intervention Characteristics/Basic Study Process:

Patients were initially treated with PLD without dexamethasone (median number of cycles = 5). Patients who experienced grade 2 to 4 PPE had treatment delayed until symptom resolution, and then were retreated without dose reduction.

Patients in group 1 received a tapering oral dexamethasone regimen (8 mg BID) starting one day before infusion for five days, 4 mg BID on day 6, and 4 mg on day 7.

In group 2, patients who were not receiving dexamethasone and experienced grade 2 to 4 PPE had a weekly dose delay for up to two weeks until symptom resolution. If resolution occurred within three weeks of the delay, a 25% dose reduction was made. Patients who had persistent grade 3 or 4 PPE had PLD withdrawn.

Sample Characteristics:

  • The study reported on a sample of 23 patients with recurrent gynecologic malignancies who received PLD 50 mg/m2 on a 28-day cycle from January 1998 to December 2000.
  • Sixteen patients had ovarian cancer, and seven had uterine cancer.

Setting:

University of Texas Southwestern Medical Center in Dallas

Study Design:

This was a prospective, observational trial.

Measurement Instruments/Methods:

National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) was used to assess PPE (grades 1–4).

Results:

  • Nine patients (39%) who received more than five cycles of PLD (50 mg/m2) developed grade 2 to 4 PPE. Median time to PPE was three cycles, and drug treatment was withheld until PPE symptoms resolved.
  • On restarting treatment, six of nine patients who developed PPE received a scheduled tapering dose of oral dexamethasone. All six had complete or near complete resolution of PPE, and all continued treatment without subsequent dose modification or delay for an average of seven cycles.
  • In group 2, three of the nine patients with PPE who did not receive dexamethasone required treatment delays, and doses were reduced.

Conclusions:

Oral dexamethasone appears to be effective in attenuating or eliminating PLD-induced PPE in patients with recurrent gynecologic malignancies.

Limitations:

The sample size was small.

Gerber, P.A., Meller, S., Eames, T., Buhren, B.A., Schrumpf, H., Hetzer, S., ... Homey, B. (2012). Management of EGFR-inhibitor associated rash: A retrospective study in 49 patients. European Journal of Medical Research, 17(1), 4.  

doi:10.1186/2047-783X-17-4
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Study Purpose:

To compare the effectiveness of three established rash-management strategies in EGFR-inhibitor (EGFRI) associated rash development

Intervention Characteristics/Basic Study Process:

Rash severity was assessed during the initial presentation to clinic by applying the EGFR-Induced Rash Severity Score (ERSS). Three different EGFRI rash-management strategies were compared, and each targeted the inflammatory and/or the infectious characteristics of the rash. In stage 1 of the study, 21 patients (ERSS 10.3 to 77.9) were treated topically with mometasone furoate cream (a topical anti-inflammatory) twice daily. In stage 2 of the study, 23 patients (ERSS 12.5 to 67.1)  were treated topically with nadifloxacin 1% cream (a potent topical fluoroquinolone antibiotic) once daily in the morning, in combination with prednicarbate 0.25% cream (a topical glucocorticosteroid) once daily in the evening. In stage 3 of the study, five patients (ERSS > 50) received topical nadifloxacin and prednicarbate 0.25% cream in combination with the systemic retinoid isotretinoin 10–20 mg/day. Rash severity was reassessed after three weeks of specific therapy to manage the dermatologic reaction.

Sample Characteristics:

  • N = 49            
  • AGE = Not reported
  • MALES: Not reported, FEMALES: Not reported
  • KEY DISEASE CHARACTERISTICS: Not reported
  • OTHER KEY SAMPLE CHARACTERISTICS: (1) DRUG: Patients who were treated with either cetuximab (a monoclonal anti-EGFR antibody) or erlotinib (a small molecule EGFR tyrosine kinase inhibitor), and who developed an EGFRI-associated rash at the time of referral to the physician’s clinic. (2) TIMING: Selection was limited to initial patients, and their follow-up visits were made in the timeframe of March 2007 to October 2009. (3) RASH SEVERITY: Patients who presented with ERSS of 10 or higher.  

Setting:

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

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment

Study Design:

Retrospective, uncontrolled, comparative study

Measurement Instruments/Methods:

The EGFR-induced rash severity score (ERSS or WoMoScore) is a skin-specific scoring system that was introduced in 2008. The ERSS is a combined score of the severity of five different aspects of the EGFRI rash (i.e., color of erythema, distribution of erythema, population, postulation, and scaling crusts), and the extent of affected facial area and the total body area involved.  
 
ERSS score ranges are 0 (no skin reaction), 1–20 (mild), 21–40 (moderate), and more than 40 (severe). Rash severity was assessed during initial presentation to the clinic and at three weeks of specific therapy to manage the dermatologic reaction. Statistical analysis was performed using the Student’s t-test.   

