Retrospective Analysis of Skin Toxicity in Patients under Anti-EGFR Tyrosine Kinase Inhibitors: Our Experience in Lung Cancer
DOI:
https://doi.org/10.3889/oamjms.2019.170Keywords:
lung cancer, anti-EGFR, skin toxicity, rash, granulomaAbstract
BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been introduced for the treatment of lung cancer, improving progression-free survival, objective response rate, and quality of life. However, TKIs can lead to cutaneous toxicities, including papulopustular rash, xerosis, paronychia with/without pyogenic granulomas, scalp disorders, facial hair and/or eyelash growth.
AIM: In this study, we describe retrospectively all cases of mucocutaneous side effects in patients with lung cancer under TKIs referring to our outpatient for the skin care of oncological patients.
METHODS: We included patients referring from January 2016 to January 2018 affected by lung cancer and under TKIs. We collected data about the clinical exam, clinical photography, dermoscopy, histology and direct microscopic examination for each patient and we performed retrospectively descriptive analyses to assess whether a specific TKIs is linked significantly to particular cutaneous toxicity.
RESULTS: The majority of skin toxicities were due to afatinib, and the most common skin reaction was rash. We selected 60 patients with skin reactions, treated by TKIs for lung cancer. The majority of skin toxicities were due to afatinib (47/102 adverse reactions) and erlotinib (39/102). The most common skin reaction was rash (63% of patients), followed by xerosis (30%) and granulomas (30%). There was no significant relationship between a specific type of cutaneous reaction and specific EGFRi except for granulomas, developed more frequently in patients under afatinib (p < 0.05).
CONCLUSION: Most of our patients (63%) developed a cutaneous rash under TKIs. Most commonly afatinib was the drug involved, although it wasn’t the most used EGFRi. Moreover, we noticed a significant correlation between afatinib therapy and appearance of granulomas.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Data by World Health Organization http://www.who.int/entity/mediacentre/fact-sheets/fs297/en/
Zhang H. Three generations of epidermal growth factor receptor tyrosine kinase inhibitors developed to revolutionise the therapy of lung cancer. Drug Des Devel Ther. 2016; 10:3867-3872. https://doi.org/10.2147/DDDT.S119162 PMid:27920501 PMCid:PMC5125803
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361(10):947-57. https://doi.org/10.1056/NEJMoa0810699 PMid:19692680
Pastore S, Lulli D, Girolomoni G. Epidermal growth factor receptor signalling in keratinocyte biology: implications for skin toxicityof tyrosine kinase inhibitors. Arch Toxicol. 2014; 88(6):1189-203. https://doi.org/10.1007/s00204-014-1244-4 PMid:24770552
Califano R, Tariq N, Compton S, Fitzgerald DA, Harwood CA, Lal R, et al. Expert Consensus on the Management of Adverse Events from EGFR Tyrosine Kinase Inhibitorsin the UK. Drugs. 2015; 75(12):1335-48. https://doi.org/10.1007/s40265-015-0434-6 PMid:26187773 PMCid:PMC4532717
Hirsh V. Managing treatment-related adverse events associated with egfr tyrosine kinase inhibitors in advanced non-small-cell lung cancer. Curr Oncol. 2011; 18(3):126-38. https://doi.org/10.3747/co.v18i3.877 PMid:21655159 PMCid:PMC3108866
Nanba D, Toki F, Barrandon Y, Higashiyama S. Recent advances in the epidermal growth factor receptor/ligand system biology on skin homeostasis and keratinocyte stem cell regulation.J Dermatol Sci. 2013; 72(2):81-6. https://doi.org/10.1016/j.jdermsci.2013.05.009 PMid:23819985
Aw DC, Tan EH, Chin TM, Lim HL, Lee HY, Soo RA. Management of epidermal growth factor receptor tyrosine kinase inhibitor-related cutaneous and gastrointestinal toxicities. Asia Pac J Clin Oncol. 2018; 14(1):23-31. https://doi.org/10.1111/ajco.12687 PMid:28464435
