Utility of cooling patches to prevent hand-foot syndrome caused by pegylated liposomal doxorubicin in breast cancer patients

BACKGROUND Pegylated liposomal doxorubicin(PLD)uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands,producing toxic free radicals and oxidative damage,resulting in hand-foot syndrome(HFS).Regional cooling can induce vasoconstriction to reduce the release of drugs in the limbs and reduce the accumulation of drugs in sweat glands;thus,decreasing the incidence and severity of HFS.AIM To study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term.METHODS This is a retrospective cohort study.Female breast cancer patients(n=101)who were treated with PLD in two breast wards at our department from February 2020 to February 2021 were enrolled in the study and were randomly divided into the cooling group(51 patients)and the control group(50 patients).Patients in the control group only received routine care,while the patients in the cooling group applied cooling patches,based on routine care,to the palm and back of the hands 15 min before chemotherapy infusion for 10 h.All patients took a corresponding dose of dexamethasone orally one day before chemotherapy,on the day of chemotherapy,and one day after chemotherapy.SPSS23.0 version was used to analyze the data in this study.The occurrence and severity of HFS was analyzed by the Mann-Whitney U test,and scores were analyzed by the Student’s t test or Wilcoxon rank-sum test.A P value<0.05 was regarded as statistically significant.RESULTS In this study,neither group of patients developed Grade 3 HFS.In the control group,the incidence of Grade 1 HFS and Grade 2 HFS was 38%and 2%,respectively.However,in the cooling group,only one person developed Grade 1 HFS(2%),and none of the patients developed Grade 2 HFS.These findings showed that cooling patches can effectively reduce the frequency and severity of HFS(P<0.0001)in the short-term.Before the fourth chemotherapy cycle,although general self-efficacy scale scores in the cooling group were low,they were still significantly higher than those in the control group(17.22±5.16 vs 19.63±6.42,P=0.041).Compared with the control group,the mean Hand-Foot Skin Reaction and Quality of Life Questionnaire score in the cooling group was significantly lower(18.08±7.01 vs 14.20±7.39,P=0.008).CONCLUSION Cooling patches can effectively reduce the frequency and severity of HFS caused by PLD in the short-term.In addition,it may help delay the decline in patients’self-efficacy.

Pazopanib Induced Hand-Foot Syndrome in a Patient Previously Treated with Sunitinib: A Possible Cumulative Skin Toxicity?

Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, is a skin toxicity that could be observed during target therapies such as with tyrosine-kinase inhibitors (TKI). It usually develops within the first 2 - 4 weeks of drug administration. We present a case of HFS induced by Pazopanib after 2 months of treatment, in patients previously treated with Sunitinib, suggesting a possible cumulative toxicity of two drugs. The clinical and therapeutic management of skin adverse reactions during TKI therapy usually requires 25% dose reduction and adequate local treatment. It is important for the clinicians to recognize clinical signs and symptoms of such skin toxicities. Attention should be paid especially when two or more drugs from the same class are used in combined treatment.

Stevens-Johnson syndrome and concurrent hand foot syndrome during treatment with capecitabine:A case report

BACKGROUND Capecitabine is used in combination with lapatinib as palliative treatment for human epidermal growth factor receptor 2-positive metastatic breast cancer.The most frequently reported adverse events attributed to capecitabine include diarrhea,hyperbilirubinemia,and hand-foot syndrome(HFS).A number of cutaneous adverse events have been attributed to capecitabine,including Stevens-Johnson syndrome(SJS)as a rare and potentially life-threatening mucocutaneous condition.We report the first case involving concurrent SJS and HFS after capecitabine and lapatinib treatment.CASE SUMMARY A 70-year-old woman with a history of breast cancer treatment visited our hospital for evaluation of painful skin lesions.Six weeks earlier,she had been prescribed capecitabine plus lapatinib as treatment for metastatic breast cancer.She subsequently developed worsening erythema and bullae on her palms and soles,as well as reddish macules on her back and chest wall.Histopathological evaluation of the chest wall lesions revealed extensive eosinophilic epidermal necrosis and separation of the epidermis from the dermis.The capecitabine plus lapatinib treatment was discontinued immediately and treatment was started using systemic steroids.This treatment resolved most lesions,although the lesions on her palms and soles required Vaseline gauze dressings,which resulted in reepithelialization.Therefore,we determined that the patient had concurrent SJS and HFS.Although the dermatological problems resolved,the patient ultimately died because of multiple organ failure.CONCLUSION Oral capecitabine treatment carries a risk of both HFS and also life-threatening adverse cutaneous drug reactions,such as SJS.

