Gerber, P.A., Meller, S., Eames, T., Buhren, B.A., Schrumpf, H., Hetzer, S., ... Homey, B. (2012). Management of EGFR-inhibitor associated rash: A retrospective study in 49 patients. European Journal of Medical Research, 17(1), 4.  

To compare the effectiveness of three established rash-management strategies in EGFR-inhibitor (EGFRI) associated rash development

Rash severity was assessed during the initial presentation to clinic by applying the EGFR-Induced Rash Severity Score (ERSS). Three different EGFRI rash-management strategies were compared, and each targeted the inflammatory and/or the infectious characteristics of the rash. In stage 1 of the study, 21 patients (ERSS 10.3 to 77.9) were treated topically with mometasone furoate cream (a topical anti-inflammatory) twice daily. In stage 2 of the study, 23 patients (ERSS 12.5 to 67.1)  were treated topically with nadifloxacin 1% cream (a potent topical fluoroquinolone antibiotic) once daily in the morning, in combination with prednicarbate 0.25% cream (a topical glucocorticosteroid) once daily in the evening. In stage 3 of the study, five patients (ERSS > 50) received topical nadifloxacin and prednicarbate 0.25% cream in combination with the systemic retinoid isotretinoin 10–20 mg/day. Rash severity was reassessed after three weeks of specific therapy to manage the dermatologic reaction.

• N = 49            
• AGE = Not reported
• MALES: Not reported, FEMALES: Not reported
• KEY DISEASE CHARACTERISTICS: Not reported
• OTHER KEY SAMPLE CHARACTERISTICS: (1) DRUG: Patients who were treated with either cetuximab (a monoclonal anti-EGFR antibody) or erlotinib (a small molecule EGFR tyrosine kinase inhibitor), and who developed an EGFRI-associated rash at the time of referral to the physician’s clinic. (2) TIMING: Selection was limited to initial patients, and their follow-up visits were made in the timeframe of March 2007 to October 2009. (3) RASH SEVERITY: Patients who presented with ERSS of 10 or higher.  

• SITE: Multi-site      
• SETTING TYPE: Outpatient          
• LOCATION: Germany

• PHASE OF CARE: Active antitumor treatment

Retrospective, uncontrolled, comparative study

Patients' EGFRI-associated rash severity improved significantly with all three dermatological treatments, which are aligned with recent expert recommendations: topical mometasone furoate cream (p = 0.00009); nadifloxacin 1% cream and prednicarbate 0.25% cream (p = 0.03); and nadifloxacin 1% cream and prednicarbate 0.25% cream plus systemic isotretinoin (p = 0.015).

In summary, the results demonstrate that EGFRI-associated rashes can be effectively managed by specific dermatologic interventions, including topical glucocorticosteroids, topical antiseptics/antibiotics, and systemic retinoids. Topical mometasone furoate cream was the only therapy that resulted in a complete resolution of all rash symptoms in one patient.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)  
• Risk of bias (no random assignment)
• Other limitations/explanation
  • For the sample population, age, sex, and diagnosis were not reported.
  • Statistical comparison of different therapy regimens is limited due to variations in patient numbers and rash severity in each of the three test groups before therapy. Specifically, group 3 had only five patients and the rash severity in all five patients was ERSS > 50 (severe).
  • The study design did not include a control group, which would have been a subgroup of patients with EGFRI rash that was left untreated for the study period (three weeks).
  • In the abstract, the authors state that mild to moderate rashes should be treated with basic measures in combination with other dermatologic treatments. In the discussion section, the authors state, “Notably, all approaches that were analyzed in this study are in line with recent expert recommendations that suggest an escalating strategy for the management of the EGFRI rash with a succession of treatments, as indicated, summarized as follows: intensive skin care in combination with mild cleansers ... .”   The components of “basic measures” or “intensive skin care” were not described, and whether intensive skin care and mild cleansers were included with the other interventions is not delineated in the article.
  • The ERSS system was designed with a non-linear affected area scale emphasizing minor variations in mild patients with face involvement only.   

Nurses should consider treating mild to moderate EGFRI skin rashes with basic skin care measures in combination with topical glucocorticosteroids or combined regimens using glucocorticosteroids and antiseptics/antibiotics. Nurses should be aware that more severe or therapy-resistant rashes may respond with the addition of systemic retinoids.