JMIR Publications

ABSTRACT

Background:

Epidermal growth factor receptor inhibitors (EGFRIs) are widely used in targeted therapy for various malignant tumors. However, these agents frequently cause adverse effects on the skin and its appendages, with skin toxicity being the most common, occurring in 79%–88% of patients. This severely reduces patients’ quality of life and adherence to anticancer treatment. Currently, there is a lack of well-evidenced preventive interventions. Xiaozhen Formula (XZF), composed of seven Chinese herbal medicines, has the effects of clearing heat and detoxifying, eliminating dampness and resolving nodules, cooling blood and promoting eruption. Preliminary clinical practice shows promising efficacy in preventing EGFRI-related skin toxicity, but high-quality clinical trial evidence remains insufficient.

Objective:

This study aims to evaluate the efficacy and safety of XZF in preventing EGFRI-induced skin toxicity through a multicenter, randomized, double-blind, placebo-controlled clinical trial, with a focus on its effect on the incidence of rash.

Methods:

This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. Eligible participants are patients with malignant tumors aged 18–75 years, scheduled to receive or initially receiving EGFRI therapy with a planned treatment duration of at least 8 weeks. Patients will be randomized 1:1 into the treatment group and the control group. Both groups will receive standard EGFRI therapy. The treatment group will additionally receive oral XZF, while the control group will receive a placebo identical to XZF in appearance, formulation, and administration. The intervention will last 8 weeks. The primary outcome is the incidence of rash during EGFRI treatment, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Secondary outcomes include the incidence of grade ≥2 rash, time to first onset of rash, rash severity, dermatology-related quality of life, adherence to EGFRI therapy, and adverse events. Both intention-to-treat (ITT) and per-protocol (PP) analyses will be conducted, with a two-sided significance level of α=0.05.

Results:

Compared with placebo, XZF is expected to significantly reduce the incidence of EGFRI-related rash and the proportion of moderate-to-severe rash, delay the onset of rash, and demonstrate a favorable safety profile.

Conclusions:

This study will provide high-quality evidence for the role of traditional Chinese medicine in preventing EGFRI-induced skin toxicity, improve the management system for adverse reactions to targeted cancer therapy, and offer a new treatment option for comprehensive cancer care, thereby enhancing patient adherence and quality of life. Clinical Trial: This study has been registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2500095160) and has received ethical approval from the Ethics Committee of the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine (approval number: 2022-LWKY-027) and the ethics committees of other participating hospitals.