Clinical Study On Hand-foot Syndrome Caused By External Treatment Of Tumor Chemotherapy With Chinese Herbal Compound LC09

BACKGROUND AND OBJECTIVE:Hand-foot syndrome(HFS)is a type of clinical disease caused by chemotherapeutic agents characterized by erythema,edema,and skin pain in the limbs.The reviewl describes the advances in modem medicine related to HFS.HFS is commonly evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events.The risk of morbidity is related to the dose of chemotherapy,the schedule or mode of administration,and the number of medications.Current clinical trials suggest that HFS may be a good predictor of anti-cancer efficacy in capecitabine-treated breast and colorectal cancer patients.The pathological features of HFS are characterized by keratinocyte edema and necrosis,basal vacuolization,and perivascular lymphocyte infiltration.Its pathogenesis and chemotherapeutic drugs may be related to the toxic effects of exoskeletal adenocarcinoma of the hands and feet.For treatments,there is no suffient clinical evidence of treatment programs,but to interrupt chemotherapy with symptomatic treatment of pain,inflammation or prevention of infection.For prevention urea ointment is suggested.Review 2 is about the progress of HFS pathogenesis and herbal medicine in prevention or treatment from the view of traditional Chinese medicine.Through the clinical literature search of 147 Chinese herbal medicines intervened in HFS over the past 15 years,currently Chinese medicine practitioners believe that HFS belongs to the category of "Bi disease" and "collateral disease." The pathogenic factors include:drug toxicity,blood stasis,wet toxicity,blood heat,cold coagulation and so on.In the prevention and control program,it is divided into three methods:oral administration,external treatment,and intravenous injection.Traditional Chinese medicine orally represents prescriptions that use warming and replenishing blood as the main prescription,and drugs to remove heat and nourishing yin can be used based on clinical syndromes.External treatment of traditional Chinese medicine is mostly done by bubble washing method,smearing method,and external application method.The bubble washing method is commonly used clinically in the case of Buyang Huanwu Decoction.The applied ointnent/oil agent contains Yandi oil,Kangfuxin liquid,moist burn ointment,etc.The external application of medicinal powder Huangqiguizlliwuwu Decotion,Ruhuang powder and so on.At present,there are many herbal medicines for preventing and treating HFS,but there are few randomized,controlled,double-blind clinical trials and there is less high-level clinical evidence.This clinical study relies on the "National Science and Technology Support Program-Traditional Chinese Medicine Clinical Study of External Treatment of Compound Chinese Herbs LC09 on Hand-Foot Syndrome caused by Cancer Therapy "(Project code:2015BAI04B00,International Centre for Clinical Trials Registration Number:NCT02794493,Ethic Number:2016-6)to provide clinical evidence for the clinical efficacy,quality of life improvement,and safety of LC09 in the treatment of HFS.METHODS:A double-blind,randomized,placebo-controlled design was used.A total of 66 HFS patients meeting the enrollment criteria were selected,randomly divided into experimental group and control group.The patients were from outpatients or inpatients at China-Japan Friendship Hospital.The experimental group used Chinese medicine compound LC09 to wash the hands and feet,each time 2 bags soaked for 20 minutes,2 times a day until the end of 2 cycles of chemotherapy,the placebo intervention was used in the control group.Observed HFS grading and pain scores as main indicators before and after intervention,instrumental activity of daily living(IADL),dernatological quality of life index(DLQI),and chemotherapy completion rate as secondary indicators;blood routine,liver and kidney function before and after intervention Skin irritation and allergic reactions are evaluated for safety.Data management and statistical analysis using SPSS 17.0 software.The measurement data of each treatment group in each treatment group were statistically described by mean±standard deviation,compared with the baseline values during the screening period,and the paired t-test was used to compare the difference before and after treatment in the group.Changes in the two groups before and after treatment were compared using analysis of variance(ANOVA).The count data of each treatment group in different treatment groups were statistically described by frequency(composition ratio).Changes in the two groups before and after treatment were analyzed by Chi-square test or Wilcoxon rank sum test.All statistical tests were performed using two-sided tests.P<0.05 was considered statistically significant.The efficacy evaluation was performed using PPS analysis(per protocol set)and FAS analysis(full analysis set).The FAS set was the main analysis data set.RESULTS:The efficacy of HFS was better in group A than in group B(46.88%vs.16.13%,P=0.0088).For pain rating,group A overall efficiency was higher than group B(58.06%vs.22.58%,P=0.0044).For IADL scores,the decrease in total scores for visits in group A was statistically significant compared with group B(Z_Wil=2.2697,P=0.0232).The DLQI score was no difference between group A and group B.The complete rate of chemotherapy in group A was significantly higher than that in group B(68.75%vs.22.58%,P=0.0002).No adverse reactions were observed in the A and B groups during the test.After unblinding,group A was the experimental group and group B was the control group.CONCLUSION:LC09 granules have good effect on degrading and analgesic of capecitabine-induced HFS,which are safe and suitable for clinical promotion.In the future,it is necessary to increase the sample size and use a new kind of life-quality scale suited for HFS patients to further evaluate the effect of LC09 granules on the life quality improvement.