Managing dermatologic changes of targeted cancer therapy

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Applied Evidence

Managing dermatologic changes of targeted cancer therapy

J Fam Pract. 2019 July;68(6):334-340

By

Kevin Zarrabi, MD, MSc

Julie Anne L. Gemmill, DO

Maryam Safaee, MD

Lea Baer, MD

Failure to control these dermatologic changes can lead to lower dosages of cancer agents or an interrupted course of Tx. These steps can help you to head off trouble.

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PRACTICE RECOMMENDATIONS

› Counsel patients about their risk of rash before epidermal growth factor receptor–targeting treatment is initiated; early recognition of rash and intervention lead to milder symptoms. A

› Encourage daily skin care with an alcohol-free emollient cream. Instruct patients to avoid products that can cause skin drying, prolonged hot showers, perfumes, and soaps marketed for treating acne. B

› Instruct patients that oral hygiene to lower their risk of stomatitis should include a soft-bristle toothbrush and oral rinsing with normal saline—not with an alcohol-based commercial mouthwash. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

References

1. Phillips JL, Currow DC. Cancer as a chronic disease. Collegian. 2010;17:47-50.

2. Klabunde CN, Ambs A, Keating NL, et al. The role of primary care physicians in cancer care. J Gen Intern Med. 2009;24:1029-1036.

3. Agha R, Kinahan K, Bennett CL, et al. Dermatologic challenges in cancer patients and survivors. Oncology (Williston Park). 2007;21:1462-1472; discussion 1473,1476,1481 passim.

4. Mitchell EP, Pérez-Soler R, Van Cutsem, et al. Clinical presentation and pathophysiology of EGFRI dermatologic toxicities. Oncology (Williston Park). 2007;21(11 suppl 5):4-9.

5. Liu S, Kurzrock R. Understanding toxicities of targeted agents: implications for anti-tumor activity and management. Semin Oncol. 2015;42:863-875.

6. Romito F, Giuliani F, Cormio C, et al. Psychological effects of cetuximab-induced cutaneous rash in advanced colorectal cancer patients. Support Care Cancer. 2010;18:329-334.

7. Wacker B, Nagrani T, Weinberg J, et al. Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies. Clin Cancer Res. 2007;13:3913-3921.

8. Chou LS, Garey J, Oishi K, et al. Managing dermatologic toxicities of epidermal growth factor receptor inhibitors. Clin Lung Cancer. 2006;8(suppl 1):S15-S22.

9. Li T, Pérez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. Target Oncol. 2009;4:107-119.

10. Su X, Lacouture ME, Jia Y, et al. Risk of high-grade skin rash in cancer patients treated with cetuximab—an antibody against epidermal growth factor receptor: systemic review and meta- analysis. Oncology. 2009;77:124-133.

11. Luu M, Boone SL, Patel J, et al. Higher severity grade of erlotinib-induced rash is associated with lower skin phototype. Clin Exp Dermatol. 2011;36:733-738.

12. Jatoi A, Green EM, Rowland KM Jr, et al. Clinical predictors of severe cetuximab-induced rash: observations from 933 patients enrolled in North Central Cancer Treatment Group study N0147. Oncology. 2009;77:120-123.

13. Drugs@FDA: FDA approved drug products. US Food and Drug Administration Web site. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed June 4, 2019.

14. Melosky B, Burkes R, Rayson D, et al. Management of skin rash during EGFR-targeted monoclonal antibody treatment for gastrointestinal malignancies: Canadian recommendations. Curr Oncol. 2009;16:16-26.

15. Lacouture ME, Melosky BL. Cutaneous reactions to anticancer agents targeting the epidermal growth factor receptor: a dermatology-oncology perspective. Skin Therapy Lett. 2007; 12:1-5.

16. Eaby B, Culkin A, Lacouture ME. An interdisciplinary consensus on managing skin reactions associated with human epidermal growth factor receptor inhibitors. Clin J Oncol Nurs. 2008; 12:283-290.

17. Hirsh V. Managing treatment-related adverse events associated with EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer. Curr Oncol. 2011;18:126-138.

18. Reguiai Z, Bachet JB, Bachmeyer C, et al. Management of cuta- neous adverse events induced by anti-EGFR (epidermal growth factor receptor): a French interdisciplinary therapeutic algo- rithm. Support Care Cancer. 2012;20:1395-1404.

19. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. 2016;65:1-49.

20. Pérez-Soler R, Delord JP, 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;10:345-356.

21. Bidoli P, Cortinovis DL, Colombo I, et al. Isotretinoin plus clindamycin seem highly effective against severe erlotinib-induced skin rash in advanced non-small cell lung cancer. J Thorac Oncol. 2010;5:1662-1663.

