Article

Clinical Approaches to Minimize Rash Associated With EGFR Inhibitors

Karen Oishi

epidermal growth factor, inhibitors, management
ONF 2008, 35(1), 103-111. DOI: 10.1188/08.ONF.103-111

Purpose/Objectives: To present a systematic approach for managing the skin rash associated with epidermal growth factor receptor (EGFR)-targeted therapies.

Data Sources: Clinical research literature, published abstracts, and clinical experience. The approach presented in this article is based on a combination of clinical experience and consultations with dermatologists, oncologists, and pharmacists familiar with EGFR inhibitor-associated rash.

Data Synthesis: A proactive approach that includes patient education and the use of a grade-based treatment algorithm. The goal of the approach is to minimize the effects of the rash on patients' quality of life and the course of cancer treatment.

Conclusions: Using the approach described in this article to treat the rash associated with the use of EGFR inhibitors, nurses can lessen patient discomfort and help ensure that patients will continue cancer treatment for as long as necessary.

Implications for Nursing: The approach described in this article should help nurses to recognize, grade, and treat the skin rash associated with EGFR inhibitors.

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    References

    Adjei, A.A. (2006). Novel combinations based on epidermal growth factor receptor inhibition. Clinical Cancer Research, 12(14, Pt. 2), 4446s-4450s.
    Agelaki, S., & Georgoulias, V. (2005). Epidermal growth factor receptor inhibitors in the treatment of non-small cell lung cancer. Expert Opinion on Emerging Drugs, 10(4), 855-874.
    Agero, A.L., Dusza, S.W., Benvenuto-Andrade, C., Busam, K.J., Myskowski, P., & Halpern, A.C. (2006). Dermatologic side effects associated with the epidermal growth factor receptor inhibitors. Journal of the American Academy of Dermatology, 55(4), 657-670.
    Albanell, J., Rojo, F., Averbuch, S., Feyereislova, A., Mascaro, J.M., Herbst, R., et al. (2002). Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: Histopathologic and molecular consequences of receptor inhibition. Journal of Clinical Oncology, 20(1), 110-124.
    Amgen. (2007). Vectibix (panitumumab) [Package insert]. Retrieved November 20, 2007, from http://www.amgen.com/pdfs/products/vectibix_pi.pdf
    ArcMesa Educators. (2006). The conundrum of rash in management of EGFR inhibitors. Retrieved November 20, 2007, from http://www.cmediscovery.com/EGFR
    AstraZeneca. (2005). Iressa® gefitinib tablets [Package insert]. Retrieved November 20, 2007, from http://www.astrazeneca-us.com/pi/iressa.pdf
    Baselga, J., & Arteaga, C.L. (2005). Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. Journal of Clinical Oncology, 23(11), 2445-2459.
    Berlin, J., Neubauer, M., Swanson, P., Harker, W.G., Burris, H., Hecht, J.R., et al. (2006). Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing > 10% epidermal growth factor receptor (EGFr) [Abstract 3548]. Journal of Clinical Oncology, 24(18s), 158s.
    Bonner, J.A., Harari, P.M., Giralt, J., Azarnia, N., Shin, D.M., Cohen, R.B., et al. (2006). Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. New England Journal of Medicine, 354(6), 567-578.
    Busam, K.J., Capodieci, P., Motzer, R., Kiehn, T., Phelan, D., & Halpern, A.C. (2001). Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. British Journal of Dermatology, 144(6), 1169-1176.
    Chan, S.K., Gullick, W.J., & Hill, M.E. (2006). Mutations of the epidermal growth factor receptor in non-small cell lung cancer—Search and destroy. European Journal of Cancer, 42(1), 17-23.
    Cunningham, D., Humblet, Y., Siena, S., Khayat, D., Bleiberg, H., Santoro, A., et al. (2004). Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. New England Journal of Medicine, 351(4), 337-345.
