Analysis of risk factors for skin disorders caused by anti‐epidermal growth factor receptor antibody drugs and examination of methods for their avoidance

Abstract

What is known and Objective: Cancer drug treatment is often discontinued because of skin disorder aggravation. However, information on risk factors for skin disorders caused by anti-epidermal growth factor receptor (EGFR) antibody drugs is limited.The aim of this study was to analyse the factors associated with skin disorders caused by anti-EGFR antibody drugs and establish a method to minimize such aggravations. Methods:We retrospectively examined 67 colorectal cancer patients treated with anti-EGFR antibody drugs for the first time.Results and discussion: A higher proportion of males than females experienced drug withdrawal, dose reduction or treatment discontinuation. The multiple logistic regression analysis revealed body weight as a risk factor affecting drug withdrawal, dose reduction or treatment discontinuation because of an acneiform rash. An examination of methods to avoid the aggravation of skin disorders revealed the acneiform rash grade in patients who received prophylactic minocycline was significantly lower than that in patients who did not receive prophylactic minocycline. Furthermore, among patients with grade 1 acneiform rash at the initiation of minocycline, the proportion of those who withdrew, required dose reduction or discontinued treatment was lower than that among patients with grade 2 acneiform rash. What is new and Conclusion:High body weight was identified as a novel factor for skin disorder aggravation caused by anti-EGFR antibody drugs. The aggravation of skin disorders during cancer treatment with anti-EGFR antibody drugs can potentially be avoided by carefully observing the onset of acneiform rash in affected patients with high body weight and using minocycline prophylactically or as an early-stage intervention.

Effect of risk factors for acneiform rash induced by anti-epidermal growth factor receptor antibody drugs on survival: a retrospective observational study

“…The target patients were classified into two groups based on body weight, extracted as a risk factor from our previous report [ 11 ]. Patient characteristics for each group, classified by body weight, are shown in Table 2 .…”

“…Patients with skin diseases, including psoriasis or atopic dermatitis, were excluded from the study. This study included patients who were previously enrolled in a study that identified high body weight as a risk factor for developing acneiform rash during anti-EGFR antibody therapy [ 11 ]. Therefore, as in the previous study, the target patients were classified based on body weight, which was the risk factor for developing acneiform rash.…”

“…For example, male or young patients with colorectal cancer (CRC) treated with cetuximab, an anti-EGFR antibody drug, are at an increased risk of developing grade 2–3 acneiform rash [ 10 ]. Additionally, we previously reported high body weight as a risk factor for developing acneiform rash caused by anti-EGFR antibody drugs [ 11 ]. However, the effect of body weight on survival probability remains unclear.…”

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

“…A phase III clinical trial conducted in Canada in 2016 showed that the preventive use of minocycline (100 mg twice a day for 1 month) before erlotinib did not reduce the incidence of rashes but reduced the incidence of grade 3 skin toxicity while not affecting efficacy ( 177 ). Takahashi et al ( 120 ) also showed that the grade of acneiform rash was lower after preventive use of minocycline. Meanwhile, Ichiki et al ( 178 ) found that prophylactic use of minocycline (50 mg twice a day for 4 weeks) reduced rashes and paronychia induced by afatinib.…”

“…Another study showed that patients with high sebaceous gland activity and sebum secretion were more sensitive to EGFR inhibitors and developed acneiform rash more frequently (119). Takahashi et al (120) also found that men and high-weight patients who used EGFR inhibitors were more susceptible to severe skin toxicity. High male hormones, high sebum secretion, and smoking (more prevalent in males than females) are risk factors causing male lung cancer patients to have more severe adverse skin reactions.…”