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.

First line anlotinib plus liposomal doxorubicin for locally advanced or metastatic soft tissue sarcoma:A prospective,single-arm trial

Objective:To examine the efficacy and safety of anlotinib as first-line therapy to treat locally advanced or metastatic soft-tissue sarcoma.Methods:This is a single-arm trial.Treatment-naïve patients(≥14 years)with locally advanced or metastatic soft tissue sarcoma were eligible.Each treatment cycle lasted for 3 weeks,and included liposomal doxorubicin(40-50 mg/m^(2))on day 1 and anlotinib(12 mg)on days 8-21.Starting from the 9th cycle,treatment consisted of only anlotinib.Treatment continued until disease progression or intolerable toxicities.The primary efficacy end point was progression-free survival(PFS).Results:Eight patients were enrolled between July 25,2019 and January 8,2020.The median number of treatment cycles was 5.5.Within 5.9 months median follow-up,PFS events occurred in 4(4/8,50%)patients.The median PFS was 11.3 months and the 6-month PFS rate was 56%.No patients attained complete response and 2 patients(fibrosarcoma,1 patient and undifferentiated pleomorphic sarcoma,1 patient)achieved partial response.Three patients(fibrosarcoma,2 patients and synovial sarcoma,1 patient)had stable disease.The objective response rate was 25%(2/8)for the study population,and the disease control rate was 75%(6/8).No new safety concerns emerged.Conclusions:Anlotinib plus liposomal doxorubicin demonstrated antitumor activities in previously untreated locally advanced or metastatic soft tissue sarcomas.Due to the small sample size,further investigations with a larger population should be undertaken to confirm the study findings.

Activity and safety of pegylated liposomal doxorubicin,5-fluorouracil and folinic acid in inoperable hepatocellular carcinoma:A phase Ⅱ study

AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase Ⅱ study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA). METHODS: Thirty-one patients with hystologically- confirmed, inoperable HCC, received combination chemotherapy with PLD 25 mg/mq on d 1, 5FU 1200 mg/mq in 48 h continuous infusion, and oral FA 30 mg on d 1 and 2 every 3 wk until disease progression or intolerable toxicity. RESULTS: The median age was 65 years (range 41-82) and 28 patients were hepatitis C virus seropositive (90%). The majority of patients were Child-Pugh Class B (55%). Two patients showed a partial response (PR), and 16 had stable disease (SD). With a median follow-up of 14 mo, the median time to progression of all evaluable patients was 4 mo (95% CI 1.7-7). Median overall survival was 9 mo (95% CI 3-24 mo). After 1 year, 9 of 18 PR/SD patients were alive. Chemotherapy was well tolerated. CONCLUSION: PLD/FU/FA combination seems capable of achieving durable stabilization of HCC. The manageable toxicity supports a role for combination with other anticancer agents.

Neoadjuvant Combination Chemotherapy with Pegylated Liposomal Doxorubicin and Vinorelbine for Locally Advanced Breast Cancer

OBJECTIVE In China, vinorelbine plus an anthracycline is a common neoadjuvant regimen for locally-advanced breast cancer （LABC）. Pegylated liposomal doxorubicin （PLD） is an alternate anthracycline formulation with a more favorable safety profile compared with conventional anthracyclines. METHODS In this open-label trial, 61 women with LABC received up to 6 cycles of PLD 30 mg/m2 on Day 1 and vinorelbine 25 mg/m2 on Days 1 and 8 every 21 days. Hormone receptor and/or HER2 status was not routinely available. RESULTS The overall clinical response rate （primary efficacy endpoint） was 80% （95% CI： 68%-89%）. Two patients achieved a pathological complete response （3%）, with 75% having their tumor down-staged, and 89% proceeding to tumor resection. The most frequent nonhematologic adverse events were stomatitis, fever, rash, and palmar-plantar erythrodysesthesia, with none considered serious. Grade 3 or 4 neutropenia and thrombocytopenia occurred in 10% and 2% of patients, respectively. CONCLUSION PLD plus vinorelbine demonstrated comparable efficacy to conventional anthracyclines plus vinorelbine in the neoadjuvant treatment of LABC, but may offer safety advantages.

