Background: The EGFRIs and TKIs are effective for cancer target therapy, but the acneiform rashes or called inflammatory papulopustular exanthemas are common (50% to 100%). The conventional therapy for EGFRIs/TKIs-induced skin toxicity is steroids and antibiotics, but their effect is still limited. In this study, a modified Chinese herbal medicine Huang Lian Jie Du decoction cream with Yin-Cold (YC) medicine characteristic was investigated for the effect on patients suffering EGFRIs/TKIs-induced skin toxicity.Methods: The modified Huang Lian Jie Du (mHLJD) decoction cream was made from 10 herbal medicines including 4 major medicines (Huanglian, Huangqin, Huangbo, and Zhizi) in traditional HLJD decoction. Patients with EGFRIs/TKIs-induced skin toxicity were enrolled. Patients were excluded if they also used other cream for the skin toxicity. Skin conditions were follow up every 2 weeks. The patients’ characteristics, the skin toxicities and treatment response were recorded and analyzed after using mHLJD decoction cream for 1~2 months.Results: The mHLJD decoction cream and its subpackages were stored at 4℃ before use. Thirty-four patients who had grade 1-3 skin toxicities after receiving EGFRIs or TKIs were enrolled. Five patients were withdrawal or excluded, 2 patients with paronychia syndrome had no improvement and were excluded, too. Finally, data from 27 patients were analyzed. The mean grade of rash acneiform was decreased from 2.23 (ranged 1 to 3) to 0.38 (ranged 0 to 1) after mHLJD decoction cream treatment for 1~2 months. And the mean grade of dry skin was decreased from 1.57 (ranged 1 to 2) to 0.77 (ranged 0 to 1). The changes of skin toxicity were significant and no obvious adverse events.Conclusions: In summary, the mHLJD decoction cream is effective for alleviation of EGFRIs/TKIs-induced skin rash acneiform and dry skin. And mHLJD decoction cream has no effect in patients with paronychia syndrome.Trial registration: CYCH, CYCH-IRB No. 2019023. Registered 14 May 2019, http://www.cych.org.tw/irbweb/

Background. The EGFRIs and TKIs are effective for cancer target therapy, but the acneiform rashes or called inflammatory papulopustular exanthemas are common (50% to 100%). The conventional therapy for EGFRIs/TKIs-induced skin toxicity is steroids and antibiotics, but their effect is still limited. In this study, a modified Chinese herbal medicine Huang Lian Jie Du decoction cream with Yin-Cold (YC) medicine characteristic was investigated for the effect on patients suffering EGFRIs/TKIs-induced skin toxicity.Methods. The modified Huang Lian Jie Du (mHLJD) decoction cream was made from 10 herbal medicines including 4 major medicines (Huanglian, Huangqin, Huangbo, and Zhizi) in traditional HLJD decoction. Patients with EGFRIs/TKIs-induced skin toxicity were enrolled. Patients were excluded if they also used other cream for the skin toxicity. Skin conditions were follow up every 2 weeks. The patients’ characteristics, the skin toxicities and treatment response were recorded and analyzed after using mHLJD decoction cream for 1~2 months.Results. The mHLJD decoction cream and its subpackages were stored at 4℃ before use. Thirty-four patients who had grade 1-3 skin toxicities after receiving EGFRIs or TKIs were enrolled. Five patients were withdrawal or excluded, 2 patients with paronychia syndrome had no improvement and were excluded, too. Finally, data from 27 patients were analyzed. The mean grade of rash acneiform was decreased from 2.23 (ranged 1 to 3) to 0.38 (ranged 0 to 1) after mHLJD decoction cream treatment for 1~2 months. And the mean grade of dry skin was decreased from 1.57 (ranged 1 to 2) to 0.77 (ranged 0 to 1). The changes of skin toxicity were significant and no obvious adverse events.Conclusions. In summary, the mHLJD decoction cream is effective for alleviation of EGFRIs/TKIs-induced skin rash acneiform and dry skin. And mHLJD decoction cream has no effect in patients with paronychia syndrome.

Background. Epidermal growth factor receptor inhibitors (EGFRIs) and tyrosine kinase inhibitors (TKIs) are key drugs in targeted cancer therapy. However, they may cause skin toxicity. We previously prepared a modified Huang-Lian-Jie-Du (mHLJD) decoction cream using 10 herbs, which effectively alleviated EGFRI/TKI-induced skin toxicity. In the present study, we identified the reference markers of the mHLJD decoction and investigated the anti-inflammatory and antibacterial effects of the mHLJD decoction extract. Methods. We performed high-performance liquid chromatography (HPLC) to determine the composition of the mHLJD decoction. Human epidermoid A431 cells were treated with tumor necrosis factor (TNF)-α to induce inflammation; then, the effects of the mHLJD decoction extract on the cytokine expression were determined using a cytokine array and by performing real-time quantitative polymerase chain reaction (qPCR). The antibacterial effects of the extract were examined using disk diffusion and microdilution assays. Results. HPLC results revealed that the mHLJD decoction primarily consisted of geniposide, berberine chloride, baicalin, coptisine, and palmatine. TNF-α treatment increased the expression of certain cytokines, including IL-1β, IL-8, M-CSF, and TGF-β2; however, pretreatment with the mHLJD decoction extract reduced their expression. The qPCR results demonstrated a decreased mRNA expression of IL-8, M-CSF, and TGF-β2. The antibacterial assay revealed that the extract exerted inhibitory effects on Staphylococcus aureus, forming an inhibition zone at the minimum inhibitory concentrations of 3.125 and 6.25 mg/mL; however, the extract exerted no effects on Escherichia coli and Pseudomonas aeruginosa. Conclusions. We developed an HPLC method to quantify the reference markers of the mHLJD decoction. The bioactivity analysis provided the potential mechanisms underlying the effects of the mHLJD decoction on EGFRI/TKI-induced skin toxicity.