Table 3.

Randomized trial for EGFR-TKI-associated skin rash

Author	EGFR-TKIs	Intervention	Study drug	Observation	Patients (n)	Primary endpoints	Secondary endpoints	Results	References
Arrieta et al.	Afatinib	Preventive	Tetracycline 250 mg twice a day	4 weeks	90	Incidence of toxicity	Dose reduction rate Anti-tumour efficacy	Skin rash (all grades) 75.5% (control) 55.5% (preemptive) (P = 0.046) Skin rash (grade ≥2) 35.6% (control) 15.6% (preemptive) (P = 0.030)	(63)
Melosky et al.	Erlotinib	Preventive	Minocycline 100 mg twice a day	Until PD	150	Time to occurrence and incidence of rash	Survival	Rash (grade 3) 12%* (prophylactic) 8%** (reactive) 28% (control) Mean (days) to any rash onset 17.4 days*** (prophylactic) 13.3 days (reactive) 12.0 days (control)	(64)

EGFR-TKI, epidermal growth factor receptor-tyrosine kinase inhibitor; PD, progressive disease.

^*P = 0.0455 (prophylactic vs. control).

^**P = 0.0092 (reactive vs. control).

^***P = 0.0147 (prophylactic vs. combined reactive and control).