Pegylated Liposomal Doxorubicin as a Single Agent or as Combination Therapy with Carboplatin in Patients with Recurrent or Refractory Epithelial Ovarian Cancer

OBJECTIVE Pegylated liposomal doxorubicin （PLD; CAELYX ）, a novel formulation of doxorubicin with enhanced therapeutic efficacy and reduced toxicity, has demonstrated improved progression-free survival in recurrent or refractory ovarian cancer. The objective of this open-label, noncomparative, observational study was to determine the efficacy and safety of PLD monotherapy or combination therapy with carboplatin for patients with cancer. recurrent or refractory ovarian METHODS Sixty-two patients with recurrent or refractory ovarian cancer who completed a platinum-based chemotherapy regimen and demonstrated platinum sensitivity for first-line treatment at least 6 months prior to study entry were enrolled in 20 centers in China. PLD was given as monotherapy （50 mg/m2 infused over 60 minutes） or as combination therapy （30 mg/m2 1-hour infusion） with carboplatin （area under the curve 5 mg.min/mL 1-hour infusion） on day 1 every 28 days for 4 cycles. The primary endpoint was objective response （OR） rate or CA-125 level. Secondary endpoints included time to response, time-to-progression, health-related quality of life, and safety. RESULTS Overall, 48% of the 62 evaluable patients achieved a confirmed OR. More patients receiving PLD and carboplatin achieved an OR vs the PLD monotherapy group （63% vs. 37%）. The median time to response and disease progression was 58.5 days and 56.0 days, respectively. Overall and drug-related adverse events were reported for 39% and 34%, respectively. The most commonly reported adverse events were stomatitis （22.6%） and palmar-plantar erythroderma （9.7%）. Two deaths were reported. CONCLUSION PLD is an effective and well tolerated agent in women with recurrent or refractory epithelial ovarian cancer.

Meta-Analysis of Trials Comparing Gemcitabine and Pegylated Liposomal Doxorubicin for Treatment in Women with Progressive or Recurrent Ovarian Cancer

OBJECTIVE To evaluate the efficacy and adverse effects ofgemcitabine versus pegylated liposomal doxorubicin in patientswith progressive or recurrent ovarian cancer.METHODS We conducted a systematic literature search toidentify all randomized controlled trials comparing gemcitabineand pegylated liposomal doxorubicin for progressive orrecurrent ovarian cancer. Trial data were reviewed and extractedindependently by 2 reviewers. We evaluated the quality of theincluded studies using the Handbook 5.0 recommend standardsand then analyzed data by Cochrane Collaboration's RevMan 5.0.RESULTS Two trials which included a total of 348 patients wereanalyzed. The results of meta-analysis showed that gemcitabineimproved disease control rates significantly better than pegylatedliposomal doxorubicin. A greater number of patients receivinggemcitabine experienced neutropenia compared with patientsreceiving pegylated liposomal doxorubicin; however, hand-footsyndrome and mucositis were more severe in patients receivingpegylated liposomal doxorubicin.CONCLUSION Gemcitabine provided a limited advantagecompared with pegylated liposomal doxorubicin. There existsan urgent need for more high-quality, multicenter, adequaterandomized, controlled clinical trials for comparing gemcitabinewith pegylated liposomal doxorubicin in patients withprogressive/recurrent ovarian cancer.

Resolution of pleural effusion in a IgD multiple myeloma after chemotherapy based on liposomal doxorubicin

IgD myelomas account for only 2% of all myelomas. This kind of hematological malignancy is severe and carries a bleak prognosis. Pleural effusion is very rare in multiple myeloma. We reported a case in which pleural effusion appeared at the end of the illness of IgD myeloma and treated with liposomal doxorubicin.

An Open-Label Study of Pegylated Liposomal Doxorubicin,Vincristine, and Reduced-Dose Dexamethasone Combination Therapy in Newly Diagnosed Multiple Myeloma Patients in the Chinese Population

OBJECTIVE Though doxorubicin is highly active in the treatment of multiple myeloma, its toxicity profile limits its therapeutic index. We performed this study to evaluate the efficacy and liposomal doxorubicin （PLD, Ca of pegylated , vincristine, and reduced-dose dexamethasone combination therapy in newly diagnosed multiple myeloma （MM） patients in a Chinese population. METHODS This was an open-label, single-arm study in which newly diagnosed patients with MM received PLD 40 mg/m2 intravenously on Day 1, vincristine 1.4 mg/m2 intravenously （maximum 2 rag） on Day 1, and 40 mg of dexamethasone （intravenously or orally） from Day 1 to Day 4. Treatment was repeated every 28 days for at least 4 cycles. RESULTS In the intent-to-treat （ITT） analysis, the overall response rate was 68.29%, and the complete remission rate was 10.98%. The incidence of all adverse events was 46.34%. The most common non-hematologic toxicities were palmar-plantar erythrodysesthesia （13.4%） and stomatitis （6.1%）. CONCLUSION PLD, vincristine, and a reduceddose dexamethasone combination （DVd） is an effective and safe regimen in newly diagnosed MM patients in a Chinese population.

