Traditional Chinese medicine in the era of immune checkpoint inhibitor: theory, development, and future directions.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer management and have been widely applied; however, they still have some limitations in terms of efficacy and toxicity. There are multiple treatment regimens in Traditional Chinese Medicine (TCM) that play active roles in combination with Western medicine in the field of oncology treatment. TCM with ICIs works by regulating the tumor microenvironment and modulating gut microbiota. Through multiple targets and multiple means, TCM enhances the efficacy of ICIs, reverses resistance, and effectively prevents and treats ICI-related adverse events based on basic and clinical studies. However, there have been few conclusions on this topic. This review summarizes the development of TCM in cancer treatment, the mechanisms underlying the combination of TCM and ICIs, existing studies, ongoing trials, and prospects for future development.

Application of Zizao Yangrong Granules for Treating Targeted Drugs-Related Skin Xerosis: A Randomized Double-Blinded Controlled Study.

Background: Dermatologic toxicities are the most common side effects associated with the targeted drugs epidermal growth factor receptor inhibitors (EGFRIs), in which xerosis commonly complicated by pruritus severely disturbs the quality of life. The study has observed the curative effect of Zizao Yangrong granules (ZYG) from Chishui Xuanzhu in the treatment of EGFRIs-related xerosis and pruritus, as well as evaluating the safety of the prescription. Methods: Patients (n = 68) who had xerosis after using EGFRIs were enrolled and then randomly divided into the treatment group and control group, respectively, receiving ZYG and placebo granules combined with vitamin E ointment. The intervention lasted 4 weeks. Changes in xerosis and pruritus were observed, and blood routine examination as well as liver and kidney function are observed as safety indexes. The water content of skin and qualify of life were observed. Results: A total of 66 out of 68 patients finished the study with 34 patients in each group. The effective rates of xerosis among the treatment group and control group were 84.8% and 69.7% after 2 weeks' treatment (P < .05), while they were 84.8% and 75.8% after 4 weeks' treatment (P < .05). The patients in the experimental group had better quality of life than that in the control group (P = .045). Conclusion: ZYG can effectively improve the skin dryness associated with EGFRIs, and significantly improve the quality of life of patients with good safety; however, larger randomized controlled trials are needed to verify these findings.

Treatment of severe rash caused by crizotinib with both traditional Chinese medicine and Western medicine: Two case reports and literature review.

RATIONALE: Lung adenocarcinoma is the most common pathologic pattern of lung cancer. During the past decades, a number of targeted agents have been explored to treat advanced lung adenocarcinoma. Recently, Crizotinib, the antagonist of anaplastic lymphoma kinase (ALK), has been widely used in ALK-rearranged lung cancer treatment. Crizotinib is generally well tolerated while its most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac and endocrine abnormalities. Rash caused by crizotinib is rarely seen, and there are few case reports of severe rash caused by crizotinib. PATIENT CONCERNS AND DIAGNOSES: Here we report cases of an 81-year-old man and a 66-year-old woman with ALK-rearranged advanced lung adenocarcinoma. When patients came to our department, they both had crizotinib-induced severe rash. INTERVENTIONS: Crizotinib was initiated as the 1st-line treatment without other therapies. We treated severe rash with traditional Chinese medicine (TCM) therapy called Zhiyang Pingfu liquid along with Western medicine. Zhiyang Pingfu liquid consists of Scutellaria baicalensis 20 g, Portulaca oleracea 30 g, Cortex Dictamni 30 g, Sophora flavescens 30 g, and other substances. Western medicine includes Minocycline hydrochloride tablets and Aprepitant capsules. OUTCOMES: Both patients achieved a partial response when treated with crizotinib, and suffered from severe rash. With Zhiyang Pingfu liquid and Western medicine, their rash gradually disappeared with no sign of cancer progression. Also the male patient did not relieve after taking only antibiotics (standard therapy) and anti-allergic medicine. LESSONS: Despite the dramatic benefit of crizotinib for patients with ALK rearrangement, crizotinib-induced severe rash needs to be dealt with caution. This is the 1st case in which TCM and Western medicine are used to successfully treat crizotinib-induced severe rash. The mechanism of crizotinib-induced rash deserves further attention in future research.

[Treatment of EGFRIs-related Skin Adverse Reactions by Zhiyang Pingfu Lotion].

