Dermatologic adverse events associated with epidermal growth factor receptor inhibitors: current concepts of interdisciplinary problem
https://doi.org/10.17650/2222-1468-2021-11-4-97-109
Abstract
Epidermal growth factor receptor inhibitors (EGFR) have a high rate of class-specific dermatologic adverse events. Supportive treatment of dermatologic adverse events decreases their severity, minimizes the need for dose de-escalation / discontinuation of targeted therapy, improves commitment to anticancer treatment and patient’s quality of life. Close interdisciplinary cooperation between oncologists and dermatologists is a key to the successful management of patients treated with EGFR. This article highlights current approaches to classification, concepts of pathogenesis and clinical course of EGFR-associated dermatologic adverse events, current and promising prophylactic and therapeutic strategies to manage these adverse events.
About the Authors
A. S. Polonskaia
Central State Medical Academy of the Presidential Administration of the Russian Federation; Medical Scientific and Educational Center of M. V. Lomonosov Moscow State University
Russian Federation
Russian Federation
Bld. 1a, 19 Marshala Timoshenko St., Moscow 121359
Bld. 10, 27 Lomonosovsky Prospekt, Moscow 119192
E. A. Shatokhina
Central State Medical Academy of the Presidential Administration of the Russian Federation; Medical Scientific and Educational Center of M. V. Lomonosov Moscow State University
Russian Federation
Russian Federation
Bld. 1a, 19 Marshala Timoshenko St., Moscow 121359
Bld. 10, 27 Lomonosovsky Prospekt, Moscow 119192
L. S. Kruglova
Central State Medical Academy of the Presidential Administration of the Russian Federation
Russian Federation
Russian Federation
Bld. 1a, 19 Marshala Timoshenko St., Moscow 121359
References
1. International Agency for Research on Cancer. Cancer tuday. Estimated number of new cases in 2020, worldwide, both sexes, all ages. Avaliable at: https://gco.iarc.fr/today/online-analysispie?v=2020&mode=cancer&mode_population=continents&population=900&populations=900&key=total&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&nb_items=7&group_cancer=1&include_nmsc=1&include_nmsc_other=1&half_pie=0&donut=0.
2. International Agency for Research on Cancer – Estimated number of deaths in 2020, worldwide, both sexes, all ages. Avaliable at: https://gco.iarc.fr/today/online-analysis-pie?v=2020&mode=cancer&mode_population=continents&population=900&populations=900&key=total&sex=0&cancer=39&type=1&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&nb_items=7&group_cancer=1&include_nmsc=1&include_nmsc_other=1&half_pie=0&donut=0.
3. Seebacher N.A., Stacy A.E., Porter G.M. et al. Clinical development of targeted and immune based anti-cancer therapies. J Exp Clin Cancer Res 2019;38(1):156. DOI: 10.1186/s13046-019-1094-2.
4. Lacouture M.E., Anadkat M.J., Bensadoun R.J. et al. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer 2011;19(8):1079–95.
5. Lacouture M.E., Sibaud V., Gerber P.A. et al. Prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines. Ann Oncol 2021;32(2):157–70. DOI: 10.1016/j.annonc.2020.11.005.
6. Peuvrel L., Bachmeyer C., Reguiai Z. et al. Semiology of skin toxicity associated with epidermal growth factor receptor (EGFR) inhibitors. Support Care Cancer 2012;20(5):909–21. DOI: 10.1007/s00520-012-1404-0.
7. Boone S.L., Rademaker A., Liu D. et al. Impact and management of skin toxicity associated with anti-epidermal growth factor receptor therapy: survey results. Oncology 2007;72(3–4):152–9. DOI: 10.1159/000112795.
8. Rosen A.C., Case E.C., Dusza S.W. et al. Impact of dermatologic adverse events on quality of life in 283 cancer patients: a questionnaire study in a dermatology referral clinic. Am J Clin Dermatol 2013;14(4):327–33. DOI: 10.1007/s40257-013-0021-0.
