The most common skin manifestation of epidermal growth factor receptor inhibitors is a papulopustular eruption that typically develops 8-10 days after the beginning of therapy, mainly on the scalp and in other areas with a high concentration of sebaceous glands, according to a review of the topic.
"Although the eruption typically spontaneously resolves after 12 weeks of EGFR inhibitor therapy, long-term postinflammatory erythema or hyperpigmentation is not unusual and may last for years after therapy has been discontinued," Rachel L. Kyllo and Dr. Milan J. Anadkat wrote in Seminars in Cutaneous Medicine and Surgery (in press).
As part of a larger review of the cutaneous manifestations of chemotherapeutic agents, Ms. Kyllo and Dr. Anadkat of the division of dermatology at Washington University, St. Louis, noted that EGFR receptor inhibitors have been approved for treating solid tumors including pancreatic cancer, non–small cell lung cancer, colorectal cancer, head and neck squamous cell cancer, and breast cancer. The two main types are small molecule inhibitors, including gefitinib, erlotinib,and lapatinib, and the monoclonal antibodies cetuximab and panitumumab.
Monoclonal antibodies are associated with a higher incidence of papulopustular eruption. Histology "demonstrates a mixed superficial inflammatory infiltrate which leads to follicular rupture and acantholysis," the authors wrote. "These findings are consistent with dysregulation of molecular pathways downstream from EGFR signaling, which are known to be important in keratinocyte migration, maturation, and survival."
Although having an EGFR inhibitor–related papulopustular eruption appears to be associated with an increased median survival time, high-grade rash often leads to treatment modification or dose adjustment. "Prophylactic treatment with systemic tetracycline antibiotics for the first 8 weeks of EGFR inhibitor therapy significantly reduces the severity of the papulopustular eruption, theoretically decreasing the need for dosage adjustment," the authors wrote. "Severe cases should prompt consideration of systemic therapy with corticosteroids, low-dose isotretinoin, or acitretin."
EGFR inhibitor therapy also can affect the hair, most commonly causing a change in hair texture with increased breakability and curliness. This side effect is more likely with long-term exposure and can appear months after treatment begins. "Nonscarring alopecia typically develops 8-12 weeks after initiation of EGFR inhibitor therapy in 5% of patients and resolves spontaneously after discontinuation of the drug," the authors added. "Rarely, scarring alopecia results in permanent hair loss; prophylactic doxycycline to reduce papulopustular eruption severity ... and topical high-dose corticosteroid preparations reduce the likelihood of subsequent scarring."
They went on to note that 12%-16% of patients develop paronychia 8-12 weeks after initiation of EGFR therapy, with local trauma believed to be an aggravating factor. A course of antibiotics is warranted only in cases of culture-proven bacterial superinfection.
Another potential side effect of EGFR therapy, xerosis, occurs in 4%-35% of patients, usually 4-8 weeks after initiation of treatment. It most commonly affects elderly patients, as well as those with preexisting eczema and those who have undergone prior treatment with cytotoxic agents. "Treatments include topical emollients and keratolytics; use of topical retinoids or benzoyl peroxide is not recommended as they may exacerbate skin dryness," the authors wrote. "Use of topical corticosteroids is reserved for cases of frank dermatitis."
Dr. Anadkat disclosed having received honoraria as a consultant and/or speaker from ImClone, Genentech, AstraZeneca, Therakos, Eisai, and Bristol-Myers Squibb.