Relationship between Self-Care and Hand Foot Syndrome Specific Quality of Life in Cancer Patients

Purpose: The purpose of this study was to describe adherence to self-care for hand-foot syndrome (HFS) and the relationship between self-care and health-related quality of life (QOL). Methods: A cross-sectional study was conducted on 105 consecutive outpatients with HFS. To assess self-care for HFS and QOL, the participants were asked to complete self-care and HFS-14 (hand-foot syndrome specific QOL) questionnaires, respectively. Multiple regression models were used to identify the relationship between self-care and QOL. Results: Adherence to self-care for HFS was low, less than 50% for most of the items. Multivariate analysis revealed that poorer self-care (βs = -0.19;P = 0.03), depressive symptoms (βs = 0.43;P βs = 0.20;P = 0.04) were independent predictors of poorer QOL scores. Conclusions: We have identified a need for further research to develop effective programs of self-care in HFS.

Evaluation of the Preventive Effect of Regional Cooling Nursing on Hand Foot Syndrome Caused by Doxorubicin Hydrochloride Liposome

Purpose: To explore the preventive effect of Regional cooling comprehensive nursing on hand foot syndrome caused by pegylated liposomal doxorubicin (PLD). Method: Adopt overall sampling method. Patients who used the same adjuvant drugs from January to December 2020 were randomly divided into an intervention group and a control group. The patients in the two groups received routine nursing guidance and drug prevention for the use of amygdalin. The patients in the intervention group were required to take protective measures of Regional cooling during chemotherapy. The occurrence of hand foot syndrome during adriamycin liposome administration was compared between the two groups. Results: By comparing the adverse reactions of cases during Adriamycin Administration, the incidence rates of grade I, II and III hand foot syndrome in the control group were 28.8%, 7.6% and 27.5% respectively, and the incidence rates of grade I, II and III hand foot syndrome in the intervention group were 42.1%, 12.3% and 7.0% respectively, with statistical significance (P Conclusion: Regional cooling nursing and preventive behavior guidance can effectively reduce the severity of hand foot syndrome caused by adriamycin.

Observation of Curative Effect of Surgical Nursing in Patients with Grade III Hand-Foot Syndrome

Objective: To investigate the effect of surgical nursing on grade III Hand-Foot Syndrome (HFS) induced by Doxorubicin hydrochloride liposome chemotherapy after breast cancer surgery. Method: From January 2019 to December 2019, 10 patients with HFS grade III caused by Doxorubicin hydrochloride liposome chemotherapy after breast cancer surgery in the Breast Department of Cancer Prevention and Treatment Center of Sun Yat-sen University were selected, and surgical nursing methods were used to intervene and observe the therapeutic effects of the patients. Results: One patient was cured within 7 days, the cure rate was 10% in 7 days, 8 patients were cured within 10 days, the cure rate was 80% in 10 days, 10 patients were cured within 15 days, the cure rate was 100% in 15 days. Conclusion: The surgical nursing method is effective for patients with grade III HFS caused by Doxorubicin hydrochloride liposome chemotherapy after breast cancer surgery, shortening the treatment time of HFS, and is worthy of clinical promotion.

DNA damage-mediated cellular senescence promotes hand-foot syndrome that can be relieved by thymidine prodrug

Hand-foot syndrome(HFS)is a widely recognized dose-limiting cutaneous toxicity effect of fluoropyrimidine chemotherapy agents that impairs clinical benefits and treatment outcomes.Even though the cause and pathophysiology of HFS are relatively widely reported,how the toxicity of fluoropyrimidine translates into persistent inflammation has not been studied.Additionally,prevention and treatment strategies for HFS based on its mechanistic occurrence and development are scarce.In our study,we demonstrated that cGAS-STING signaling pathway-mediated cellular senescence played a critical role in the inflammatory reaction and provided a therapeutic solution for HFS.Mechanistically,DNA damage,as the primary cytotoxic cause,in keratinocytes induces cell cycle arrest,activates the cGAS-STING signaling pathway,and subsequently mediates cellular senescence,ultimately fueling a robust secondary inflammatory response that results in HFS.More importantly,the thymidine prodrug thymidine diacetate was proven to be effective in preventing HFS by compensating for thymidylate deficiency to facilitate the replication and repair of DNA and thus causing the escape from cellular senescence.These data highlight the importance of DNA damage-mediated cellular senescence in the etiology of HFS and provide a potential therapeutic anchor point for fluoropyrimidine-induced HFS.

