OPTIMIZING MANAGEMENT OF RASH ASSOCIATED WITH EGFR INHIBITORS:

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1 OPTIMIZING MANAGEMENT OF RASH ASSOCIATED WITH EGFR INHIBITORS: A WORKSHOP FOR ONCOLOGY NURSES C ONTINUING E DUCATION R EGIONAL S YMPOSIUM F OR O NCOLOGY N URSES Sponsored by: This activity is supported by an independent educational grant from Bristol-Myers Squibb Company and ImClone Systems Incorporated.

2 ACCREDITATION INFORMATION TARGET AUDIENCE This activity has been designed to meet the educational needs of patient care oncology nurses and advanced practice oncology nurses. PURPOSE To educate nurses on effective strategies for the assessment and management of dermatologic toxicities related to treatment with epidermal growth factor receptor (EGFR) inhibitors. PROGRAM OVERVIEW This presentation will review the management of rash experienced by patients receiving the novel class of agents that target EGFR. Although generally well tolerated, EGFR inhibitors are associated with dermatologic reactions in most patients yet no evidence-based management guidelines have been established. In this regional CE program, oncology nurse experts will provide thorough answers to oncology nurses most pressing questions related to the administration of EGFR inhibitors in clinical practice. The pathophysiology of cellular signaling pathways involved in EGFR inhibition and mechanisms of action of EGFR inhibitors will be presented in 3-D video animation. Thought leaders will review the clinical application and ongoing investigations of agents, and provide a comprehensive review of rash assessment and management. Case presentations will be used to support key learning objectives. At the commencement of each program, nurses will be encouraged to participate in a survey regarding experiences with rash assessment tools and management. The results of the survey will be collated, and will specifically evaluate variations in assessment and management based on demographics and practice setting. Results will highlight knowledge gaps and provide direction for subsequent CE programs. LEARNING OBJECTIVES Upon completion of this program, participants should be better able to: Describe the mechanism of action of EGFR inhibitors Identify current clinical applications for EGFR inhibitors Describe the side-effect profiles of EGFR inhibitors Recall appropriate nursing assessment and management of rash experienced by patients receiving EGFR inhibitor therapy CHAIRPERSON Karen J. Oishi, MSN, NP-C, OCN The University of Texas M. D. Anderson Cancer Center ACCREDITATION STATEMENTS This educational activity for 1.0 contact hour will be provided by IMER. IMER is an approved provider of continuing education by the Georgia Nurses Association, an accredited approver by the American Nurses Credentialing Center s Commission on Accreditation. IMER is approved by the California Board of Registered Nursing, Provider Number for 1.2 contact hours. This program has been approved for 1.0 contact hours of continuing education (which includes 0.5 hours of pharmacology) by the American Academy of Nurse Practitioners. Application pending approval with the American Academy of Nurse Practitioners (including pharmacology hours). A statement of credit will be issued only upon receipt of a completed activity evaluation form DISCLOSURE OF UNLABELED USE IMER requires instructors, planners, managers, and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by IMER for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations. DISCLAIMER Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients conditions and possible contraindications on dangers in use, review of any applicable manufacturer s product information, and comparison with recommendations of other authorities. SAFEGUARDS AGAINST COMMERCIAL BIAS IMER affirms that the content and format of its CE activities and related materials promote improvements and quality in healthcare and do not promote a specific proprietary business interest of a commercial entity. To this end, IMER employs several strategies to ensure the absence of commercial bias, including but not limited to review of all planned content for CE activities sponsored by IMER to ensure adherence to the American Nurses Credentialing Center s criteria and operational requirements and the Accreditation Council for Continuing Medical Education s content validation statements and resolution of any actual or perceived conflict of interest that exist. We employ three metrics as we review materials: 1. Fair balance a. Recommendations or emphasis must fairly represent and be based on a reasonable and valid interpretation of the information available on the subject matter b. No single product or service is overrepresented when other equal competing products or services are available for inclusion 2. Scientific objectivity of studies mentioned in the materials

