title: 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).
abstract: 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.
authors.affiliation: Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA. Jatoi.aminah@mayo.edu
authors.forename: Aminah
authors.initials: A
authors.lastname: Jatoi
authors.forename: Shaker R
authors.initials: SR
authors.lastname: Dakhil
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Sloan
authors.forename: John W
authors.initials: JW
authors.lastname: Kugler
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: Paul L
authors.initials: PL
authors.lastname: Schaefer
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Novotny
authors.forename: Donald B
authors.initials: DB
authors.lastname: Wender
authors.forename: Howard M
authors.initials: HM
authors.lastname: Gross
authors.forename: Charles L
authors.initials: CL
authors.lastname: Loprinzi
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D013752:Tetracycline
references.citation: N Engl J Med. 2005 Jul 14;353(2):123-32
references.pmid: 16014882
references.citation: J Clin Oncol. 2004 Apr 1;22(7):1201-8
references.pmid: 14993230
references.citation: J Am Acad Dermatol. 1986 Feb;14(2 Pt 1):183-6
references.pmid: 2936772
references.citation: Oncology (Williston Park). 2007 Oct;21(11 Suppl 5):34-6
references.pmid: 18154217
references.citation: Oncologist. 2008 Nov;13(11):1201-4
references.pmid: 18988655
references.citation: Cancer. 2008 Aug 15;113(4):847-53
references.pmid: 18543329
references.citation: J Cutan Med Surg. 2001 Mar-Apr;5(2):105-10
references.pmid: 11443481
references.citation: J Clin Oncol. 2007 Dec 1;25(34):5390-6
references.pmid: 18048820
references.citation: Clin Lung Cancer. 2008 Jan;9(1):59-60
references.pmid: 18282360
references.citation: Dermatology. 1998;196(1):135-9
references.pmid: 9557248
references.citation: J Drugs Dermatol. 2009 Mar;8(3):274-5
references.pmid: 19271376
references.citation: JOP. 2009 May 18;10(3):338-40
references.pmid: 19454833