Results:

Patients' EGFRI-associated rash severity improved significantly with all three dermatological treatments, which are aligned with recent expert recommendations: topical mometasone furoate cream (p = 0.00009); nadifloxacin 1% cream and prednicarbate 0.25% cream (p = 0.03); and nadifloxacin 1% cream and prednicarbate 0.25% cream plus systemic isotretinoin (p = 0.015).

Conclusions:

In summary, the results demonstrate that EGFRI-associated rashes can be effectively managed by specific dermatologic interventions, including topical glucocorticosteroids, topical antiseptics/antibiotics, and systemic retinoids. Topical mometasone furoate cream was the only therapy that resulted in a complete resolution of all rash symptoms in one patient.

Limitations:

  • Small sample (< 100)
  • Risk of bias (no control group)
  • Risk of bias (no blinding)  
  • Risk of bias (no random assignment)
  • Other limitations/explanation
    • For the sample population, age, sex, and diagnosis were not reported.
    • Statistical comparison of different therapy regimens is limited due to variations in patient numbers and rash severity in each of the three test groups before therapy. Specifically, group 3 had only five patients and the rash severity in all five patients was ERSS > 50 (severe).
    • The study design did not include a control group, which would have been a subgroup of patients with EGFRI rash that was left untreated for the study period (three weeks).
    • In the abstract, the authors state that mild to moderate rashes should be treated with basic measures in combination with other dermatologic treatments. In the discussion section, the authors state, “Notably, all approaches that were analyzed in this study are in line with recent expert recommendations that suggest an escalating strategy for the management of the EGFRI rash with a succession of treatments, as indicated, summarized as follows: intensive skin care in combination with mild cleansers ... .”   The components of “basic measures” or “intensive skin care” were not described, and whether intensive skin care and mild cleansers were included with the other interventions is not delineated in the article.
    • The ERSS system was designed with a non-linear affected area scale emphasizing minor variations in mild patients with face involvement only.   

Nursing Implications:

Nurses should consider treating mild to moderate EGFRI skin rashes with basic skin care measures in combination with topical glucocorticosteroids or combined regimens using glucocorticosteroids and antiseptics/antibiotics. Nurses should be aware that more severe or therapy-resistant rashes may respond with the addition of systemic retinoids.

Katzer, K., Tietze, J., Klein, E., Heinemann, V., Ruzicka, T., & Wollenberg, A. (2010). Topical therapy with nadifloxacin cream and prednicarbate cream improves acneiform eruptions caused by the EGFR-inhibitor cetuximab–A report of 29 patients. European Journal of Dermatology, 20, 82–84.

doi:10.1684/ejd.2010.0806
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Study Purpose:

To evaluate the clinical efficacy of nadifloxacin and prednicarbate cream for treatment of cetuximab-induced acneiform eruptions

Intervention Characteristics/Basic Study Process:

Patients who had acneiform eruptions of varying severity were treated with nadifloxacin 1% cream and prednicarbate 0.25% cream once daily for six weeks. Patients continued their usual use of sunscreens, cleansers, and antihistamines. The severity of eruptions was scored at baseline and after one, two, and six weeks of treatment.

Sample Characteristics:

  • N = 29
  • MEAN AGE = 64.6 years (range = 38–89 years)
  • MALES: 76%, FEMALES: 24%
  • KEY DISEASE CHARACTERISTICS: All patients were receiving cetuximab

Setting:

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

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment

Study Design:

  • Open-label trial

Measurement Instruments/Methods:

Investigator developed skin score calculated from percentage body involvement, percentage facial involvement, and skin lesion scoring on a 3-point scale for erythema and other lesion characteristics.

Results:

A significant reduction in skin score was seen at all time points (p < .05). Subjective symptoms such as pruritus, pain, and tenderness were reported to be improved. The treatment was well tolerated. Two patients reported mild burning and erythema following application of the nadifloxacin cream.

Conclusions:

The combination of topical quinolone and corticosteroid was effective in reducing acneiform eruptions in this group of patients.

Limitations:

  • Small sample (< 30)
  • Risk of bias (no control group) 
  • Risk of bias (no blinding)  
  • Risk of bias (no random assignment)
  • Measurement validity/reliability questionable
  • Other limitations/explanation: The skin score used is well described, but validity and reliability is not clear.

Nursing Implications:

The combination of topical quinolone and steroid may be helpful in treating EGFR-inhibitor associated acneiform rash. This study had several methodological limitations, so it does not provide strong support. Further research in this combination is warranted.

Kollmannsberger, C., Schittenhelm, M., Honecker, F., Tillner, J., Weber, D., Oechsle, K., . . . Bokemeyer, C. (2006). A phase I study of the humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with paclitaxel in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC). Annals of Oncology, 17, 1007–1013.

doi: 10.1093/annonc/mdl042
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Study Purpose:

To evaluate the effectiveness of dexamethasone and pyridoxine on the frequency and severity of palmar-plantar erythrodysesthesia (PPE) in patients with solid tumors receiving pegylated liposomal doxorubicin (PLD).