3 OPTIMIZING MANAGEMENT OF RASH ASSOCIATED WITH EGFR INHIBITORS: A WORKSHOP FOR ONCOLOGY NURSES CONTINUING EDUCATION REGIONAL SYMPOSIUM FOR ONCOLOGY NURSES TABLE OF CONTENTS 02 Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses Appendices 21 Appendix A. Pharmaceutical Glossary 22 Appendix B. EGFR Rash Product List 12/31/2008 Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses 1

4 OPTIMIZING MANAGEMENT OF RASH ASSOCIATED WITH EGFR INHIBITORS: A WORKSHOP FOR ONCOLOGY NURSES Karen J. Oishi, MSN, NP-C, OCN The epidermal growth factor receptor (EGFR) plays a critical role in the cell regulation pathway. In the epidermis, EGFR stimulates epidermal growth, inhibits differentiation, inhibits inflammation, and accelerates wound healing. In malignant cells, EGFR is overexpressed, which leads to cell proliferation, angiogenesis, metastasis, and inhibition of apoptosis. EGFR inhibitors are increasingly being used in the treatment of solid tumors of various types. This class of agents is associated with cutaneous reactions of varying severity that could lead to interruption of optimal dosing. No evidence-based management guidelines have been established for these dermatologic toxicities, however management algorithms are emerging. Nurses should be aware of the latest assessment and management tools used for EGFR inhibitors in order to prolong survival while maintaining quality of life. 2 Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses

5 Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses Objectives Describe the mechanism of action of EGFR inhibitors Identify clinical applications for EGFR inhibitors Describe the side-effect profiles of available EGFR inhibitors Discuss appropriate nursing assessment of rash experienced by patients receiving EGFR inhibitor therapy Discuss potential treatment strategies to manage EGFR rash EGFR = epidermal growth factor receptor. Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses 3

6 The Role of EGFR Inhibitors EGFR is critical in the cell regulation pathway Three important components Extracellular ligand-binding domain Transmembrane domain Intracellular domain (tyrosine kinase activity) In malignant cells, EGFR is overexpressed and malfunctions can lead to Inhibition of apoptosis Invasion Metastasis Release of VEGF VEGF = vascular endothelial growth factor. Ritter & Arteaga, EGFR Inhibitors: FDA Indications EGFR-TKIs Causes rash and diarrhea FDA approved medications include Erlotinib: Approved November 2004 Gefitinib: Approved May 2003 Lapatinib: Approved March 2007 EGFR-MoAbs Causes rash and hypomagnesemia FDA approved medications include Cetuximab: Approved February 2004 Panitumumab: Approved September 2006 TKI = tyrosine kinase inhibitor; MoAbs = monoclonal antibodies. Vectibix (prescribing information), 2007; Tarceva (prescribing information), 2008; Iressa (prescribing information), 2005; Tykerb (prescribing information), 2008; Erbitux (prescribing information), Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses

7 Clinical Trials Drug Phase Disease Cetuximab III (FLEX) NSCLC Erlotinib I/II II SCCHN Breast ZD6474 (vandetinib) Sorafenib Sunitinib III II II/III ESCAPE II II/III II NSCLC Breast NSCLC Renal cell NSCLC Hepatocellular Gefitinib II Ovarian NSCLC = non-small cell lung cancer; SCCHN = squamous cell carcinoma of the head and neck. Pirker et al, 2008; Vermorken et al, 2005; Herchenhorn et al, 2006; Kim et al, 2007; Natale, 2008; Scagliotti et al, 2008; Scagliotti et al, 2007; Govindan et al, 2008; Pautier et al, 2007; Zhu et al, 2008; Amato et al, EGFR Inhibitors Agent Pharmaceutical Class Description Cetuximab* Chimeric MoAb EGFR-MoAbs Panitumumab* Human MoAb EGFR-MoAbs ICR 62 Murine MoAb EGFR-MoAbs Erlotinib* Quinazoline EGFR-TKI Gefitinib* Quinazoline EGFR-TKI PD Quinazoline EGFR-TKI PKI-166 Pyridopyrimidine EGFR-TKI/HER2 PD Pyridopyrimidine EGFR-TKI Lapatinib* Quinazoline EGFR-TKI/HER2 * U.S. FDA Approved Mendelsohn & Baselga, 2003; Harari, Allen, & Bonner, 2007; Sridhar, Seymour, & Shepherd, 2003; Bos et al, Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses 5