Polymorphisms of MTHFR and TYMS predict capecitabine-induced hand-foot syndrome in patients with metastatic breast cancer

Background:Breast cancer is a global problem,and a large number of new cases are diagnosed every year.Capecit-abine is effective in patients with metastatic breast cancer(MBC).Hand-foot syndrome(HFS)is a common adverse effect of capecitabine.In this study,we investigated the association between single nucleotide polymorphisms(SNPs)in genes involved in capecitabine metabolism pathways and capecitabine-induced HFS in Chinese patients with MBC to identify some predictive genetic biomarkers.Methods:We selected 3 genes involved in capecitabine metabolism and screened genetic variants in these target genes.We genotyped a total of 22 SNPs in the thymidylate synthase gene(TYMS),the methylene tetrahydrofolate reductase gene(MTHFR),and the ribonucleotide reductase M1 gene(RRM1)in 342 MBC patients treated with capecit-abine-based chemotherapy.The genotype distributions of each SNP in patients with and without HFS were assessed using Pearson’sχ^(2)test,and the relationship between HFS and genotypes of SNPs was determined using logistic regression analysis.The association between SNPs and their corresponding gene expression was analyzed using the Blood expression quantitative trait loci(eQTL)browser online tools.Results:We found 4 positive sites for HFS in the TYMS and MTHFR genes:TYMS rs2606241(P=0.022),TYMS rs2853741(P=0.019),MTHFR rs3737964(P=0.029),and MTHFR rs4846048(P=0.030).Logistic regression analyses showed that the genotype AG of MTHFR rs3737964[odds ratio(OR)=0.54,95%confidence interval(CI)0.31-0.97,P=0.038]and MTHFR rs4846048(OR=0.54,95%CI 0.30-0.98,P=0.042)were protective factors of HFS,whereas the genotype CT of TYMS rs2853741(OR=2.25,95%CI 1.31-3.87,P=0.012)increased the risk of HFS.The association between the genotype GT of TYMS rs2606241(OR=1.27,95%CI 0.73-2.23,P=0.012)and HFS was uncertain.Further eQTL analyses confirmed that the alleles of rs3737964 and rs4846048 affected the gene expression levels of MTHFR in cis.Conclusions:We have identified four potentially useful pharmacogenetic markers,TYMS rs2606241,TYMS rs2853741,MTHFR rs3737964,and MTHFR rs4846048 to predict capecitabine-induced HFS in MBC patients.

Indicators of sorafenib efficacy in patients with advanced hepatocellular carcinoma

AIM:To determine significant indicators for the efficacy of sorafenib in patients with advanced hepatocellular carcinoma(HCC).METHODS:A total of 46 patients with Barcelona Clinic Liver Cancer stage C who received sorafenib for more than 30 d at the Iizuka Hospital from June 2009 to December 2012 were enrolled in this study.Multivariate and univariate analyses were performed to evaluate the associations of hepatic function according to Child-Pugh grade,location and size of the largest tumor and adverse events of sorafenib treatment,such as hand-foot syndrome(HFS),hypertension,diarrhea,and alopecia,with the efficacy of treatment,as measured by overall survival(OS)and time to progression(TTP).RESULTS:Patients included 39 men and 7 women whose ages ranged from 48 to 85 years(70.6±9.6years).HCC was classified according to etiology as follows:hepatitis C virus(n=26),hepatitis B virus(n=9),and other(n=11).Liver function in patients was categorized as Child-Pugh grade A(n=30)or B(n=16).Tumors were categorized by size[<5 cm(n=33)or>5 cm(n=13)]and the location of the largest tumor was used to categorize patients with intrahepatic(n=28)or extrahepatic(n=18)HCC.HFS,hypertension,diarrhea,and alopecia were present in22(47.8%),19(41.3%),15(32.6%)and 7 patients(15.2%),respectively.The median OS of all patients was 373 d and the median TTP was 112 d.The etiology of HCC did not correlate with the median OS and TPP.The median OS of patients with tumors<5 cm was significantly longer than those with larger tumors(496 vs 245 d;HR=0.19,95%CI:0.07-0.48;P<0.01).According to the results of a multivariate analysis,the size of the largest tumor affected OS(HR=0.22,95%CI:0.08-0.59;P<0.01).The median TTP was significantly longer in patients with extrahepatic compared to intrahepatic major HCC(224 vs 98 d;HR=0.32;95%CI:0.14-0.67;P<0.01).The median TTP of patients with HFS was significantly longer than those without it(195 d vs 83 d;HR=0.41,95%CI:0.20-0.82;P<0.05),and the median TTP was significantly longer in patients with hypertension(195 d vs84 d;HR=0.43,95%CI:0.21-0.84;P<0.05).According to the results of the multivariate analysis,extrahepatic major HCC(HR=0.36,P<0.01)and HFS(HR=0.44,P<0.05)prolonged TTP.CONCLUSION:Extrahepatic major HCC and HFS are associated with prolonged TTP and are useful indicators for judging the efficacy of sorafenib treatment.