    Dancey, J.E., & Chen, H.X. (2006). Strategies for optimizing combinations of molecularly targeted anticancer agents. Nature Reviews: Drug Discovery, 5(8), 649-659.
    Del Rosso, J.Q. (2000). Systemic therapy for rosacea: Focus on oral antibiotic therapy and safety. Cutis, 66(4, Suppl.), 7-13.
    Dick, S.E., & Crawford, G.H. (2005). Managing cutaneous side effects of epidermal growth factor receptor (HER1/EGFR) inhibitors. Community Oncology, 2(6), 492-496.
    Eastern Cooperative Oncology Group. (n.d.). ECOG common toxicity criteria. Retrieved November 20, 2007, from http://www.ecog.org/general/ctc.pdf
    Foon, K.A., Yang, X.D., Weiner, L.M., Belldegrun, A.S., Figlin, R.A., Crawford, J., et al. (2004). Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. International Journal of Radiation Oncology, Biology, Physics, 58(3), 984-990.
    Frohna, P., Lu, J., Eppler, S., Hamilton, M., Wolf, J., Rakhit, A., et al. (2006). Evaluation of the absolute oral bioavailability and bioequivalence of erlotinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in a randomized, crossover study in healthy subjects. Journal of Clinical Pharmacology, 46(3), 282-290.
    Genentech. (2007). Tarceva® (erlotinib) [Package insert]. Retrieved November 20, 2007, from http://www.gene.com/gene/products/information/oncology/tarceva/insert.jsp
    Gross, M.E., Shazer, R.L., & Agus, D.B. (2004). Targeting the HER-kinase axis in cancer. Seminars in Oncology, 31(1, Suppl. 3), 9-20.
    Grunwald, V., & Hidalgo, M. (2003). Developing inhibitors of the epidermal growth factor receptor for cancer treatment. Journal of the National Cancer Institute, 95(12), 851-867.
    Herbst, R.S., & Bunn, P.A., Jr. (2003). Targeting the epidermal growth factor receptor in non-small cell lung cancer. Clinical Cancer Research, 9(16, Pt. 1), 5813-5824.
    Herbst, R.S., Prager, D., Hermann, R., Fehrenbacher, L., Johnson, B.E., Sandler, A., et al. (2005). TRIBUTE: A phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. Journal of Clinical Oncology, 23(25), 5892-5899.
    Hidalgo, M., & Bloedow, D. (2003). Pharmacokinetics and pharmacodynamics: Maximizing the clinical potential of erlotinib (Tarceva). Seminars in Oncology, 30(3, Suppl. 7), 25-33.
    Hidalgo, M., Siu, L.L., Nemunaitis, J., Rizzo, J., Hammond, L.A., Takimoto, C., et al. (2001). Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. Journal of Clinical Oncology, 19(13), 3267-3279.
    Hirsch, F.R., Varella-Garcia, M., Bunn, P.A., Jr., Di Maria, M.V., Veve, R., Bremmes, R.M., et al. (2003). Epidermal growth factor receptor in non-small-cell lung carcinomas: Correlation between gene copy number and protein expression and impact on prognosis. Journal of Clinical Oncology, 21(20), 3798-3807.
    Hynes, N.E., & Lane, H.A. (2005). ERBB receptors and cancer: The complexity of targeted inhibitors. Nature Reviews: Cancer, 5(5), 341-354.
    ImClone. (2006). Erbitux® (cetuximab) [Package insert]. Retrieved November 20, 2007, from http://packageinserts.bms.com/pi/pi_erbitux.pdf
    Indiana University Department of Medicine. (2007). Cytochrome p450 drug-interaction table. Retrieved December 11, 2007, from http://medicine.iupui.edu/flockhart/table.htm
    Jacot, W., Bessis, D., Jorda, E., Ychou, M., Fabbro, M., Pujol, J.L., et al. (2004). Acneform eruption induced by epidermal growth factor receptor inhibitors in patients with solid tumours. British Journal of Dermatology, 151(1), 238-241.
    Johnson, J.R., Cohen, M., Sridhara, R., Chen, Y.F., Williams, G.M., Duan, J., et al. (2005). Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clinical Cancer Research, 11(18), 6414-6421.
    Jost, M., Kari, C., & Rodeck, U. (2000). The EGF receptor—An essential regulator of multiple epidermal functions. European Journal of Dermatology, 10(7), 505-510.