8 Cutaneous Adverse Events Rash Nonrash Xeroderma Xerosis Pruritis Paronychia Alopecia Hypertrichosis Trichomegaly Ocular changes Hypersensitivity reactions Mucositis Leukocytoplastic vasculitis Basti, 2007; Morse & Calarese, 2006; Dick & Crawford, 2005; Boeck, Wollenberg, & Heinemann, 2007; Lenz, Drug Incidence of Rash Incidence of Rash (%) Incidence of Rash (%) All grades Grade 3 4 No. of Pts Reference Gefinitib (250 mg/d) Herbst et al, 2004 Erlotinib (150 mg/d) Erlotinib (100 mg) + Gemcitabine Cetuximab + XRT (HNC) Cetuximab + irinotecan (CRC) Cetuximab (CRC) Shepherd et al, 2005 Tarceva (prescribing information), 2008 Bonner et al, 2006 Erbitux (prescribing information), 2007 Erbitux (prescribing information), 2007 Panitumumab 90 < Van Cutsem, Peeters, et al, 2007 Lapatinib 44 < Ravaud et al, 2006 XRT = radiation; HNC = head and neck cancer; CRC = colorectal cancer. 6 Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses

9 Clinical Course of Rash TKIs BSA = body surface area. Oishi, Starts within 8 10 days of therapy MoAbs Seen within 1 2 weeks Peaks in 3 weeks Rash may appear between Days 1 14 Generally covers < 50% BSA May be intermittent Usually mild or moderate Caudal Can affect the face, neck, scalp, and upper thorax Appearance of Rash Macular, papular, and pustular Rash caused by EGFR-MoAbs (eg, cetuximab, panitumumab) tend to be more papulopustular and generalized The face, scalp, upper chest/neck, and upper back are rich with sebaceous glands and susceptible to photoexposure Oishi, Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses 7

10 Grading Systems for Rash ECOG NCI v.3 Criteria Busam et al, 2001 Grade Rash/desquamation Rash/desquamation Rash/desquamation 1 Scattered macular/papular eruption or erythema that is asymptomatic 2 Scattered macular/papular eruption or erythema with pruritus or other associated symptoms Macular/papular eruption or erythema without associated symptoms Macular/papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering < 50% of BSA Asymptomatic macular/ papular erythematous eruption in an acneiform distribution Same as grade 1 plus symptoms such as pruritus 3 Generalized symptomatic macular, papular, or vesicular eruption 4 Exfoliative dermatitis or ulcerating dermatitis Severe, generalized erythroderma, or macular/ papular/vesicular eruption; desquamation covering 50% BSA Generalized exfoliative, ulcerative, or bullous dermatitis Extension of the eruption beyond the acneiform distribution of the head, chest, and back or the development of painful lesions or minor ulceration Exfoliative or ulcerating dermatitis ECOG = Eastern Cooperative Oncology Group; NCI = National Cancer Institute. Busam et al, 2001; Oishi, Proposed EGFR Grading System Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0 Categories Relevant to HER1/EGFR-Associated Rash Mild Moderate Severe Grade 1 Grade 2 Grade 3 Grade 4 Rash characteristics Macular/ papular eruption or erythema without associated symptoms (no impact on daily activities) Macular/papular eruption or erythema with pruritus or other mild associated symptoms; localized desquamation or other lesions covering < 50% of BSA (minimal impact on daily activities) Severe, generalized erythema, severe associated symptoms, macular/papular/ vesicular eruption; desquamation covering 50% BSA (significant impact on daily activities) Generalized exfoliative, ulcerative, or bullous dermatitis National Cancer Institute, 2006; Lynch et al, Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses

11 Etiology of Rash Unclear Inhibition of EGFR-TKI/MoAbs activity Histology EGFR expressed in the epidermal/dermal layers Inflammatory process from dysregulated keratinocyte proliferation in epidermal layer Infiltration of neutrophils within the dermal layer is seen from rash skin biopsies Grading Subjective versus objective Saltz et al, 2001; Perez-Soler et al, 2005; Oishi, Clinical Marker of Response There is a correlation between rash and survival in all EGFR inhibitors across tumors NSCLC Grade 0 = 1.5 mos Grade 1 = 8.5 mos Grade 2 3 = 19.6 mos MCRC Grade 0 = 1.7 mos Grade 1 = 4.9 mos Grade 2 3 = 9.4 mos It is important to treat rash and maintain patients on therapy Increasing the drug dose until skin toxicity appears is being studied MCRC = metastatic colorectal cancer. Perez-Soler & Saltz, 2005; Van Cutsem, Humblet, et al, 2007; Lenz et al, Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses 9

12 Clinical Approaches Goals To maintain quality of life by minimizing symptoms of discomfort and improving appearance Keep patients on clinically effective dose Pharmacologic CYP3A4 inhibitors and inducers Nonpharmacologic Erlotinib: Take 1 hour before or 2 hours after food Gefitinib: Take with or without food Lapatinib: Take 1 hour before or 1 hour after a meal Oishi, 2008; Iressa (prescribing information), 2005; Tykerb (prescribing information), Proactive Management General measures Sunscreen (SPF 30) that contains zinc oxide or titanium dioxide The use of mild soap and shampoo Emollients Thick Alcohol free Perfume free Dye free Make-up Hypoallergenic No topical retinoids, vitamin D analogs, or benzoyl peroxide Oishi, 2008; Lacouture, Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses

13 Proactive Management (cont.) Medications Lidocaine OTC (hydrocortisone 1%) Prescription (hydrocortisone 2.5%, clindamycin gel 1%) Tetracycline, minocycline, doxycycline, sulfamethoxazole, trimethoprim, pimecrolimus, and mupirocin Oishi, 2008; Lacouture, Example of a Treatment Algorithm Grade Macular Rash Papular or Pustular Rash Grade 1 Grade 2 Grade 3/4 (dermatology consult considered) Hydrocortisone topical cream/lotion (OTC 1%) Fluticasone propionate topical steroid bid if limited to < 2 body areas, if > 2 body areas, consider oral methylprednisolone Oral methylprednisolone Clindamycin gel for isolated scattered lesions; clindamycin lotion for multiple scattered areas Oral antibiotics: Minocycline hydrochloride 200 mg bid Day 1 then 100 mg bid OR trimethoprim/ sulfamethoxazole bid Oral antibiotics: Minocycline hydrochloride 200 mg bid Day 1 then 100 mg bid OR trimethoprim/ sulfamethoxazole bid Dry Skin Pruritus Ulcerative Lesions N/A N/A N/A Perfume-, alcohol-, dyefree lotion applied bid Perfume-, alcohol-, dyefree lotion applied bid Topical antihistamine or oral diphenydramine mg q 6 hrs prn OR hydroxyzine hydrochloride mg po q 6hrs prn Oral diphenhydramine mg q 6hrs prn OR hydroxyzine hydrochloride mg po q 6 hrs prn N/A Silver sulfadiazine ointment (1% qd or bid) Oishi, Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses 11