Objective To observe the curative effect of Zhiyang Pingfu Lotion (ZPL) for its ex- ternal application in treatment of epidermal growth factor receptor inhibitors (EGFRIs)-related acneiform rash, cutaneous pruritus , xerosis cutis , and nail changes , as well as to evaluate its safety and patients' satisfaction. Methods Recruited were 201 patients with confirmed pathological diagnosis, who had acne- iform rash after using EGFRIs. They were assigned to the treatment group (131 cases) and the control group (70 cases) by random digit table. Patients in the treatment group were externally applied with self- formulated ZPL based on principles of Western medical standards, while those in the control group were externally applied with blank drugs plus conventional Western medicine standard. The therapeutic course for all was 14 days. Changes in rash degree, cutaneous pruritus, xerosis cutis, and nails were observed in both groups before and after treatment. Blood routines as well as liver and kidney function tests were performed in both groups before and after treatment. Follow-up visit was also conducted during progression-free survival (PFS). Results A total of 185 patients finished this clinical trial. Ten dropped out in the treatment group and 6 in the control group. The effective rates of rash degree, cutaneous pruritus, xerosis cutis, and nail changes were 90.1 % (109/121 ), 57.9% (70/121 ), 57. 9% (70/121 ), and 16. 5% (20/121) in the treatment group, respectively. They were 14. 1% (9/64), 6. 3% (4/64), 1. 6% (1164), and 0 (0/64) in the control group, respectively. Significant difference existed in all these indices between the two groups (X² = 105. 1022, 51. 3312, 59. 1777; P <0. 05). No serious drug-related adverse events occurred during clinical observation, with relatively better safety. The satisfaction was 95. 40% (125/131) in the treatment group and 57. 1 % (40/70) in the control group. No statistical difference in PFS was observed between the two groups (X² = 2. 006, P > 0. 05). Conclusions ZPL had significantly curative effect in treatment of EGFRIs-related skin adverse reactions, with no obvious adverse reactions. Howev- er, more randomized control trials are needed to verify these findings.

[Treatment of Epidermal Growth Factor Receptor Inhibitors Associated Adverse Skin Reactions by Zhiyang Pingfu Liquid: a Clinical Study].

OBJECTIVE: To study the curative effect of Zhiyang Pingfu Liquid (ZPL) in treating epidermal growth factor receptor inhibitors (EGFRIs) associated adverse reactions of the skin. METHODS: All 54 patients with pathologically confirmed malignant tumor had EGFRIs induced adverse reactions of the skin to various degrees. ZPL was externally applied for them all, once or twice per day, 14 days consisting of one therapeutic course. Changes of adverse skin reactions, time for symptoms relief, adverse skin reaction types suitable for ZPL were observed before and after treatment. RESULTS: EGFRIs associated skin adverse reactions were improved to various degrees after they used ZPL. The shortest symptoms relief time was 1 day while the longest was 12 days, with an average of 6.93 days and the median time 7 days. Compared with before treatment, itching, rash/scaling, acne/acneform eruptions were obviously improved (P < 0.05). CONCLUSION: ZPL could alleviate EGFRls associated adverse skin reactions, especially showed better effect on itching, rash/scaling, acne/acneform eruptions.

Clinical study of Jiawei Huangqi Guizhi Wuwu Decoction in preventing and treating peripheral neuro-sensory toxicity caused by oxaliplatin.

OBJECTIVE: To evaluate the efficacy of Jiawei Huangqi Guizhi Wuwu Decoction (JHGWD) in treating neuro-sensory toxicity induced by oxaliplatin. METHODS: A randomized controlled self-crossover trial was performed. Thirty-one patients were randomly divided into AB and BA groups. Patients in A cycle belonged to the treated group, who were treated with chemotherapy combined with oxaliplatin plus JHGWD. Patients in B cycle belonged to the control group and were treated with chemotherapy alone. The peripheral neuro-sensory toxicity was observed and analyzed. RESULTS: The main neurotoxicity was cold-induced paresthesia after the use of oxaliplatin, which included hyperaesthesia, chill, anaesthesia in the extremities, electrified sensation, formication, foreign body sensation and pain that might be exacerbated by exposure to cold. Twenty patients (64.5%) suffered from neuro-sensory toxicity in the treated group and 27 cases (87.1%) in the control group. Symptoms were more serious and lasted longer in the control group than those in the treated group (P < 0.01). CONCLUSION: JHGWD could prevent and reduce the occurrence and intensity of acute peripheral neuro-sensory toxicity caused by oxaliplatin.