22. Vezzoli P, Marzano AV, Onida F, et al. Cetuximab-induced ac - neiform eruption and the response to isotretinoin. Acta Derm Venereol. 2008;88:84-86.

23. Rittié L, Varani J, Kang S, et al. Retinoid-induced epidermal hyperplasia is mediated by epidermal growth factor receptor activation via specific induction of its ligands heparin-binding EGF and amphiregulin in human skin in vivo. J Invest Dermatol. 2006;126:732-739.

24. Jatoi A, Thrower A, Sloan JA, et al. Does sunscreen prevent epidermal growth factor receptor (EGFR) inhibitor-induced rash? Results of a placebo-controlled trial from the North Central Cancer Treatment Group (N05C4). Oncologist. 2010; 15:1016-1022.

25. Lynch TJ Jr, Kim ES, Eaby B, et al. Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist. 2007;12:610-621.

26. Harandi A, Zaidi AS, Stocker AM, et al. Clinical efficacy and toxicity of anti-EGFR therapy in common cancers. J Oncol. 2009;2009:567486.

27. Petrelli F, Borgonovo K, Cabiddu M, et al. Antibiotic prophylaxis for skin toxicity induced by antiepidermal growth factor receptor agents: a systematic review and meta-analysis. Br J Dermatol. 2016;175:1166-1174.

28. Scope A, Agero AL, Dusza SW, et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol. 2007;25:5390-5396.

29. Lacouture ME, Anadkat MJ, Bensadoun RJ, et al; MASCC Skin Toxicity Study Group. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011;19:1079-1095.

30. Melosky B, Leighl NB, Rothenstein J, et al. Management of egfr tki-induced dermatologic adverse events. Curr Oncol. 2015; 22:123-132.

31. Arrieta O, Vega-González MT, López-Macías D, et al. Randomized, open-label trial evaluating the preventive effect of tetracycline on afatinib induced-skin toxicities in non-small cell lung cancer patients. Lung Cancer. 2015;88:282-288.

32. Saito H, Watanabe Y, Sato K, et al. Effects of professional oral health care on reducing the risk of chemotherapy-induced oral mucositis. Support Care Cancer. 2014;22:2935-2940.

33. Kozuki T. Skin problems and EGFR-tyrosine kinase inhibitor. Jpn J Clin Oncol. 2016;46:291-298.

Advances in cancer therapy have improved survival, such that many cancers have been transformed from a terminal illness to a chronic disease, and the population of patients living with cancer or who are disease-free has grown. However, these patients face complex medical problems because of the systemic effects of their treatment and many endure a constellation of treatment-emergent adverse effects that require ongoing care and support.¹

Primary care physicians have been called on to take a larger role in the care of these adverse effects as the growing number of treatments has meant more affected patients. In addition, an urgent, unmet need has developed for better coordination between specialists and family physicians for providing this supportive care.²

In this article, we (1) describe the most commonly encountered cancer treatment–related skin toxicities, paying particular attention to the effects of epidermal growth factor receptor (EGFR)–targeting therapies, and (2) review up-to-date management recommendations in an area of practice where established clinical guidance from the scientific literature is limited.

Biggest culprit: Targeted cancer therapies

Skin rash and dermatologic adverse effects are commonplace in patients undergoing cancer treatment; timely management can often prevent long-term skin damage.³ Dermatologic effects have been associated with various therapeutic agents, but are most commonly associated with targeted therapies—specifically, agents targeting EGFR.

Why the attention to EGFR inhibition? EGFR is overexpressed or mutated in a multitude of solid tumors; as such, agents have been developed that target this aberrant signaling pathway. EGFR is highly expressed in the skin and dermal tissue, where it plays a number of roles, including protection against ultraviolet radiation damage.⁴

Overall, incidence of EGFR inhibitor–related rash ranges from 45% to 100% of treated patients.

Blockade of the EGFR molecule leads to dermal changes, however, presenting as acneiform rash, skin fissure and xerosis, and pruritus.⁵ In extreme instances, toxic effects can manifest as paronychia, facial hypertrichosis, and trichomegaly. These skin changes can be deforming as well as painful, and can have physiological and psychological consequences.⁶

In turn, a decrease in quality of life (as reported by patients suffering from skin toxicity) can affect cancer treatment adherence and efficacy,⁷ and severe skin changes can result in the need to reduce the dosage of anti-cancer therapies.⁸ Skillful evaluation and appropriate management of skin eruptions in patients undergoing cancer therapy is therefore vital to an overall satisfactory outcome.

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