Topical doxycycline foam 4% for prophylactic management of epidermal growth factor receptor inhibitor skin toxicity: an exploratory phase 2, randomized, double-blind clinical study

• Published in: Supportive care in cancer Vol. 27; no. 8; pp. 3027 - 3033
• Main Authors: Shacham Shmueli, Einat, Geva, Ravit, Yarom, Nirit, Hubert, Ayala, Keynan, Rita, Kedem, Tal H., Eini, Meir, Tamarkin, Dov, Shirvan, Mitchell
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2019; Springer; Springer Nature B.V
• Subjects: Antibiotics; Cancer; Care and treatment; Chemotherapy; Clinical trials; Colorectal cancer; Dermatitis; Double-blind studies; Doxycycline; Epidermal growth factor; Medicine; Medicine & Public Health; Metastasis; Monoclonal antibodies; Nursing; Nursing Research; Oncology; Original Article; Pain Medicine; Panitumumab; Patient safety; Rehabilitation Medicine; Side effects; Skin; Targeted cancer therapy; Toxicity; Acneiform rash; Topical doxycycline foam; FDX104; Epidermal growth factor inhibitor; Skin toxicity; Colorectal cancer
• ISSN: 0941-4355; 1433-7339; 1433-7339
• DOI: 10.1007/s00520-018-4600-8

Purpose Acneiform rash, a common toxicity of epidermal growth factor receptor inhibitors (EGFRIs), can cause patient discomfort, warranting changes in treatment. This study investigated the safety, tolerability, and efficacy of a novel doxycycline foam, FDX104 4%, for managing EGFRI-related skin toxicity. Methods This was an exploratory phase 2, randomized, double-blind, placebo-controlled study. Subjects had metastatic colorectal cancer and were being treated with either cetuximab or panitumumab plus chemotherapy. Treatment (twice-daily topical FDX104 4% on one side of the face and vehicle foam on the other for 5 weeks) was initiated 7 ± 3 days prior to EGFRI therapy. Rash severity, safety, and tolerability were evaluated at 2 and 4 weeks after EGFRI start. Results The mean maximal rash grade was lower with FDX104 4% vs vehicle, and fewer subjects developed moderate-to-severe (grades 2–3) rash. On the Global Severity Score scale, a statistically significant difference favored FDX104 4% over vehicle ( P  = .047). Adverse events (AEs) ( n  = 68) occurred in 20 subjects; most were mild or moderate. The most common AEs were oral mucositis, nausea, and vomiting, common to chemotherapy and EGFRI treatment. Study-drug–related AEs were experienced by five subjects and consisted of mild, local skin reactions. No study-drug–related systemic side effects were reported. Conclusion Twice-daily, topical administration of FDX104 4% as an adjunct to either cetuximab or panitumumab was safe and well tolerated, and appeared to prevent the onset of rash, especially severe rash. ClinicalTrials.gov identifier Trial Registration NCT02239731