14 Lynch Treatment Algorithm Mild Continue EGFR inhibitor at current dose and monitor for change in severity No treatment or Topical hydrocortisone 1% or 2.5% cream and/or clindamycin 1% gel Reassess after 2 weeks; if reactions do not improve, proceed to next step Moderate Continue EGFR inhibitor at current dose and monitor for change in severity; continue treatment of skin reaction Hydrocortisone 2.5% cream or clindamycin 1% gel or pimecrolimus 1% cream plus doxycycline 100 mg bid or minocycline 100 mg bid Reassess after 2 weeks; if reactions do not improve, proceed to next step Severe Reduce EGFR inhibitor dose per label and monitor for change in severity; continue treatment of skin reaction Treat as above, plus methylprednisolone dose pack Reassess after 2 weeks; if reactions worsen, dose interruption or discontinuation may be necessary Lynch et al, SERIES Clinic Skin and eye reactions to inhibitors of EGFR and kinases (SERIES) clinic Mild/moderate Start doxycycline or minocycline 50 mg bid/ pimecrolimus bid Severe Start doxycycline or minocycline 100 mg bid/ pimecrolimus bid Then gradually increase the doses PRN Add oral steroids if not improved Lacouture et al, Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses

15 Dose Modification for Erlotinib Erlotinib 150 mg ( grade 3 dermatologic toxicities) Restart at 150 mg with prophylactic measures Still grade 3 4, restart at 100 mg with prophylactic measures Still grade 3 4, restart at 50 mg with prophylactic measures If rash continues to grade 3 4, stop therapy Tarceva (prescribing information), Dose Modification for Cetuximab Cetuximab 250 mg/m 2 ( grade 3 dermatologic toxicities) 1 2 week treatment delay Restart at 250 mg/m 2 with prophylactic measures Still grade 3 4, restart at 200 mg/m 2 with measures Still grade 3 4, restart at 150 mg/m 2 with measures If rash continues to grade 3 4, consider discontinuation Erbitux (prescribing information), Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses 13

16 Dose Modification for Lapatinib Lapatinib 1,250 mg/m 2 ( grade 2 dermatologic toxicities) Discontinue treatment until toxicity improves to grade 1 or less Restart at 1,250 mg/day If toxicity recurs, lower dose to 1,000 mg/day If severe toxicities persist, discontinue treatment Tykerb (prescribing information), Dose Modification for Panitumumab Panitumumab 6 mg/kg ( grade 3 dermatologic toxicities) Withhold until grade 2, resume at 50% of original dose Increase by increments of 25% of original dose until 6 mg/kg is reached if no further toxicities occur If no improvement within 1 month or if toxicities recur, permanently discontinue Vectibix (prescribing information), Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses

17 Scope Recent Trials Prophylactic ability of either oral minocycline or topical tazarotene to reduce or prevent cetuximab-related acneiform rash when administered starting on Day 1 of cetuximab therapy Jatoi Tetracycline may reduce the severity of rashes associated with EGFR inhibitors Scope et al, 2007; Jatoi et al, Impact on Quality of Life Psychosocial implications Cosmetic effect Functional assessment of side effects to therapy (FAST) Development of a self report questionnaire to assess dermatology-related quality of life in patients treated with EGFR inhibitors Physical symptoms impact HRQL HRQL = health-related quality of life. Wagner et al, Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses 15

18 Be proactive Early intervention Key Takeaways Prescriptions prior to starting therapy (topical hydrocortisone and clindamycin) Education and counseling sessions Follow-ups Dermatology consult considered PRN 16 Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses

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22 REFERENCES Amato RJ, Jac J, Harris P, et al (2008). A phase II trial of intra-patient dose escalated sorafenib in patients with metastatic renal cell cancer. J Clin Oncol, Proc Am Soc Clin Oncol, 26(May 20 suppl), Abstract Basti S (2007). Ocular toxicities of epidermal growth factor receptor inhibitors and their management. Cancer Nurs, 30(4), Boeck S, Wollenberg A, & Heinemann V (2007). Leukocytoclastic vasculitis during treatment with the oral EGFR tyrosine kinase inhibitor erlotinib. Ann Oncol, 18(9), Bonner JA, Harari PM, Giralt J, et al (2006). Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med, 354(6), Bos M, Mendelsohn J, Kim YK, et al (1997). PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent manner. Clin Cancer Res, 3(11), Busam KJ, Capodieci P, Motzer R, et al (2001). Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Br J Dermatol, 144(6), Dick SE, & Crawford GH (2005). Managing cutaneous side-effects of epidermal growth factor receptor inhibitors. Community Oncol, 2(6), Erbitux (prescribing information). Princeton, NJ: Bristol-Myers Squibb Company; Govindan R, Blumenschein G, Groen HJM, et al (2008). Sunitinib plus erlotinib, a novel VEGFR-EGFR co-inhibition treatment strategy in patients with metastatic non-small cell lung cancer. J Thorac Oncol, 3(4 suppl 1), Abstract 216P. Harari PM, Allen GW, & Bonner JA (2007). Biology of interactions: Antiepidermal growth factor receptor agents. J Clin Oncol, 25(26), Herbst RS, Giaccone G, Schiller JH, et al (2004). Gefitinib in combination with paclitaxel and carboplatin in advanced non-small cell lung cancer: A phase III trial INTACT 2. J Clin Oncol, 22(5), Herchenhorn D, Dias FL, Ferreira CG, et al (2006). Phase I/II study of erlotinib combined with cisplatin and radiotherapy for locally advanced squamous cell carcinoma of the head and neck. J Clin Oncol, Proc Am Soc Clin Oncol, 24(18S; June 20 suppl), Abstract Iressa (prescribing information). Wilmington, DE: AstraZeneca Pharmaceuticals LP; Jatoi A, Rowland K, Sloan JA, et al (2007). Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes. Cancer, 113(4), Kim ES, Kies MS, Glisson BS, et al (2007). Final results of a phase II study of erlotinib, docetaxel, and cisplatin in patients with recurrent/metastatic head and neck cancer. J Clin Oncol, Proc Am Soc Clin Oncol, 25(18S; June 20 suppl), Abstract Lacouture ME (2006). Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer, 6(10), Lacouture ME, Basti S, Patel J, et al (2006). The SERIES clinic: An interdisciplinary approach to the management of toxicities of EGFR inhibitors. J Support Oncol, 4(5), Lenz HJ (2007). Management and preparedness for infusion and hypersensitivity reactions. Oncologist, 12(5), Lenz HJ, Van Cutsem E, Khambata-Ford S, et al (2006). Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol, 24(30), Lynch TJ, Kim ES, Eaby B, et al (2007). Epidermal growth factor receptor inhibitor- associated cutaneous toxicities: An evolving paradigm in clinical management. Oncologist, 12(5), Mendelsohn J, & Baselga J (2003). Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol, 21(14), Morse L, & Calarese P (2006). EGFR-targeted therapy and related skin toxicity. Semin Oncol Nurs, 22(3), Natale RB (2008). Dual targeting of the vascular endothelial growth factor receptor and epidermal growth factor receptor pathways with vandetinib in patients with advanced or metastatic non-small cell lung cancer. J Thorac Oncol, 3(suppl 2), S128 S130. National Cancer Institute (2006). Common toxicity criteria for adverse events v.3.0 (CTCAE). Retrieved October 1, 2008 from Oishi K (2008). Clinical approaches to minimize rash associated with EGFR inhibitors. Oncol Nurs Forum, 35(1), Pautier P, Joly F, Kerbrat P, et al (2007). Gefitinib in combination with paclitaxel and