Treatment of epidermal growth factor receptor inhi

Authors: Jonathan Cotliar

Publish Date: 2011/08/04

Volume: 19, Issue: 10, Pages: 1481-

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Abstract

The recognition and treatment of cutaneous toxicities as a consequence of epidermal growth factor receptor inhibitor EGFRi use in the treatment of several solid tumors has led to the increasing involvement of dermatologists in the care of cancer patients Unlike traditional chemotherapeutic agents where cutaneous complications are more rare EGFRis frequently induce a variety of skin effects that are both predictable and often severe enough to warrant delaying of treatment or even permanent discontinuation 1 As a result it is in the interest of all parties patients physicians drug manufacturers to devise strategies that will minimize these adverse events to allow for maintenance of cancer therapy Despite the convergence of such interests there has been a lack of data based on welldesigned randomized and controlled studies from which practitioners can reasonably draw in order to treat these patients when side effects do develop Though Lacouture et al have provided a comprehensive and exhaustive review of EGFRirelated toxicities there continues to be a dearth of validated data concerning management of these treatment complications and a lack of consensus as to how best to approach the majority of patients on EGFRis that will ultimately develop skin toxicitiesIn their review Lacouture et al allude to the fact that the bulk of interventions used to treat the papulopustular eruption associated with EGFRis are based mostly on case reports or small case series Of the randomized trials that have been performed there is conflicting evidence in support of what still remains the standard approach to treatment of this specific reaction typically a combination of a tetracyclinebased oral antibiotic prescribed either prophylactically immediately before EGFRi initiation or shortly thereafter once skin lesions have developed but have not yet reached peak severity Low to mediumpotency topical corticosteroids are also commonly used to combat papulopustular lesions when they develop Jatoi et al previously concluded that while prophylactic tetracycline does not diminish rash incidence it seems to ameliorate the severity of papulopustular rash as compared to placebo in addition to improving quality of life of patients on EGFRis 2 Adding support to the notion of the efficacy of prophylactic tetracycline was the skin toxicity evaluation protocol with panitumumab trial which demonstrated that prophylactic oral doxycycline emollients topical corticosteroids and sunscreen were able to provide a greater than 50 reduction in the incidence of grade II or greater cutaneous toxicities 3 These results followed what had been documented 2 years prior with prophylactic oral minocycline allowing for a reduction in the severity of papulopustular eruptions seen in patients on cetuximab during the first month of cancer therapy 4Grading of cutaneous toxicities has been problematic even as the schema have adapted to account for skin eruptions unique to EGFRis and other targeted cancer agents Jatoi et al recently concluded that prophylactic tetracycline does not reduce either the incidence or severity of skin eruptions for patients on EGFRis 5 However this randomized doubleblinded and placebocontrolled study employed CTCAE version 30 which is fraught with deficiencies when grading EGFRiinduced papulopustular eruptions In this version grade I eruptions are differentiated from grade II only on the basis of the presence of symptoms such as pain or pruritus Furthermore grade III is differentiated from grade II on the basis of either less than 50 body surface area of involvement grade II or greater than 50 involvement grade III No nuance within that version allows for the common presentation of patients on EGFRis with either asymptomatic but diffuse 50 involvement eruptions or those patients with papules and pustules on only a limited amount of skin but with severe pain or pruritus CTCAE version 40 improves upon these shortcomings by using more incremental measurements of percentage of body surface area affected in grades I–III and includes previously ignored features such as interference with ADLs and presence of superinfection It would be interesting to see if the employment of CTCAE 40 and restratification of subjects based on the newer version would be able to detect differences in the number of patients with grades II and III skin eruptions by these new criteria and whether such differences would have any impact on the conclusion of Jatois studyIn the short term it is likely that dermatologists will continue to use oral tetracyclines and topical steroids for patients on EGFRis unless contraindicated because of the lack of an established alternative even with murky data to support their use It is imperative that oncologists and dermatologists work together to enroll patients in welldesigned trials that use sensible and uniform grading of skin sequelae in order to produce consensus for patients that ideally can maintain their course of cancer treatment with little or no interruption

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