9. Shatokhina E.A., Kruglova L.S., Polonskaia A.S. Management of acneiform rash associated with anti-EGFR monoclonal antibody treatment. Meditsinskiy sovet = Medical Council 2020;(20):157–64. (In Russ.). DOI: 10.21518/2079-701X2020-20-157-164.
10. Petrelli F., Borgonovo K., Cabiddu M. et al. Relationship between skin rash and outcome in non-small-cell lung cancer patients treated with anti-EGFR tyrosine kinase inhibitors: a literaturebased meta-analysis of 24 trials. Lung Cancer 2012;78(1):8–15. DOI: 10.1016/j.lungcan.2012.06.009.
11. Liu H.B., Wu Y., Lv T.F. et al. Skin rash could predict the response to EGFR tyrosine kinase inhibitor and the prognosis for patients with non-small cell lung cancer: a systematic review and metaanalysis. PLoS One 2013;8(1):e55128. DOI: 10.1371/journal.pone.0055128.
12. Lacouture M.E. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 2006;6(10):803–12. DOI: 10.1038/nrc1970.
13. Nanney L.B., Stoscheck C.M., King L.E. et al. Immunolocalization of epidermal growth factor receptors in normal developing human skin. J Invest Dermatol 1990;94(6):742–8. DOI: 10.1111/1523-1747.ep12874601.
14. Nanney L.B., Magid M., Stoscheck C.M., King L.E. Comparison of epidermal growth factor binding and receptor distribution in normal human epidermis and epidermal appendages. J Invest Dermatol 1984;83(5):385–93. DOI: 10.1111/1523-1747.ep12264708.
15. Han S.S., Lee M., Park G.H. et al. Investigation of papulopustular eruptions caused by cetuximab treatment shows altered differentiation markers and increases in inflammatory cytokines. Br J Dermatol 2010;162(2):371–9. DOI: 10.1111/j.1365-2133.2009.09536.x.
16. Lichtenberger B.M., Gerber P.A., Holcmann M. et al. Epidermal EGFR controls cutaneous host defense and prevents inflammation. Sci Transl Med 2013;5(199):199ra111. DOI: 10.1126/scitranslmed.3005886.
17. Busam K.J., Capodieci P., Motzer R. et al. Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Br J Dermatol 2001;144(6):1169–76. DOI: 10.1046/j.1365-2133.2001.04226.x.
18. Galimont-Collen A.F., Vos L.E., Lavrijsen A.P. et al. Classification and management of skin, hair, nail and mucosal side-effects of epidermal growth factor receptor (EGFR) inhibitors. Eur J Cancer 2007;43(5):845–51. DOI: 10.1016/j.ejca.2006.11.016.
19. Nardone B., Nicholson K., Newman M. et al. Histopathologic and immunohistochemical characterization of rash to human epidermal growth factor receptor 1 (HER1) and HER1/2 inhibitors in cancer patients. Clin Cancer Res 2010;16(17):4452–60. DOI: 10.1158/1078-0432.CCR-10-0421.
20. Ho P.H., Lin I.C., Yang X. et al. Using a novel scoring system for paronychia related to oncologic treatments (SPOT) for assessing paronychia severity and its correlation with pain index and quality of life. J Eur Acad Dermatol Venereol 2019;33:204–12. DOI: 10.1111/jdv.15121.
21. Gerber P.A., Kukova G., Buhren B.A., Homey B. Density of Demodex folliculorum in patients receiving epidermal growth factor receptor inhibitors. Dermatology 2011;222(2):144–7. DOI: 10.1159/000323001.
22. Miettinen P.J., Berger J.E., Meneses J. et al. Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 1995;376(6538):337–41. DOI: 10.1038/376337a0.