Intervention Characteristics/Basic Study Process:

Evaluable patients had at least two cycles of therapy. A total of 51 cycles of PLD was applied to the 19 patients. The maximum tolerated dose was 60 mg/m2 every 28 days. In a second step, interval reductions at the highest four weekly doses from 28 to 21 to 14 days were planned. Patients received oral dexamethasone 8 mg BID on days 1 to 5 with vitamin B6 100 mg BID continuously along with PLD.

Sample Characteristics:

  • The study reported on a sample of 19 patients who had solid tumors and were receiving PLD.
  • PLD doses ranged from 40 to 60 mg/m2.

Setting:

  • Department of Medicine at the University of Tuebingen Medical Center in Germany
  • Department of Medicine at the University of Essen Medical Center in Germany

Measurement Instruments/Methods:

PPE was evaluated with a scale from grade 1 to 4. The specific grading scale was not discussed.

Results:

  • Three of seven patients with 21-day PLD intervals developed grade 3 or 4 PPE.
  • At the 28-day PLD interval, grade 3 PPE occurred in only in 1 of 12 patients who were receiving 60 mg/m2 PLD during the third cycle. That patient discontinued dexamethasone on day 2.

Conclusions:

Compared to reported frequencies of up to 25%, the incidence of PPE caused by PLD appeared to decrease with concomitant dexamethasone and vitamin B6.

Limitations:

  • The sample size was small.
  • This was not a randomized clinical trial, and no control or comparison group was used.
  • The description of the measurement tool or method used to grade PPE symptoms was inadequate, and reliability and validity were unclear.

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
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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.

Setting:

  • 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.
     

Results:

  • 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.

Conclusions:

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.

Limitations:

  • 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.  

Mangili, G., Petrone, M., Gentile, C., De Marzi, P., Vigano, R., & Rabaiotti, E. (2008). Prevention strategies in palmar-plantar erythrodysesthesia onset: The role of regional cooling. Gynecologic Oncology, 108, 332–335.

doi: 10.1016/j.ygyno.2007.10.021
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Study Purpose:

To evaluate the effectiveness of strategies to prevent ​palmar-plantar erythrodysesthesia (PPE) incidence, including regional cooling, behavioral rules, and lower-dose pegylated liposomal doxorubicin (PLD), in patients with gynecologic malignancies.

Intervention Characteristics/Basic Study Process:

PLD doses ranged from 30 to 50 mg/m2 every 21 to 28 days. All patients received premedication with oral dexamethasone 8 mg (12 hours before PLD) and pyridoxine 300 mg PO daily. All patients were advised to follow strict behavioral rules: keep skin well hydrated, avoid sunlight, minimize trauma to the hands and feet, avoid contact with warm water, and avoid hot foods and liquids. Patients who were enrolled from 2001 to December 2003 were in the non–regional cooling group (n = 25), whereas patients who were enrolled from January 2004 to 2006 were in the regional cooling group (n = 28). Patients received regional cooling (application of ice packs around wrists and ankles) and icicles during PLD infusion.

Sample Characteristics:

  • The study reported on a sample of patients who received PLD as a single therapy (n = 33), PLD plus carboplatin (n = 17), or PLD plus paclitaxel (n = 3).
  • All patients were women with gynecologic cancers (N = 53).

Setting:

Obstetrical/Gynecological Department at San Raffaele Hospital in Milan, Italy

Study Design:

This was a prospective, observational, single-center, nonrandomized study.

Measurement Instruments/Methods:

Skin toxicity was graded according to National Cancer Institute (NCI) and Gynecologic Oncology Group (GOG) criteria.

Results:

The incidence of PPE was significantly higher in the non–regional cooling group (n = 9, 36%) compared to the regional cooling group (n = 2, 7%; p = 0.0097).

Conclusions:

Multivariant analysis revealed the use of a regional cooling protocol and lower PLD dosage were significant factors in reducing the onset and incidence of PPE. The authors estimated the probability of developing PPE in a patient who receives 30 to 35 mg/m2 of PLD and follows the regional cooling protocol is 1.42%. Conversely, a patient who does not adapt this regional cooling protocol and receives 40 to 50 mg/m2 of PLD every three weeks has a 60.41% estimated probability of developing PPE.

Limitations:

  • The sample size was small.
  • This was a prospective, observational, nonrandomized study. Efficacy needs to be proven in a controlled and randomized study.
  • A combination of interventions was used in this study. All patients were given oral dexamethasone and oral pyridoxine as premedication. Therefore, determining the effectiveness of the individual interventions is difficult.

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