Prophylactic tetracycline does not diminish the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash: results from the North Central Cancer Treatment Group (Supplementary N03CB).
OBJECTIVE
Previous studies suggest tetracycline and other antibiotics lessen the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash. This study sought to confirm such findings.


METHODS
Patients starting an EGFR inhibitor were eligible for this randomized, double-blinded, placebo-controlled study and had to be rash-free. They were then randomly assigned to tetracycline 500 mg orally twice a day for 28 days versus a placebo. Rash development and severity (monthly physician assessment and weekly patient-reported questionnaires), quality of life (SKINDEX-16), and adverse events were monitored during the 4-week intervention and then for an additional 4 weeks. The primary objective was to compare the incidence of grade 2 or worse rash between study arms; 32 patients per group provided a 90% probability of detecting a 40% difference in incidence with a type I error rate of 0.05 (two-sided).


RESULTS
Sixty-five patients were enrolled, and groups were balanced on baseline characteristics. During the first 4 weeks, healthcare provider-reported data found that 27 tetracycline-treated patients (82%) and 24 placebo-exposed patients (75%) developed a rash. This rash was a grade 2+ in 17 (52%) and 14 (44%), respectively (p = 0.62). Comparable grade 2+ rash rates were observed during weeks 5 through 8 as well as with patient-reported rash data throughout the study period. Quality of life was comparable across study arms, and tetracycline was well tolerated.


CONCLUSIONS
Although previous studies suggest otherwise, this randomized, double-blinded, placebo-controlled study did not find that tetracycline lessened rash incidence or severity in patients who were taking EGFR inhibitors.
Jatoi
Aminah
A
Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA. Jatoi.aminah@mayo.edu
Dakhil
Shaker R
SR
Sloan
Jeff A
JA
Kugler
John W
JW
Rowland
Kendrith M
KM
Schaefer
Paul L
PL
Novotny
Paul J
PJ
Wender
Donald B
DB
Gross
Howard M
HM
Loprinzi
Charles L
CL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000209:etiology / Q000517:prevention & control*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012720:Severity of Illness Index; D013752:Tetracycline / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D013752:Tetracycline
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