23. Segaert S., Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol 2005;16(9):1425–33. DOI: 10.1093/annonc/mdi279.
24. Gerber P.A., Buhren B.A., Cevikbas F. et al. Preliminary evidence for a role of mast cells in epidermal growth factor receptor inhibitor-induced pruritus. J Am Acad Dermatol 2010;63(1):163–5. DOI: 10.1016/j.jaad.2009.09.023.
25. Bragado R., Bello E., Requena L. et al. Increased expression of vascular endothelial growth factor in pyogenic granulomas. Acta Derm Venereol 1999;79:422–5. DOI: 10.1080/000155599750009834.
26. Perrotte P., Matsumoto T., Inoue K. et al. Anti-epidermal growth factor receptor antibody C225 inhibits angiogenesis in human transitional cell carcinoma growing orthotopically in nude mice. Clin Cancer Res 1999;5(2):257–65.
27. Murillas R., Larcher F., Conti C.J. et al. Expression of a dominant negative mutant of epidermal growth factor receptor in the epidermis of transgenic mice elicits striking alterations in hair follicle development and skin structure. EMBO J 1995;14(21):5216–23.
28. Threadgill D.W., Dlugosz A.A., Hansen L.A. et al. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science 1995;269(5221):230–4. DOI: 10.1126/science.7618084.
29. Koroleva I.A., Bolotina L.V., Gladkov O.A. et al. Practical recommendations on the management of dermatologic adverse events in patients, treated with targeted anticancer drugs. Zlokachestvennye opuholi. prakticheskie rekomendacii RUSSCO #3s2 = Malignant tumors: practical recommendations RUSSCO #3s2 2020;10(42):88–101. (In Russ.). Avaliable at: https://www.rosoncoweb.ru/standarts/RUSSCO/2020/2020-42.pdf.
30. Robert C., Soria J.C., Spatz A. et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol 2005;6(7):491–500. DOI: 10.1016/S1470-2045(05)70243-6.
31. Lynch T.J., Kim E.S., Eaby B. et al. Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist 2007;12(5):610-21. DOI:10.1634/theoncologist.12-5-610.
32. Shatokhina E.A., Kruglova L.S., Polonskaia A.S., Nosikova P.G. Acneiform rash – dermatologic adverse event in the therapy with anti-EGFR monoclonal antibodies. Farmateka = Pharmateca 2020;27(8):56–60. (In Russ.). DOI: 10.18565pharmateca.2020.8.56-60.
33. Bonner J.A., Ang K. More on severe cutaneous reaction with radiotherapy and cetuximab. N Engl J Med 2007;357(18):1872–3. DOI: 10.1056/NEJMc076359.
34. Bernier J., Bonner J., Vermorken J.B. et al. Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck. Ann Oncol 2008;19(1):142–9. DOI: 10.1093/annonc/mdm400.
35. Wheatley-Price P., Ding K., Seymour L. et al. Erlotinib for advanced non-smallcell lung cancer in the elderly: an analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008;26(14):2350–7. DOI: 10.1200/JCO.2007.15.2280.
36. Bigot F., Boudou-Rouquette P., Arrondeau J. et al. Erlotinib pharmacokinetics: a critical parameter influencing acute toxicity in elderly patients over 75 years-old. Invest New Drugs 2017;35(2):242–6. DOI: 10.1007/s10637-016-0400-5.
37. Jatoi A., Green E.M., Rowland K.M. et al. Clinical predictors of severe cetuximabinduced rash: observations from 933 patients enrolled in north central cancer treatment group study N0147. Oncology 2009;77(2):120–3. DOI: 10.1159/000229751.
38. Osio A., Mateus C., Soria J.C. et al. Cutaneous side-effects in patients on longterm treatment with epidermal growth factor receptor inhibitors. Br J Dermatol 2009;161(3):515–21. DOI: 10.1111/j.1365-2133.2009.09214.x.
39. Tsimboukis S., Merikas I., Karapanagiotou E.M. et al. Erlotinib-induced skin rash in patients with non-small-cell lung cancer: pathogenesis, clinical significance, and management. Clin Lung Cancer 2009;10(2): 106–11. DOI: 10.3816/CLC.2009.n.013.