Cardiac Safety with High Cumulative Dose of Pegylated Liposomal Doxorubicin in Patients with Metastatic Breast Cancer Previously Treated with Conventional Anthracyclines

Introduction: The treatment of metastatic breast cancer (MBC) is still challenging. Many studies documented the efficacy of pegylated liposomal doxorubicin (PLD) in patients with MBC, but there is a limited data about the cardiac safety with high cumulative dose (HCD) of PLD. Aim of the work: We conducted this trial to outline the cardiac safety of HCD of PLD in patients with MBC who previously received conventional anthracyclines. Methods: During the period of nine years (January 2011 to December 2019). We extracted the data of the patients with MBC receiving PLD at Medical Oncology Department, South Egypt Cancer Institute, Assiut University. These included patients’ demographics and therapeutic data including the full data of PLD, prior conventional anthracyclines, prior trastuzumab, and prior radiotherapy. Also, data about comorbidities as well as cardiac and other toxicities of PLD were obtained. The data was analysed using SPSS v. 21. Results: For all 81 eligible patients, the mean age was 43.9 years (±standard deviation (SD) 13.2). The mean cumulative dose of PLD was 378.4 mg/m2 (± SD of 250.2) and a range of 100 - 1200 mg/m2. About thirty-one (38.3%) patients received high cumulative dose (400 mg/m2 or more), while the remaining 50 patients did not. The decline in left ventricular ejection fraction (LVEF) was relatively rare;and of low grade. Grade 2 decline in LVEF occurred in only two patients who received high cumulative dose of PLD, and only one patient who did not reach HCD (p = 0.555). Grade 3 or 4 decline in LVEF did not occur in patients either with or without HCD. Regarding other toxicities, there was a significant increase in incidence of all grades palmar plantar erythrodysesthesia (PPE) in patients who received HCD of PLD when compared to those who did not reach the HCD (38.7% versus 16% respectively;p = 0.021). Conclusion: Our study concluded that the use of PLD seems to be a justified agent in the treatment of MBC who previously treated by conventional anthracyclines in the adjuvant, metastatic or both settings, even in patients reaching the cumulative dose of conventional anthracycline.

Use of liposomal doxorubicin for adjuvant chemotherapy of breast cancer in clinical practice

Breast cancer is one of the malignant tumors with the highest morbidity and mortality. It is helpful to reduce the rate of tumor recurrence and metastasis by treating breast cancer with adjuvant chemotherapy, so as to increase the cure rate or survival of patients. In recent years, liposomes have been regarded as a kind of new carrier for targeted drugs. Being effective for enhancing drug efficacy and reducing side effects, they have been widely used for devel- oping anticancer drugs. As a kind of anthracycline with high anticancer activity, doxorubicin can treat or alleviate a variety of malignant tumors effectively when it is used on its own or in combination with other anticancer drugs~ Alt- hough liposomal doxorubicin has been extensively used in the adjuvant chemotherapy of breast cancer, its exact therapeutic efficacy and side effects have not been definitely proven. Various clinical studies have adopted different combined regimes, dosages, and staging, so their findings differ to certain extent. This paper reviews the clinical application of liposomal doxorubicin in the adjuvant chemotherapy of breast cancer and illustrates therapeutic effects and side effects of pegylated liposomal doxorubicin （PLD） and non-PLD （NPLD） in clinical research, in order to discuss the strategies for applying these drugs in such adjuvant chemotherapy, looking forward to providing references for related research and clinical treatment in terms of dosage, staging, combined regimes, and analysis methods and so on.

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers

Aims:To determine the safety and efficacy of microwave ablation(MWA)and transarterial chemoembolization(TACE)with doxorubicin hydrochloride liposome(DHL)in patients with primary liver cancer(PLC)and metastatic liver cancer(MLC).Materials and methods:The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed.Treatment-related adverse events(AEs)were recorded.Local tumor response was evaluated according to the modified RECIST criteria.Local tumor progression-free survival(LTPFS)and overall survival(OS)were calculated using the Kaplan-Meier method.Results:Altogether,96 patients with liver cancer were included(PLC,n=45;MLC,n=51).Forty(41.7%)patients experienced AEs during treatment,and eight(8.3%)patients developed grade 3 AEs.Compared to before treatment,the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment.The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC.The median OS was not reached in patients with PLC or MLC.The 1-month and 3-month disease control rates reached more than 80%in both groups.Conclusion:MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.

