Does tetracycline prevent/palliate epidermal growth factor receptor (EGFR) inhibitor-induced rash? A phase III trial from the North Central Cancer Treatment Group (N03CB)
LBA9006 Purpose: Many patients who receive EGFR inhibitors develop an acneiform rash, and anecdotal reports suggest tetracycline is effective in treating it. To our knowledge, however, no rigorous trials have ever been published to substantiate this approach. This double- blinded, placebo-controlled trial was conducted to assess the role of tetracycline in preventing EGFR inhibitor-induced rash and/or reducing its severity. Methods: 61 patients were randomly assigned to tetracycline 500 mg orally twice a day×4 weeks versus an identical, similarly prescribed placebo. Eligibility criteria required all patients to have begun an EGFR inhibitor </= 7 days prior with no rash at study entry. Patients were to be followed for 8 weeks. Physician assessments of rash incidence, severity, and adverse events, occurred at 4 and 8 weeks. Patients completed a weekly rash diary, quality of life questionnaire (SKINDEX-16), and EGFR inhibitor compliance questionnaire. Thirty patients per group provides 90% power to detect a difference in rash incidence (the primary endpoint) of 40% between groups and of rejecting the null hypothesis of equal proportions with a type I error of 5% (2-sided). Results: Treatment arms were balanced on baseline characteristics, drop out rates, and rates of discontinuation of the EGFR inhibitor. Rash incidence was comparable across arms. Physicians reported that 16 tetracycline-treated patients (70%) and 22 placebo-exposed patients (76%) developed a rash (p=0.61). However, tetracycline appears to have lessened rash severity. By week 4, physician-reported grade 2 rash occurred in 17% of tetracycline-treated patients (n=4) and 55% of placebo- exposed patients (n=16); (p=0.04). Tetracycline-treated patients reported better scores on certain quality of life parameters (SKINDEX-16), such as skin burning or stinging, skin irritation, and being bothered by a persistence/recurrence of a skin condition. Adverse events were comparable across arms. Conclusion: Tetracycline did not prevent EGFR inhibitor-induced rashes. However, diminished rash severity and improved quality of life suggest this antibiotic merits further study. No significant financial relationships to disclose.