carboplatin as second-line therapy for ovarian, tubal or peritoneal adenocarcinoma: Final results of a phase II study. J Clin Oncol, Proc Am Soc Clin Oncol, 25(18S; June 20 suppl), Abstract Perez-Soler R, Delord JP, Halpern A, et al (2005). HER1/EGFR inhibitorassociated rash: Future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum. Oncologist, 10(5), Perez-Soler R, & Saltz L (2005). Cutaneous adverse effects with HER1/EGFR-targeted agents: Is there a silver lining? J Clin Oncol, 23(22), Pirker R, Szczesna A, von Pawel J, et al (2008). FLEX: A randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine versus alone in the first-line treatment of patients with advanced non-small cell lung cancer. J Clin Oncol, 26(May 20 suppl), Abstract 3. Ravaud A, Hawkins R, Gardner J, et al (2006). Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: A randomized phase III clinical trial. J Clin Oncol, 26(14), Ritter CA, & Arteaga CL (2003). The epidermal growth factor receptor tyrosine kinase: A promising therapeutic target in solid tumors. Semin Oncol, 30(1 suppl 1), Saltz L, Rubin MS, Hochster H, et al (2001). Acne-like rash predicts response in patients treated with cetuximab plus irinotecan in CPT-11 refractory colorectal cancer that expresses epidermal growth factor receptor [Abstract]. Clin Cancer Res, 7, Abstract 3766s. Scagliotti G, Novella S, Brahmer J, et al (2007). A phase II study of continuous daily sunitinib dosing in patients with previously-treated advanced non-small cell lung cancer. J Thorac Oncol, 2(8 suppl 4), Abstract 275O. Scagliotti G, von Pawel J, Reck M, et al (2008). Sorafenib plus carboplatin/paclitaxel in chemonaive patients with stage IIIB-IV nonsmall cell lung cancer: Interim analysis results from the phase III, randomized, double-bline, placebo-controlled, ESCAPE trial. J Thorac Oncol, 3(4 suppl 1), Abstract PD Scope A, Agero AL, Dusza SW, et al (2007). Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol, 25(34), Shepherd FA, Pereira JR, Ciuleanu T, et al (2005). Erlotinib in previously treated non-small cell lung cancer. N Engl J Med, 353(2), Sridhar SS, Seymour L, & Shepherd F (2003). Inhibitors of epidermal growth factor receptors: A review of clinical research with a focus on non-small cell lung cancer. Lancet Oncol, 4(7), Tarceva (prescribing information). South San Francisco, CA: Genentech USA, Inc; Tykerb (prescribing information). Research Triangle Park, NC: GlaxoSmithKline; Van Cutsem E, Humblet Y, Gelderblom H, et al (2007). Cetuximab doseescalation study in patients with metastatic colorectal cancer with no or slight skin reactions on cetuximab standard dose treatment (EVER- EST): Pharmacokinetic and efficacy data of a randomized study [Abstract]. Proc Am Soc Clin Oncol, GI Cancers Symp, Abstract 237. Van Cutsem E, Peeters M, Siena S, et al (2007). Open label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy refractory metastatic colorectal cancer. J Clin Oncol, 25(13), Vectibix TM (prescribing information). Thousand Oaks, CA: Amgen Inc; Vermorken J, Bourhis J, Trigo J, et al (2005). Cetuximab in recurrent/ metastatic squamous cell carcinoma of the head and neck refractory to first-line platinum-based therapies. J Clin Oncol, Proc Am Soc Clin Oncol, 23(16S; June 1 suppl), Abstract Wagner L, Lai SE, Lorusso AP, et al (2007). Development of a functional assessment of side-effects to therapy questionnaire to assess dermatology-related quality of life in patients treated with EGFR inhibitors: The FAST-EGFRI. J Clin Oncol, Proc Am Soc Clin Oncol, 25(18S; June 20 suppl), Abstract Zhu AX, Sahani DV, di Tomaso E, et al (2008). Sunitinib monotherapy in patients with advanced hepatocellular carcinoma: Insights from a multidisciplinary phase II study. J Clin Oncol, 26(May 20 suppl), Abstract Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses

