Tetracycline to prevent epidermal growth factor receptor inhibitor‐induced skin rashes

Abstract

PURPOSE Epidermal growth factor receptor inhibitors are effective cancer therapies, but they cause a rash in greater than 50% of patients. This study tested tetracycline for rash prevention. METHODS This placebo-controlled, double-blinded trial enrolled patients who were starting cancer treatment with an epidermal growth factor receptor inhibitor. Patients could not have had a rash at enrollment. All were randomly assigned to either tetracycline 500 milligrams orally twice a day for 28 days versus a placebo. Patients were monitored for rash (monthly physician assessment and weekly patient-reported questionnaires), quality of life (SKINDEX-16), and adverse events. Monitoring occurred during the 4-week intervention and then for an additional 4 weeks. The primary objective was to compare the incidence of rash between study arms, and 30 patients per arm provided a 90% probability of detecting a 40% difference in incidence with a p-value of 0.05 (2-sided). RESULTS Sixty-one evaluable patients were enrolled, and arms were well balanced on baseline characteristics, rates of drop out, and rates of discontinuation of the epidermal growth factor receptor 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). Tetracycline appears to have lessened rash severity, although high drop out rates invite caution in interpreting findings. By week 4, physician-reported grade 2 rash occurred in 17% of tetracycline-treated patients (n=4) and in 55% of placebo-exposed patients (n=16); (p=0.04). Tetracycline-treated patients reported better scores, as per the SKINDEX-16, on certain quality of life parameters, 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 epidermal growth factor receptor inhibitor-induced rashes and cannot be clinically recommended for this purpose. However, preliminary observations of diminished rash severity and improved quality of life suggest this antibiotic merits further study.

Cetuximab Therapy of Metastasizing Cutaneous Squamous Cell Carcinoma in a Patient with Severe Recessive Dystrophic Epidermolysis Bullosa

“…Tetracycline possesses anti-inflammatory properties, which probably underlie the therapeutic mechanisms. Prevention of skin rash by initiating tetracycline concomitantly with anti-EGFR therapy failed in one study [11]. …”

Skin problems and EGFR-tyrosine kinase inhibitor

“…There were several reports that the efficacy of systemic tetracycline, doxycycline or minocycline was evaluated for the treatment or prophylaxis for the EGFR inhibitor-associated skin rash (60)(61)(62)(63)(64). Topical nadifloxacin cream was also evaluated for the treatment of cetuximab-induced skin rash in the uncontrolled prospective study (65).…”

Clinical Predictors of Severe Cetuximab-Induced Rash: Observations from 933 Patients Enrolled in North Central Cancer Treatment Group Study N0147

“…Cutaneous pain and hypersensitivity, worries about appearance, and frustration from having to contend with this side effect – all detract from cancer patients’ quality of life and translate into substantial morbidity [4]. This morbidity is all the more concerning because of limited preventive and palliative options [1,5,6,7]. …”