CHICAGO — Tetracycline may reduce the severity of rashes associated with epidermal growth factor receptor inhibitors, such as gefitinib and cetuximab, but the antibiotic doesn't seem to prevent such rashes.
More than 75% of patients on epidermal growth factor receptor (EGFR) inhibitors develop an acneiform rash. The rash can be very problematic for patients, said Dr. Aminah Jatoi, a professor of oncology at the Mayo Clinic in Rochester, Minn.
Dr. Jatoi and her colleagues randomized 61 cancer patients to 500 mg oral tetracycline twice daily or placebo twice daily for 1 month. Patients were included if they had started an EGFR inhibitor within 7 days of enrollment and did not have a rash.
“Tetracycline did not prevent EGFR inhibitor-induced rashes. However, diminished rash severity and improved quality of life suggest this antibiotic deserves further study,” Dr. Jatoi said at the annual meeting of the American Society of Clinical Oncology.
Rashes were assessed by physicians and patients over an 8-week period. Physicians submitted monthly reports using the Common Terminology Criteria for Adverse Events v3.0. Patients submitted weekly reports, including the answers to a brief questionnaire on rash incidence (the Skindex-16), and an EGFR inhibitor compliance questionnaire.
A small portion of patients—10% in the treatment arm and 17% in the placebo arm—were being treated with gefitinib. An additional 35% and 40% were being treated with cetuximab in the treatment and placebo arms, respectively. The remaining 55% and 43% were taking other EGFR inhibitors (EGFR tyrosine kinase inhibitors) in the treatment and placebo arms, respectively.
“With regard to the primary end point [rash prevention], this was a negative study,” Dr. Jatoi said. Physician-reported rash incidence was comparable between the two arms at weeks 4 and 8. At week 4, the incidence was 70% and 76% for the treatment and placebo arms, respectively. Likewise at week 8, the incidence was 87% and 84% for the treatment and placebo arms, respectively. Patient-reported results were similar.
In terms of physician-reported rash severity, significantly fewer patients (17%) on tetracycline had rashes with grade 2 or greater at 4 weeks, compared with those on placebo (55%). However, the difference was not significant at 8 weeks—27% in the tetracycline group vs. 47% in the placebo group. Patient-reported results were similar.
Patients on tetracycline did report less itching on the Skindex-16 starting at week 2, however.
Three patients in each arm stopped taking EGFR inhibitors early because of cancer-related issues. Adverse events were comparable in both treatment arms.
“We invite caution, however, in interpreting these results for two reasons. First, this was a secondary end point not a primary end point. Secondly, the numbers are very small. Dropout rates were quite high over time,” Dr. Jatoi said.
The issue of EGFR inhibitor-induced rash is particularly troublesome for patients, because it has been suggested that the presence of skin rash may be associated with tumor response.
“Patients are sometimes finding themselves in quandary. They're getting a severe rash and it bothers them. Yet at the same time they're saying, 'My tumor may well be responding to this drug. I can't stop taking this drug and yet I want to,'” Dr. Jatoi said.