A healthcare professional’s guide to managing skin toxicities during EGFR-inhibitor therapy What to expect from EGFR-inhibitor therapy The goal of EGFR-inhibitor therapy is to interrupt the growth and spread of tumor cells by disrupting the signals sent from the epidermal growth factor receptor (EGFR), which is found on the surface of some cancer cells. Because EGFR is also present on many normal cells in the body, including skin cells, dermatologic toxicity occurs in up to 90% of patients undergoing treatment.1 In its mild-to-moderate state, skin toxicity can cause physical pain and discomfort and take an emotional toll on patients.2 For some patients, side effects can be serious and lead to life-threatening complications. In severe cases, the EGFR-inhibitor dose may be reduced, interrupted, or discontinued.1 While there are currently no guidelines based on large, randomized clinical trials for the management of EGFR-inhibitor–related dermatologic toxicities, you play a key role in educating patients and families on treatment side effects, advising about appropriate interventions, and offering emotional support.1 Teaching patients how to recognize and manage treatment-related side effects, along with early intervention by healthcare professionals, is a necessary component of the overall treatment plan.3 3 Skin toxicity and EGFR inhibitors Because EGFR is found on normal skin cells as well as certain cancer cells, treatment with an EGFR inhibitor may cause skin changes.3 Dermatologic side effects may include the following1: • Papulopustular rash (acne-like) • Paronychia (irritation at the sides of the fingernails or toenails) • Xerosis (dry skin) • Pruritus (itching) • Fissuring (cracking) • Photosensitivity Other common side effects of EGFR-inhibitor therapy include3-5: • Diarrhea • Fatigue • Ocular toxicity • Inflammation of the mouth, throat, or stomach • Hypomagnesemia • Abdominal pain • Nausea 4 Why do patients receiving EGFR-inhibitor therapy develop skin toxicity? Effects of EGFR inhibition in the skin6 Stratum corneum Stratum corneum Stratum corneum Epidermis Epidermis Epidermis Epidermi EGFR Dermis Stratum corneum EGFR EGFR inhibitor Dermis Blood vesselBlood vessel • EGFR is activated when specific ligands bind to receptors on the surface of the cell. By blocking the binding site of these receptors, EGFR inhibitors prevent cells from receiving these signals involved in cell growth and division6 EGFR inhibitor Dermis Dermis Neutrophils Neutrophils Blood vesselBlood ve Lymphocytes Lymphocytes • When EGFR inhibitors block the receptors on cancer cells, they are also believed to bind to receptor sites on skin cells. This binding is hypothesized to lead to cell-growth arrest and cell death, which can cause an inflammatory response that leads to tissue damage and consequent decrease in epidermal thickness, resulting in dermatologic toxicities6 Adapted from Lacouture ME. Nat Rev Cancer. 2006;6:803-812. 5 Skin rash: The most common side effect of EGFR-inhibitor therapy Skin rash occurs in up to 90% of patients undergoing treatment with an EGFR inhibitor. It is important to keep in mind that skin toxicity associated with EGFR-inhibitor therapy can be serious and potentially life threatening. Therefore, appropriate counseling and medical management is important when caring for patients treated with EGFR inhibitors.1,3 • Rash related to EGFR-inhibitor therapy typically appears within the first 2 weeks of treatment but may occur at any time3 – Most cases are mild or moderate but some cases may be severe – Usually occurs on the face, neck, or trunk2 – May change in intensity (improve or worsen) throughout the course of treatment3 – Usually resolves within 1 to 3 months after treatment is stopped1,3 • The rash may look like acne but is not2 – Pustular (flat) or papular (raised) lesions are present3 – Comedones (blackheads or whiteheads) are not usually associated with this rash2 • Secondary infections may occur2 – May produce yellowish crusting over lesions2 6 What to look for The following photographs provide examples of rash and nail changes. Erythema7 • Usually appears on the face, neck, or upper torso Papules/Pustules7 • Often contain pus and are accompanied by dry skin and pruritus Honey-yellow crusting2 • Y ellowish-brown crust overlying inflammatory eruptions with oozing of fluid from lesions, which may be indicative of a secondary bacterial infection Images above: Data on file, Amgen. Nail changes 7 • Lateral reddening and inflammation (paronychia) • Granulation tissue and pyogenic granulomas, accompanied by seropurulent discharge Reprinted with permission, from Mitchell EP, Perez-Soler R, Van Cutsem E, et al: Oncology. 