Deplanque, G., Gervais, R., Vergnenegre, A., Falchero, L., Souquet, P.J., Chavaillon, J.M., . . . Chosidow, O. (2016). Doxycycline for prevention of erlotinib-induced rash in patients with non-small-cell lung cancer (NSCLC) after failure of first-line chemotherapy: A randomized, open-label trial. Journal of the American Academy of Dermatology, 74, 1077–1085. 

To evaluate the efficacy of doxycycline in the prevention of erlotinib-induced rash (folliculitis) in patients with non-small cell lung cancer (NSCLC)

Patients were randomized via a computer website to receive either erlotinib 150 mg/d per os or erlotinib 150 mg/d per os plus 100 mg/d of doxycycline. Doxycycline began on day 0 (day of randomization) and was continued for four months and as long as 12 months at the primary investigator's discretion. Erlotinib began on day 1 and was administered for as long as 12 months or beyond or until disease progression or intolerable toxicity. Patients were evaluated on days 14 and 28 and at months 2, 4, 7, 10, and 12. Patients with grade 2 or higher folliculitis received treatment as appropriate.

• N = 147   
• MEAN AGE = 64 years (SD = 11)
• MALES: 67%, FEMALES: 33% 
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Patients with NSCLC 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients being treated with erlotinib, patients aged 18 years or older, patients with histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IIIB/IV) NSCLC, patients who had failed first-line platinum-based chemotherapy, measurable disease was according to response Evaluation Criteria in Solid Tumors, patients who had an Eastern Cooperative Oncology Group (ECOG) performance status of less than 2 (e.g., scale from 0 [fully active] to 4 [completely disabled]), patients who had adequate organ function and an estimated life expectancy of 12 weeks or longer

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Lausanne, Switzerland, and 23 sites in France

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care

Open-label, randomized, prospective, phase II trial

• Skin efficacy—anonymous photographs were analyzed by a committee of blinded expert dermatologist using Common Terminology Criteria for Adverse Events (CTCAE) grading.
• Tumor response—Response Evaluation Criteria in Solid Tumors (RECIST)
• Quality of life—Dermatology Life Quality Index (DLQI)
• Compliance—daily doses of erlotinib and doxycycline were collected at each study time point.
• Adverse events—graded according to CTCAE, version 3.0

FOLLICULITIS: During the first four months of treatment, 52 patients (71%) in the doxycycline arm and 59 patients (81%) in the control arm developed folliculitis (p = 0.18). The mean duration of folliculitis was similar in both treatment arms (no p value given). Sixty-two percent of patients in the intervention arm developed grade 1 folliculitis compared to 19% in the control arm. Grade 3 folliculitis developed in 4% of patients in the intervention arm and 19% in the control arm (p < 0.001).

Doxycycline did not reduce the incidence of erlotinib-induced folliculitis but significantly reduced its severity. In fact, more patients in the intervention arm developed grade 1 folliculitis compared to the control arm. The duration of folliculitis was similar in both the intervention and control arm in this study. Compliance with erlotinib was higher in the doxycycline arm during the whole treatment period.

• Risk of bias (sample characteristics)
• Risk of bias (due to open label)
• More males than females in study
• The authors did not report on possible statistical differences in sample characteristics.

Nurses can collaborate with physicians to verify that doxycycline is combined with erlotinib treatment to improve the level of toxicity of folliculitis. Doxycycline has the potential to decrease the severity of folliculitis in patients with NSCLC who are receiving erlotinib. It does not, however, reduce the incidence of folliculitis in these patients during the first four months of treatment with erlotinib, nor does it reduce the duration of folliculitis.