Robert C, Soria JC, Spatz A, Le Cesne A, Malka D, Pautier P, et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol. 2005; 6(7):491-500. https://doi.org/10.1016/S1470-2045(05)70243-6
Arriola E, Reguart N, Artal A, Cobo M, GarcÃa-Campelo R, Esteban E, et al. Management of the adverse events of afatinib: a consensus of the recommendations of the Spanish expert panel. Future Oncol. 2015; 11(2):267-77. https://doi.org/10.2217/fon.14.214 PMid:25236437
Schiefer M, Hendriks LEL, Dinh T, Lalji U, Dingemans AC. Current perspective: Osimertinib-induced QT prolongation: new drugs with new side-effects needcareful patient monitoring. Eur J Cancer. 2018;91:92-98. https://doi.org/10.1016/j.ejca.2017.12.011 PMid:29413968
Chu CY, Chen KY, Wen-Cheng Chang J, Wei YF, Lee CH, Wang WM. Taiwanese Dermatological Association consensus for the prevention and management of epidermal growth factor receptor tyrosine kinase inhibitor-related skin toxicities. J Formos Med Assoc. 2017; 116(6):413-423. https://doi.org/10.1016/j.jfma.2017.03.001 PMid:28351555
Fischer A, Rosen AC, Ensslin CJ, Wu S, Lacouture ME. Pruritus to anticancer agents targeting the EGFR, BRAF, and CTLA-4. Dermatol Ther. 2013; 26(2):135-48. https://doi.org/10.1111/dth.12027 PMid:23551370
Pugliese SB, Neal JW, Kwong BY. Management of Dermatologic Complications of Lung Cancer Therapies. Curr Treat Options Oncol. 2015; 16(10):50. https://doi.org/10.1007/s11864-015-0368-y PMid:26338208
Overbeck TR, Griesinger F. Two cases of psoriasis responding to erlotinib: time to revisiting inhibition of epidermal growthfactor receptor in psoriasis therapy? Dermatology. 2012; 225(2):179-82. https://doi.org/10.1159/000342786 PMid:23095682
Zorzou MP, Stratigos A, Efstathiou E, Bamias A. Exacerbation of psoriasis after treatment with an EGFR tyrosine kinase inhibitor. Acta Derm Venereol. 2004; 84(4):308-9. https://doi.org/10.1080/00015550410024634 PMid:15339078
Melosky B, Hirsh V. Management of Common Toxicities in Metastatic NSCLC Related to Anti-Lung Cancer Therapieswith EGFR-TKIs. Front Oncol. 2014; 4:238. https://doi.org/10.3389/fonc.2014.00238 PMid:25279350 PMCid:PMC4165207
Dueland S, Sauer T, Lund-Johansen F, Ostenstad B, Tveit KM. Epidermal growth factor receptor inhibition induces trichomegaly. Acta Oncol. 2003; 42(4):345-6. https://doi.org/10.1080/02841860310006038 PMid:12899508
Razis E, Karina M, Karanastassi S, Fountzilas G. Three case reports of hand-foot syndrome with gefitinib. Cancer Invest. 2006; 24(5):514-6. https://doi.org/10.1080/07357900600814847 PMid:16939960
Zheng Y, Fang W, Xu N. Hand-foot syndrome in a patient with metastatic lung adenocarcinoma induced by high-dose icotinib: A case report and review of the literature. Oncol Lett. 2012; 4(6):1341-1343. https://doi.org/10.3892/ol.2012.904 PMid:23205134 PMCid:PMC3506748
Dai J, Belum VR, Wu S, Sibaud V, Lacouture ME. Pigmentary changes in patients treated with targeted anticancer agents: A systematic review and meta-analysis. J Am Acad Dermatol. 2017; 77(5):902-910. https://doi.org/10.1016/j.jaad.2017.06.044 PMid:28918974 PMCid:PMC5657394
Kozuki T. Skin problems and EGFR-tyrosine kinase inhibitor. Jpn J Clin Oncol. 2016; 46(4):291-8. https://doi.org/10.1093/jjco/hyv207 PMid:26826719 PMCid:PMC4886131
Holcmann M, Sibilia M. Mechanisms underlying skin disorders induced by EGFR inhibitors. Mol Cell Oncol. 2015; 2(4):e1004969. https://doi.org/10.1080/23723556.2015.1004969 PMid:27308503 PMCid:PMC4905346
Peréz-Soler R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol. 2005; 23(22):5235-46. https://doi.org/10.1200/JCO.2005.00.6916 PMid:16051966
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2019 Maria Carmela Annunziata, Maria Ferrillo, Eleonora Cinelli, Luigia Panariello, Danilo Rocco, Gabriella Fabbrocini
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0