Nonclinical Study of the Active Components of Doxorubicin Hydrochloride Liposome Injection in Vivo

Objectives: A non-clinical study was performed to establish a LC-MS/MS method to determine the in vivo active components of doxorubicin hydrochloride liposome injection in the plasma of Sprague-Dawley rats. Methods: Ten male SD rats were administered tail vein with a single dose of 10 mg/kg, and the concentrations of doxorubicin hydrochloride in plasma, heart, liver, spleen, lung, and kidney were determined by liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated. Results: The final concentration of doxorubicin hydrochloride ranged from 500 ng/mL to 250,000 ng/mL, and the lower limit of quantification was 500 ng/mL;the main pharmacokinetic parameters: T1/2 was (19.282 ± 10.305) h, Cmax was (118514.828 ± 26155.134) ng/mL, AUC0-24 and AUC0-∞ were (1216659.205 ± 192706.268) ng/mL⋅h and (2082244.523 ± 860139.487) ng/mL⋅h, MRT0-24 and MRT0-∞ were (9.237 ± 0.423) h and (26.52 ± 14.015) h, respectively, and clearance (CL) was (0.005 ± 0.002) mL/h⋅ng. Conclusions: The method is simple, rapid, and sensitive, which can be used for the determination of doxorubicin hydrochloride concentration in the plasma of SD rats and pharmacokinetic non-clinical studies.

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.

Conventional treatments and non-PEGylated liposome encapsulated doxorubicin for visceral leishmaniasis:A scoping review

Visceral leishmaniasis(VL),also known as Kala-azar,is caused by Leishmania(L.)donovani complex,which includes L.donovani and L.infantum and is associated with a high death rate as compared to the cutaneous and subcutaneous form.Treatment of VL includes chemotherapeutic agents which are associated with some major hurdles like toxicities,parenteral administration,high cost,parasite resistance and stability.Hence,there is an urgent requirement to develop novel chemotherapeutic agents or repurposing of existing drugs against VL.Developing formulation of new chemical entity for the treatment of VL is laborious,time consuming and associated with huge financial burden.However,screening of existing chemotherapeutic agents is a good alternative to avail cost-effective treatment option for VL.Non-PEGylated liposome encapsulated doxorubicin(Myocet®)is proposed as an alternative treatment option for VL in this review article.Here,we covered the fundamental aspects of VL,loophole associated with available current treatment strategies and non-PEGylated liposome encapsulated doxorubicin as a novel alternative formulation for treating VL,as this liposomal delivery system of doxorubicin might passively target the intra-cellular regions of macrophage.

Retrospective analysis of patients with rare-site and metastatic giant cell tumor

A giant cell tumor occurs mainly in the proximal tibia,humerus,distal radius bone and the pelvic bone.It is rarely observed in such sites as the ribs and the temporal bone.The condition is primarily treated with surgical excision and functional reconstruction.The effect of chemotherapy on lung metastases and locally advanced giant cell tumors has remained unknown.We collected and analyzed the data of six patients with rare giant cell tumors located in the head and neck patients.After an average follow-up of 42.6 months after surgery （14 to 90 months）,no local recurrence or metastasis was observed.We also collected and analyzed the data of five patients with metastatic giant cell tumors who were undergoing surgery for the primary tumor before; of three patients who had experienced multiple chemotherapy cycles,one had spontaneous regression,and one survived for long timer despite progression.The other two patients had their major metastatic lesions resected by surgery,and presented long-term survival during the follow up.In addition,this study reports one patient with locally advanced giant cell tumor of the rib,who has undergone successful surgical resection following two cycles of chemotherapy with ifosfamide and liposomal doxorubicin.Complete resection of the lesion at the head and neck is the key to relapse-free survival.The prognosis of lung metastases in patients with giant cell tumors is relatively satisfying.Neoadjuvant chemotherapy is also conducive to the surgery for locally advanced lesions and improvement of the quality of life.

A case of diffuse large B-cell lymphoma with interstitial pneumonia

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia(IP)during treatment.The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen,which included rituximab,cyclophosphamide,doxorubicin liposomes,vincristine,and prednisone(R-CDOP regimen).After 3 cycles,the treatment was assessed as effective.However,following the 4th cycle,the patient experience shortness of breath after physical activity.A repeat lung computer tomography indicated IP,which completely recovered after receiving“full coverage”treatment.Subsequently,the patient underwent 2 cycles of cyclophosphamide,doxorubicin liposomes,vincristine,and prednisone(CDOP),followed by local radiotherapy.Currently,the patient is now being followed up with regular reviews.