    Kalyankrishna, S., & Grandis, J.R. (2006). Epidermal growth factor receptor biology in head and neck cancer. Journal of Clinical Oncology, 24(17), 2666-2672.
    Laux, I., Jain, A., Singh, S., & Agus, D.B. (2006). Epidermal growth factor receptor dimerization status determines skin toxicity to HER-kinase targeted therapies. British Journal of Cancer, 94(1), 85-92.
    Malik, I., Hecht, J.R., Patnaik, A., Venook, A., Berlin, J., Croghan, G., et al. (2005). Safety and efficacy of panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC) [Abstract 3520]. Journal of Clinical Oncology, 23(16s, Pt. 1), 251s.
    Meert, A.P., Martin, B., Delmotte, P., Berghmans, T., Lafitte, J.J., Mascaux, C., et al. (2002). The role of EGF-R expression on patient survival in lung cancer: A systematic review with meta-analysis. European Respiratory Journal, 20(4), 975-981.
    Mendelsohn, J., & Baselga, J. (2006). Epidermal growth factor receptor targeting in cancer. Seminars in Oncology, 33(4), 369-385.
    Moore, M.J., Goldstein, D., Hamm, J., Figer, A., Hecht, J., Gallinger, S., et al. (2007). Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. Journal of Clinical Oncology, 25(15), 1960-1966.
    National Cancer Institute. (2003). Definitions for CTCAE version 3.0. Bethesda, MD: Author.
    Nicholson, R.I., Gee, J.M., & Harper, M.E. (2001). EGFR and cancer prognosis. European Journal of Cancer, 37(Suppl. 4), S9-S15.
    Paine, M.F., Criss, A.B., & Watkins, P.B. (2004). Two major grapefruit juice components differ in intestinal CYP3A4 inhibition kinetic and binding properties. Drug Metabolism and Disposition, 32(10), 1146-1153.
    Peeters, M., Van Cutsem, E., Siena, S., Humblet, Y., Hendlisz, A., Neyns, B., et al. (2006, November). A phase 3, multicenter, randomized controlled trial (RCT) of panitumumab plus best supportive care (BSC) vs BSC alone in patients (pts) with metastatic colorectal cancer (mCRC). Presentation at the 18th EORTC-NCI-AACR Symposium on Molecular argets and Cancer Therapeutics, Prague, Czech Republic.
    Perez-Soler, R. (2003). Can rash associated with HER1/EGFR inhibition be used as a marker of treatment outcome? Oncology, 17(11, Suppl. 12), 23-28.
    Perez-Soler, R., Delord, J.P., Halpern, A., Kelly, K., Krueger, J., Sureda, B.M., 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), 345-356.
    Perez-Soler, R., & Saltz, L. (2005). Cutaneous adverse effects with HER1/EGFR-targeted agents: Is there a silver lining? Journal of Clinical Oncology, 23(22), 5235-5246.
    Perez-Soler, R., Zou, Y., Li, T., Tornos, C., & Ling, Y. (2006). Topical vitamin K3 (Vit K3, Menadione) prevents erlotinib and cetuximab-induced EGFR inhibition in the skin [Abstract 3036]. Journal of Clinical Oncology, 24(18s), 129s.
    Ravaud, A., Gardner, J., Hawkins, R., Von der Maase, H., Zantl, N., Harper, P., et al. (2006). Efficacy of lapatinib in patients with high tumor EGFR expression: Results of a phase III trial in advanced renal cell carcinoma (RCC) [Abstract 4502]. Journal of Clinical Oncology, 24(18s), 217s.
    Rhee, J., Oishi, K., Garey, J., & Kim, E. (2005). Management of rash and other toxicities in patients treated with epidermal growth factor receptor-targeted agents. Clinical Colorectal Cancer, 5(Suppl. 2), S101-S106.
    Robert, C., Soria, J.C., Spatz, A., Le Cesne, A., Malka, D., Pautier, P., et al. (2005). Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncology, 6(7), 491-500.
    Roe, E., Garcia Muret, M.P., Marcuello, E., Capdevila, J., Pallares, C., & Alomar, A. (2006). Description and management of cutaneous side effects during cetuximab or erlotinib treatments: A prospective study of 30 patients. Journal of the American Academy of Dermatology, 55(3), 429-437.
    Rowinsky, E.K. (2004). The erbB family: Targets for therapeutic development against cancer and therapeutic strategies using monoclonal antibodies and tyrosine kinase inhibitors. Annual Review of Medicine, 55, 433-457.
