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EGFR Pathway

EGFR Pathway

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EGFR Pathway

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  1. EGFR Pathway • EGFR, also termed HER1 • Regulates cell division, repair, survival1 • Likely involved in tumor metastasis1 • Contains an intracellular tyrosine kinase (TK) domain1 • Overexpressed in tumors but in low levels on normal cells1 • EGFR inhibitors inhibit intracellular phosphorylation of TK at these receptors2 1. Huang S-M, et al. Invest New Drugs. 1999;17:259-269. 2. Tarceva (erlotinib). Package insert. Seymour, IN: Schwarz Pharma Manufacturing; 2007.

  2. Skin Rash Associated with EGFR Inhibitors • A common toxicity associated with EGFR inhibitors1,2 • Avoid sun, heat, and humidity; sunscreen may help prevent rash2 • Use mild soaps, and keep skin moisturized2,3 • Water-based makeup is well tolerated and can conceal rash2,3 • Topical retinoids: not recommended; may worsen rash2,3 • Topical steroids: consider for moderate rash 1. Clark GM, et al. 39th ASCO; May 31-June 3, 2003. Abstract 786. 2. Pérez-Soler R, et al. Oncologist. 2005;10:345-356. 3. Shah NT, et al. J Clin Oncol. 2005;23;165-174.

  3. Tips for Managing Rash Associated with EGFR Inhibitors • For itching: • Cool compresses; Aveeno® • Clindamycin gel • Diphenhydramine cream or gel • Diphenhydramine oral • Hydroxyzine hydrochloride • For cracked skin or cuticles: • Bag Balm®, tea tree oil, jojoba oil, Scalpicin® for scalp lesions, white cotton gloves for hand lesions • For wound care: • Regenecare® • Mild soap: Neutrogena products, Dove®, Aveeno®, Basis® • Moisturizers: Neutrogena® cream, Eucerin®, Vaseline Intensive Care®, Curél®, jojoba moisturizer, Cetaphil® • Vaginal lubricants: K-Y® jelly, Astroglide® • Antidandruff products containing selenium

  4. Nursing Management of Skin Rashes in Targeted Therapy • Assess all skin surfaces • Document appearance of rash (eg, color, size, additional descriptions) • Document areas affected by rash • Document any secondary infections • Document response to previous interventions, including physical assessment and patient subjective report

  5. Infected Skin Rash • When to suspect • Yellow/brown crust over skin lesions • Pus oozing from skin lesions • Abrupt change in appearance of skin lesions • Start topical or oral antibiotics at 1st suspicion • Clindamycin: 300 mg PO TID • Clindamycin lotion or gel: 10 mg/cc topically BID • Tetracycline: 500 mg PO BID • Minocycline: 100 mg PO BID • Doxycycline: 100 mg PO BID • Ulcerative lesions: barrier protection • Petroleum jelly • Silver sulfadiazine ointment

  6. VEGF receptors Found primarily on endothelial cells1 Receptor is transmembrane TK2 TK transmits signals from receptor to cell nucleus2 Bevacizumab prevents VEGF from binding to its receptors and inhibits VEGF-induced angiogenesis3 VEGF Receptors Angiogenesis Lymphangiogenesis 1. Nagy JA, et al. J Exp Med. 2002;196:1497-1506. 2. Dvorak HF, et al. Am J Pathol. 1995;146:1029-1039. 3. Avastin (bevacizumab). Package insert. South San Francisco, CA: Genentech, Inc; 2008.

  7. BevacizumabWound-Healing Complications • Wound-healing complications, including wound dehiscence • In some instances resulting in fatality • Permanently discontinue bevacizumab in patients with wound dehiscence requiring intervention • Exact safe interval between surgery and initiation of bevacizumab not known • Recommend >28 days Avastin (bevacizumab). Package insert. South San Francisco, CA: Genentech, Inc; 2008.

  8. BevacizumabHemoptysis and Bleeding • Hemoptysis reported in patients with NSCLC treated with chemotherapy and bevacizumab • Serious or fatal hemoptysis in 31% of patients with squamous histology and 4% with nonsquamous histology1 • Patients with CNS metastases or large tumors located near large arteries may be at increased risk for life-threatening bleeding while receiving bevacizumab1 • Grade 1 epistaxis is most common • Patients with recent hemoptysis should not receive bevacizumab1 • Bevacizumab should be used with caution in patients with known coagulation disorders2 • Low-dose warfarin has not been associated with increased risk of serious bleeding1 • Educate patients about signs and symptoms of bleeding 1. Avastin (bevacizumab). Package insert. South San Francisco, CA: Genentech, Inc; 2008. 2. Hurwitz H, et al. Semin Oncol. 2006;33:S26-S34.

  9. BevacizumabArterial Embolic Events • Warning of serious and fatal arterial thromboembolic events • Approximate 2-fold increased risk, estimated overall risk: 5% • Risk factors • History of arterial thromboembolism prior to bevacizumab therapy • Age: >65 years • Prior exposure to bevacizumab • Recommend permanently discontinuing bevacizumab in anyone experiencing myocardial infarction, transient ischemic attack, or angina Avastin (bevacizumab). Package insert. South San Francisco, CA: Genentech, Inc; 2008.

  10. Nursing Management Toxicities in Targeted Therapy • Patient assessment and monitoring for specific toxicities (eg, cardiotoxicities) would be improved with evidence-based guidelines for frequency and type of monitoring tests • Need to follow patients over time to evaluate long-term complications of targeted therapy • Careful patient education needed to explain signs and symptoms, associated risks, and potential interventions related to targeted therapy