23 APPENDIX A. Pharmaceutical Glossary Generic Brand Name cetuximab Erbitux clindamycin Cleocin T ClindaMax doxycycline Doryx Monodox erlotinib Tarceva gefinitib Iressa gemcitabine Gemzar lapatinib Tykerb methylprednisolone Medrol minocycline Dynacin Minocin Generic Brand Name mupirocin Bactroban panitumumab Vectibix TM pimecrolimus Elidel sorafenib Nexavar sulfamethoxazole and trimethoprim Bactrim sunitinib Sutent tazarotene Tazorac tetracycline Achromycin Sumycin Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses 21

24 APPENDIX B. EGFR Rash Product List Side Effects of EGFR Inhibitors Cracked Cuticles Scalp Care Cracks/Fissures Erythema Itch/Pruritus Brand Name Bag Balm Head and Shoulders White cotton gloves Tea tree oil Joboba oil Scalpicin Hypoallergenic mild baby shampoo (except Baby Magic products) Band-Aid liquid bandages Bag Balm Zim s Crack Creme Baby diaper rash cream Cleocin Lindi cream T-gel Benadryl (oral or topical) Atarax Calamine lotion Oatmeal bath Suggestions Generic Name/Active Ingredient 8-hydroxyquinoline sulfate (0.3%) pyrithione zinc hydrocortisone (1%) sorbitan laurate liquid cyanoacrylate 8-hydroxyquinoline sulfate (0.3%) octinoxate (7.5% UVG) zinc oxide > 10% hydrocortisone (0.5% 1%) clindamycin gel 10 mg/cc bid astaxanthin extract salicylic acid or zinc pyrithione diphenhydramine hydroxyzine zinc oxide and iron oxide (0.5%) Recommendations for Patients on EGFR Inhibitors Avoid Sunlight Moisturizers Moisturizing Makeup Rash Soap/Cleansers Vaginal Lubrication Brand Name Sunscreens (> 30 SPF) Anthelios Vaseline Intensive Care Neutrogena Hand Cream Eucerin (Aquaphor ) Curel Cetaphil Jeans cream Lindi facial serum Dermablend Lindi facial serum Basis Dove Aveeno body wash Neutrogena Cetaphil Astroglide K-Y Jelly Suggestions Generic Name/Active Ingredient zinc oxide, titanium oxide mexoryl SX/XL petrolatum avobenzone homosalate glycerin glycerin tocopheryl acetate astaxanthin extract titanium oxide astaxanthin extract hydrocortisone (0.5% 1%) glycerin sodium lauroyl isethionate sodium trideceth sulfate salicylic acid (2%) glycerin, propylparaben glycerin, hydroxyethylcellulose Bush N, & Smith LH (2001). Hand-foot syndrome. Oncol Nurs Forum, 28, ; Fox LP (2006). Pathology and management of dermatologic toxicities associated with anti-egfr therapy. Oncology, 20(5 Suppl 2), 26 34; Lacouture ME, Wu S, Robert C, et al (2008). Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist, 13(9), ; Pérez-Soler R, Delord JP, Halpern A, et al (2005). HER1/EGFR inhibitor-associated rash: Future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum. Oncologist, 10(5), ; Viale PH, & Sommers R (2007). Nursing care of patients receiving chemotherapy for metastatic colorectal cancer: Implications of the treatment continuum concept. Semin Oncol Nurs, 23, Optimizing Management of Rash Associated With EGFR Inhibitors: A Workshop for Oncology Nurses

25 OPTIMIZING MANAGEMENT OF RASH ASSOCIATED WITH EGFR INHIBITORS: A WORKSHOP FOR ONCOLOGY NURSES C ONTINUING E DUCATION R EGIONAL S YMPOSIUM F OR O NCOLOGY N URSES DID YOUR ONCOLOGY NURSING COLLEAGUES MISS THIS EVENT? An archive of the live presentation for OPTIMIZING MANAGEMENT OF RASH ASSOCIATED WITH EGFR INHIBITORS: A WORKSHOP FOR ONCOLOGY NURSES will be posted on If you have questions about this event, them to 346Live@imeronline.com

26 2008 Institute for Medical Education & Research, Inc