    Saif, M.W., & Cohenuram, M. (2006). Role of panitumumab in the management of metastatic colorectal cancer. Clinical Colorectal Cancer, 6(2), 118-124.
    Saltz, L.B., Meropol, N.J., Loehrer, P.J., Sr., Needle, M.N., Kopit, J., & Mayer, R.J. (2004). Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. Journal of Clinical Oncology, 22(7), 1201-1208.
    Sapadin, A.N., & Fleischmajer, R. (2006). Tetracyclines: Nonantibiotic properties and their clinical implications. Journal of the American Academy of Dermatology, 54(2), 258-265.
    Segaert, S., Tabernero, J., Chosidow, O., Dirschka, T., Elsner, J., Mancini, L., et al. (2005). The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies. Journal of the German Society of Dermatology, 3(8), 599-606.
    Segaert, S., & Van Cutsem, E. (2005). Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Annals of Oncology, 16(9), 1425-1433.
    Shah, N.T., Kris, M.G., Pao, W., Tyson, L.B., Pizzo, B.M., Heinemann, M.H., et al. (2005). Practical management of patients with non-small-cell lung cancer treated with gefitinib. Journal of Clinical Oncology, 23(1), 165-174.
    Shepherd, F.A., Rodrigues Pereira, J., Ciuleanu, T., Tan, E.H., Hirsh, V., Thongprasert, S., et al. (2005). Erlotinib in previously treated non-small-cell lung cancer. New England Journal of Medicine, 353(2), 123-132.
    Siegel-Lakhai, W.S., Beijnen, J.H., & Schellens, J.H. (2005). Current knowledge and future directions of the selective epidermal growth factor receptor inhibitors erlotinib (Tarceva) and gefitinib (Iressa). Oncologist, 10(8), 579-589.
    Silvestri, G.A., & Rivera, M.P. (2005). Targeted therapy for the treatment of advanced non-small cell lung cancer: A review of the epidermal growth factor receptor antagonists. Chest, 128(6), 3975-3984.
    Singh, B.N., & Malhotra, B.K. (2004). Effects of food on the clinical pharmacokinetics of anticancer agents: Underlying mechanisms and implications for oral chemotherapy. Clinical Pharmacokinetics, 43(15), 1127-1156.
    Smith, J. (2005). Erlotinib: Small-molecule targeted therapy in the treatment of non-small-cell lung cancer. Clinical Therapeutics, 27(10), 1513-1534.
    Strother, R.M., Jones, D.R., Skaar, T., Huh, W.S., Porter, J., Foster, A., et al. (2006). Erlotinib-associated rash correlates with plasma levels at steady state [Abstract 13008]. Journal of Clinical Oncology, 24(18s), 602s.
    Thatcher, N., Chang, A., Parikh, P., Rodrigues Pereira, J., Ciuleanu, T., von Pawel, J., et al. (2005). Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small cell lung cancer: Results from a randomized, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet, 366(9496), 1527-1537.
    Van Doorn, R., Kirtschig, G., Scheffer, E., Stoof, T.J., & Giaccone, G. (2002). Follicular and epidermal alterations in patients treated with ZD1839 (Iressa), an inhibitor of the epidermal growth factor receptor. British Journal of Dermatology, 147(3), 598-601.
    Yarden, Y. (2001). The EGFR family and its ligands in human cancer. Signalling mechanisms and therapeutic opportunities. European Journal of Cancer, 37(Suppl. 4), S3-S8.
    Yarden, Y., & Sliwkowski, M.X. (2001). Untangling the ErbB signalling network. Nature Reviews: Molecular Cell Biology, 2(27), 127-137.
    Zhou, B.B., Peyton, M., He, B., Liu, C., Girard, L., Caudler, E., et al. (2006). Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer. Cancer Cell, 10(1), 39-50.
    Herbst, R.S., Giaccone, G., Schiller, J.H., Natale, R.B., Miller, V., Manegold, C., et al. (2004). Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: A phase III trial—INTACT 2. Journal of Clinical Oncology, 22(5), 785-794.
    Herbst, R.S., LoRusso, P.M., Purdom, M., & Ward, D. (2003). Dermatologic side effects associated with gefitinib therapy: Clinical experience and management. Clinical Lung Cancer, 4(6), 366-369.