Jatoi, A., Thrower, A., Sloan, J.A., Flynn, P.J., Wentworth-Hartung, N.L., Dakhil, S.R., . . . Loprinzi, C.L. (2010). 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, 15, 1016–1022.

To determine whether sunscreen prevents or mitigates epidermal growth factor receptor–inhibitor (EGFRI)-induced rashes.

Patients were stratified based on (a) first-line cancer therapy versus other therapy, (b) type of EGFRI prescribed or anticipated (e.g., small molecule inhibitor versus monoclonal antibody), and (c) use of a concurrent medication that increases sun hypersensitivity.   

Patients were randomly assigned to sunscreen with a sun protection factor (SPF) of 60 to be applied to the face, trunk, and extremities BID for 28 days versus an identical-appearing  placebo. The sunscreen included 7.5% titanium dioxide and 7.5% zinc oxide, and was shown to block more than 90% of both ultraviolet A and ultraviolet B light in preclinical trials. All patients were instructed to stay indoors or in a covered area from 10 AM to 3 PM to avoid peak sun exposure. 

• The study reported on a final sample of 89 patients. Initially, 54 patients were in the sunscreen arm and 56 patients were in the placebo arm.
• Median patient age was 63 years (range 36–90) in the sunscreen arm and 62 years (range 37–88) in the placebo arm.
• The sample was 54% female and 46% male in the sunscreen arm, and 52% female and 48% male in the placebo arm.
• In the sunscreen arm, 22 patients (41%) had lung cancer, 22 patients (41%) had gastrointestinal cancer, and 10 patients (19%) had another type of cancer. In the placebo arm, 17 patients (30%) had lung cancer, 23 patients (41%) had gastrointestinal cancer, and 16 patients (29%) had another type of cancer.
• EGFRI characteristics were as follows. In the sunscreen arm, 21 patients (39%) received erlotinib (or another small molecule inhibitor) and 33 patients (61%) received cetuximab (or another antibody). In the placebo arm, 22 patients (39%) received erlotinib (or another small molecule inhibitor), and 34 patients (61%) received cetuximab (or another antibody).

• Multi-site
• Outpatient clinic
• United States

Patients were undergoing the active treatment phase of care.

This was a placebo-controlled, double-blind trial.

• History and physical (baseline, end of week 4, and end of week 8)
• Performance status score (baseline, end of week 4, and end of week 8)
• Brief rash incidence questionnaire (weekly for eight weeks)
• Skindex-16 (quality-of-life tool) (weekly for eight weeks)
• Previously used questionnaire on patient compliance with EGFRI therapy (weekly for eight weeks)
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (end of week 4 and end of week 8)

• During the four-week intervention, physician-reported rash occurred in 38  patients (78%) in the sunscreen arm and 39 patients (80%) in the placebo arm (p = 1.00). No statistically or clinically significant differences existed in physician-reported rash severity or patient-reported outcomes of rash. Adjustments for sun intensity by geographical zone, season, and use of photosensitivity medication did not yield a significant difference in rash across the study arms (p = 0.2). 
• The patient-reported Skindex-16 questionnaire did not reveal major differences between the study arms. Quality-of-life scores declined but remained comparable between arms. 
• The sunscreen was well tolerated with low and almost identical rates of adverse events in the two study arms.
   

The use of sunscreen (SPF of 60) did not prevent or decrease the severity of EGFRI-induced rash.

• The sample size was fewer than 100 patients. 
• No tool was available to measure the actual degree of sun exposure for each patient.  
• The generalizability of the results is limited. This study primarily included patients who were receiving erlotinib or cetuximab. Other small molecule inhibitors (e.g., lapatinib) and monoclonal antibodies (e.g., panitumumab) exist, and patients receiving those drugs might respond to sunscreen differently.
• Patients were not to be in the sun from 10 AM to 3 PM, so their sun exposure was greatly limited. In addition, actual patient compliance with avoidance of sun exposure and application of sunscreen or placebo was not evaluated or reported.

No evidence existed to support the use of sunscreen to prevent or decrease the severity of EGFRI-induced rash.