21(11):4-9, 2007. 7 Counseling patients regarding skin toxicity when initiating EGFR-inhibitor therapy Healthcare professionals play a key role in teaching patients how to recognize and manage skin toxicities as well as in educating patients about the importance of early intervention. Patients should be advised to seek medical attention at the first sign of the development of any symptoms of skin toxicity.3 At the onset of EGFR-inhibitor therapy, patients should consider the following: Skin Care For Skin Rash • Make liberal use of nonirritating (free of perfumes or dyes) moisturizer to relieve or reduce dryness3 • Topical or oral antibiotics may be used for papules or pustules9 • void skin care products that contain A alcohol or other harsh additives and detergents or other household cleaning products8 • Oral and/or topical antihistamines may relieve itching7,9 • Use sunscreen with SPF 30 or higher2 • OTC acne preparations are not recommended due to their potential to exacerbate dryness and peeling7 • Wear clothing that limits sun exposure, particularly hats and long sleeves3 • Liquid bandages may be useful for skin fissures3 Sun Exposure 8 • Use of creams and lotions may exacerbate dry skin; limit use of gels to isolated/scattered papules and pustules9 Nail Care For Nail Changes • Avoid nail trauma to reduce the possibility of painful nail damage7 – Avoid pushing back cuticles or biting fingernails8,10 • Symptomatic relief may be achieved with the use of antiseptic soaks and by cushioning the affected area(s)3 – Avoid wearing tight shoes as they can exacerbate toenail changes10 – Do not use artificial nails as their materials can trap bacteria and fungus, increasing the risk of infection10 • Clip nails short and moisturize with lotions8,10 • Protect hands from excessive water by using rubber or cotton-lined gloves during such activities as washing dishes, gardening, or cleaning8 • Topical corticosteroids can reduce redness and treat severe lesions7 • Liquid bandages can be beneficial for nail fissuring3 • Silver nitrate may be helpful for pyogenic granuloma-like lesions11 • Topical and/or oral antibiotics may be used to treat bacterial superinfections3 Early intervention is important3 Treatment should be started at the first sign of skin or nail changes. Usually when a rash develops, patients can stay on therapy. However, depending on the severity of these changes, the EGFR-inhibitor dose may be reduced, interrupted, or discontinued. In addition to early intervention, communication among oncologists, nurses, dermatologists, and patients is important. 9 Your role is key Coping with EGFR-related skin toxicities can be difficult for patients. This side effect can cause significant appearance changes, pain, and in rare cases may be life threatening. Your role as a healthcare provider is vital when managing patients treated with EGFR-inhibitor therapy. Educate your patients about the importance of contacting their medical team at the first sign of any skin or nail changes. Establishing an open dialogue with your patients may allow for early intervention that may reduce the severity of rash and help relieve the burden of side effects. 10 Contact your Amgen representatives to request more information or materials. If you have any other questions, you may contact Amgen Medical Information at 1-800-77-AMGEN (1-800-772-6436). References: 1. Lynch TJ Jr, Kim ES, Eaby B, Garey J, West DP, Lacouture ME. Oncologist. 2007;12:610-621. 2. Pérez-Soler R, Delord JP, Halpern A, et al. Oncologist. 2005;10:345-356. 3. Sipples R. Semin Oncol Nurs. 2006;22:28-34. 4. Weber J, McCormack PL. Biodrugs. 2008;22:403-411. 5. Krozely P. Clin J Oncol Nurs. 2004;8:163-168. 6. Lacouture ME. Nat Rev Cancer. 2006;6:803-812. 7. Dick SE, Crawford GH. Commun Oncol. 2005;2:492-496. 8. Eaby B, Culkin A, Lacouture ME. Clin J Oncol Nurs. 2008;12:283-290. 9. Rhee J, Oishi K, Garey J, Kim E. Clin Colorectal Cancer. 2005;5(suppl 2):S101-S106. 10. Fleishman SB, Fox LP, Garfield DH, Viele CS, Messner C. Cancercare Web site. www.cancercare.org/pdf/booklets /ccc_managing_rash.pdf. Accessed September 10, 2009. 11. Segaert S. Target Oncol. 2008;3:245-251. ©2010 Amgen Inc. All rights reserved. 47636 11-09 P42275