Arrieta, O., Vega-Gonzalez, M.T., Lopez-Macias, D., Martinez-Hernandez, J.N., Bacon-Fonseca, L., Macedo-Perez, E.O., . . . de la Garza-Salazar, J. (2015). Randomized, open-label trial evaluating the preventive effect of tetracycline on afatinib-induced skin toxicities in non-small cell lung cancer patients. Lung Cancer (Amsterdam, Netherlands), 88, 282–288. 

To evaluate the effectiveness of prophylactic tetracycline on afatinib-induced skin toxicities

Afatinib was given after disease progression with chemotherapy. Patients receiving afatinib were randomly assigned to receive general dermatological recommendations (control group) or 250 mg tetracycline every 12 hours in addition to general recommendations. All were receiving 40 mg afatanib every day until disease progression or toxicity. Dosage of afatinib was reduced to 30 mg daily for grade 3 or prolonged grade 2 toxicity. General recommendations provided to all patients were brief baths with lukewarm water, use of sunscreen, emollient creams, hypoallergenic soap, and fingernail care. Study assessments were conducted at baseline, week 2, and week 4 by a blinded assessor.

• N = 90
• MEAN AGE = 57 
• MALES: 26.7%, FEMALES: 73.3%
• KEY DISEASE CHARACTERISTICS: All had lung cancer.

• SITE: Single site  
• SETTING TYPE: Outpatient  
• LOCATION: Mexico

PHASE OF CARE: Active antitumor treatment

• Single-blind, randomized, controlled trial

• National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

Most common toxicities were rash (65.6%), pruritus,(42.2%), mucositis (41.1%), paronychia (33.3%), skin fissures (24.4%), folliculitis (24.4%), and trichomegaly (22.2%). No grade 5 toxicities existed. Rash incidence was 75.5% in the control group versus 55.5% in the tetracycline group (relative risk [RR] = 0.4, p = 0.046), and rash severity of grade 2 or higher was 15.6% in the tetracycline group compared to 35.6% among controls (RR = 0.35, p = 0.03). Incidence of paronychia was lower in the tetracycline group, but group differences were not statistically significant. No other differences existed between groups in skin effects, and no differences existed between groups in the proportion of patients who required afatinib dose reductions. Most patients developed maximum rash intensity between weeks 1 and 4 of treatment. No relationship existed between rash incidence or severity and general disease outcomes.

Prophylactic tetracycline was effective in reducing the incidence and severity of rashes associated with afatinib use.

• Small sample (< 100)

Very limited evidence exists for effective interventions to prevent or treat skin toxicities associated with epidermal growth factor receptor inhibitor (EGFRI) administration. Although the use of antibiotics has been suggested, currently little research demonstrates their efficacy. This study begins to fill that evidence gap, showing that tetracycline can be effective in reducing the incidence and severity of skin toxicity. This is a relatively low-cost and generally safe intervention to reduce adverse skin effects in patients receiving EGFRIs.