40. Ensslin C.J., Rosen A.C., Wu S., Lacouture M.E. Pruritus in patients treated with targeted cancer therapies: systematic review and meta-analysis. J Am Acad Dermatol 2013;69(5):708–20. DOI: 10.1016/j.jaad.2013.06.038.
41. Hu J.C., Sadeghi P., Pinter-Brown L.C. et al. Cutaneous side effects of epidermal growth factor receptor inhibitors: clinical presentation, pathogenesis, and management. J Am Acad Dermatol 2007;56(2):317–26. DOI: 10.1016/j.jaad.2006.09.005.
42. Melichar B., Nemcová I. Eye complications of cetuximab therapy. Eur J Cancer Care (Engl) 2007;16(5):439–43. DOI: 10.1111/j.1365-2354.2006.00763.x.
43. Lacouture M.E., Lai S.E. The PRIDE (Papulopustules and/or paronychia, Regulatory abnormalities of hair growth, Itching, and Dryness due to Epidermal growth factor receptor inhibitors) syndrome. Br J Dermatol 2006;155(4): 852–4. DOI: 10.1111/j.1365-2133.2006.07452.x.
44. Pérez-Soler R., Delord J.P., Halpern A. et al. HER1/EGFR inhibitor-associated rash: future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum. Oncologist 2005;10(5):345–56. DOI: 10.1634/theoncologist.10-5-345.
45. Roé E., García Muret M.P., Marcuello E. et al. Description and management of cutaneous side effects during cetuximab or erlotinib treatments: a prospective study of 30 patients. J Am Acad Dermatol 2006;55(3):429–37. DOI: 10.1016/j.jaad.2006.04.062.
46. Porzio G., Aielli F., Verna L. et al. Efficacy of pregabalin in the management of cetuximab-related itch. J Pain Symptom Manage 2006;32(5):397–8. DOI: 10.1016/j.jpainsymman.2006.07.006.
47. Sollena P., Mannino M., Tassone F. et al. Efficacy of topical beta-blockers in the management of EGFR-inhibitor induced paronychia and pyogenic granuloma-like lesions: case series and review of the literature. Drugs Context 2019;8:212613. DOI: 10.7573/dic.212613.
48. Yen C.F., Hsu C.K., Yang H.S. et al. Treatment of epidermal growth factor receptor inhibitor-induced severe paronychia with pyogenic granuloma-like lesions with topical betaxolol: an openlabel observation study. Int J Dermatol 2020;59(3):326–32. DOI: 10.1111/ijd.14730.
49. Denda M., Fuziwara S., Inoue K. Beta2adrenergic receptor antagonist accelerates skin barrier recovery and reduces epidermal hyperplasia induced by barrier disruption. J Invest Dermatol 2003;121(1):142–8. DOI: 10.1046/j.1523-1747.2003.12310.x.
50. Sibaud V., Casassa E., D’Andrea M. Are topical beta-blockers really effective “in real life” for targeted therapy-induced paronychia. Support Care Cancer 2019;27(7):2341–3. DOI: 10.1007/s00520-019-04690-8.
51. Panariello L., Donnarumma M., Cinelli E., Fabbrocini G. Case series showing the efficacy of 5-aminolaevulinic acid photodynamic therapy for epidermal growth factor receptor inhibitor-induced paronychia and pyogenic granuloma-like lesions. Br J Dermatol 2019;180(3):676–7. DOI: 10.1111/bjd.17270.
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For citations:
Polonskaia A.S., Shatokhina E.A., Kruglova L.S. Dermatologic adverse events associated with epidermal growth factor receptor inhibitors: current concepts of interdisciplinary problem. Head and Neck Tumors (HNT). 2021;11(4):97-109. (In Russ.) https://doi.org/10.17650/2222-1468-2021-11-4-97-109
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