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,result...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.展开更多
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)w...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.展开更多
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). M...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.展开更多
AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single a...AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years(range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve(AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were reevaluated and responses to therapy based on com-puter tomography(CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS(V19).RESULTS: A median of 10 cycles(range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.展开更多
Purpose:?The treatment of advanced breast cancer (ABC) is still challenging aiming mainly to improve or maintain the quality of life. The efficacy of pegylated liposomal doxorubicin (PLD) was proven in patients with A...Purpose:?The treatment of advanced breast cancer (ABC) is still challenging aiming mainly to improve or maintain the quality of life. The efficacy of pegylated liposomal doxorubicin (PLD) was proven in patients with ABC.?Because its expensive treatment?there is a great need to find the predictive factors for the clinical outcome of PLD.?Our purpose was to evaluate the factors which?would affect the clinical outcomes in patients receiving PLD for advanced breast cancer. Methods: Retrospectively, we studied the medical records of 60 eligible patients during the period of seven years (Jan.?2011-Dec.?2017).?All patients?were treated in Medical Oncology Department, South Egypt Cancer Institute, Assiut?University,?Egypt. We included only patients with visceral metastasis who received at least 2 cycles of PLD and had radiological assessment after that. Clinical benefit rate of PLD and survival outcome were assessed and correlated with patients and disease?characteristic. Results:?The majority of patients had a performance status grade II (81.7%), recurrent disease (86.7%), more than one metastatic site (83.3%), and chemoresistance to previous anthracycline (75%).?The clinical benefit rate (CBR) to PDL was 30%. We found statistical?significant association between higher CBR and biological subtypes (p??0.001), type of metastatic breast disease (p?=?0.003), chemosensitivity to anthracycline (p??0.001), and the number of previous lines of chemotherapy (p?=?0.041).?The median progression-free survival (PFS) was five months. There was a statistically-significant improvement of PFS among patients with anthracycline-sensitive tumors compared to those with anthracycline-resistant tumors (10 months vs. 5 months, respectively, p?=?0.004). The most common toxicity was palmar-plantar erythrodysesthesia (28% for all grade and 9% for grade 3 or more). There was no severe cardiotoxicity or treatment-related death.?Conclusion:?Pegylated liposomal doxorubicin appears to be more effective in patients?with (luminal B with Her2neu?positive, triple-negative and in her2neu amplified), also we noticed that de novo metastatic disease, patient who are not heavily pretreated tumors and patients with the anthracycline-sensitive tumor get more benefit from PLD than others.展开更多
<strong>Introduction:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The treatment of meta...<strong>Introduction:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The treatment of metastatic breast cancer (MBC) is still challenging.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Many studies documented the efficacy of</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">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. </span><b><span style="font-family:Verdana;">Aim of the work:</span></b></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">We conducted this trial to outline the cardiac safety of HCD of PLD in patients </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">with MBC who previously received conventional anthracyclines. </span><b><span style="font-family:Verdana;">Methods:</span></b> <span style="font-family:Verdana;">During the period of nine years (January 2011 to December 2019). We extracted</span><span style="font-family:Verdana;"> 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. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> 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/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> (± SD of 250.2) and a range of 100</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">1200 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;">. About thirty-one (38.3%) patients received high </span><span><span style="font-family:Verdana;">cumulative dose (400 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> or more), while the remaining 50 patients did not.</span></span></span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">The decline in </span><a name="_Hlk36276945"></a><span style="font-family:Verdana;">left ventricular ejection fraction (LVEF) was relatively rare;and</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 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</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">= </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">0</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">.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 </span><span style="font-family:Verdana;">patients </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">received HCD of PLD when compared to those </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">did not reach</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> the HCD (38.7% versus 16% respectively;p</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">=</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 0</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.021).</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Conclusion: </span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Our </span><span style="font-family:Verdana;">study concluded that the use of PLD seems to be a justified agent in the treatment</span><span style="font-family:Verdana;"> of MBC who previously treated by</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">conventional anthracyclines in the adjuvant, metastatic or both settings, even in patients reaching the cumulative dose of conventional anthracycline.</span></span></span>展开更多
OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal dox...OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal doxorubicin (PLD, Caelyx^(?)), vincristine,and reduced-dose dexamethasone combinationtherapy in newly diagnosed multiple myeloma (MM)patients in a Chinese population.METHODS This was an open-label, single-armstudy in which newly diagnosed patients with MMreceived PLD 40 mg/m^2 intravenously on Day 1,vincristine 1.4 mg/m^2 intravenously (maximum 2 mg)on Day 1, and 40 mg of dexarnethasone (intravenouslyor orally) from Day 1 to Day 4. Treatment wasrepeated every 28 days for at least 4 cycles.RESULTS In the intent-to-treat (ITT) analysis, theoverall response rate was 68.29%, and the completeremission rate was 10.98%. The incidence of alladverse events was 46.34%. The most commonnon-hematologic toxicities were palmar-plantarerythrodysesthesia (13.4%) and stomatitis (6.1%).CONCLUSION PLD, vincristine, and a reduceddosedexamethasone combination (DVd) is aneffective and safe regimen in newly diagnosed MMpatients in a Chinese population.展开更多
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 t...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.展开更多
OBJECTIVE Pegylated liposomal doxorubicin (PLD;CAELYX^(?)), a novel formulation of doxorubicin with enhancedtherapeutic efficacy and reduced toxicity, has demonstratedimproved progression-free survival in recurrent or...OBJECTIVE Pegylated liposomal doxorubicin (PLD;CAELYX^(?)), a novel formulation of doxorubicin with enhancedtherapeutic efficacy and reduced toxicity, has demonstratedimproved progression-free survival in recurrent or refractoryovarian cancer. The objective of this open-label, noncomparative,observational study was to determine the efficacyand safety of PLD monotherapy or combination therapy withcarboplatin for patients with recurrent or refractory ovariancancer.METHODS Sixty-two patients with recurrent or refractoryovarian cancer who completed a platinum-based chemotherapyregimen and demonstrated platinum sensitivity for first-linetreatment at least 6 months prior to study entry were enrolledin 20 centers in China. PLD was given as monotherapy (50mg/m^2 infused over 60 minutes) or as combination therapy(30 mg/m^2 1-hour infusion) with carboplatin (area under thecurve 5 mg.min/mL 1-hour infusion) on day 1 every 28 daysfor 4 cycles. The primary endpoint was objective response (OR)rate or CA-125 level. Secondary endpoints included time toresponse, time-to-progression, health-related quality of life, andsafety.RESULTS Overall, 48% of the 62 evaluable patients achieveda confirmed OR. More patients receiving PLD and carboplatinachieved an OR vs the PLD monotherapy group (63% vs. 37%).The median time to response and disease progression was58.5 days and 56.0 days, respectively. Overall and drug-relatedadverse 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 deathswere reported.CONCLUSION PLD is an effective and well tolerated agentin women with recurrent or refractory epithelial ovarian cancer.展开更多
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 c...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.展开更多
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: T...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: T<sub>1/2</sub> was (19.282 ± 10.305) h, C<sub>max</sub> was (118514.828 ± 26155.134) ng/mL, AUC<sub>0-24</sub> and AUC<sub>0-∞</sub> were (1216659.205 ± 192706.268) ng/mL⋅h and (2082244.523 ± 860139.487) ng/mL⋅h, MRT<sub>0-24</sub> and MRT<sub>0-∞</sub> 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.展开更多
文摘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.
文摘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.
文摘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.
文摘AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years(range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve(AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were reevaluated and responses to therapy based on com-puter tomography(CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS(V19).RESULTS: A median of 10 cycles(range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.
文摘Purpose:?The treatment of advanced breast cancer (ABC) is still challenging aiming mainly to improve or maintain the quality of life. The efficacy of pegylated liposomal doxorubicin (PLD) was proven in patients with ABC.?Because its expensive treatment?there is a great need to find the predictive factors for the clinical outcome of PLD.?Our purpose was to evaluate the factors which?would affect the clinical outcomes in patients receiving PLD for advanced breast cancer. Methods: Retrospectively, we studied the medical records of 60 eligible patients during the period of seven years (Jan.?2011-Dec.?2017).?All patients?were treated in Medical Oncology Department, South Egypt Cancer Institute, Assiut?University,?Egypt. We included only patients with visceral metastasis who received at least 2 cycles of PLD and had radiological assessment after that. Clinical benefit rate of PLD and survival outcome were assessed and correlated with patients and disease?characteristic. Results:?The majority of patients had a performance status grade II (81.7%), recurrent disease (86.7%), more than one metastatic site (83.3%), and chemoresistance to previous anthracycline (75%).?The clinical benefit rate (CBR) to PDL was 30%. We found statistical?significant association between higher CBR and biological subtypes (p??0.001), type of metastatic breast disease (p?=?0.003), chemosensitivity to anthracycline (p??0.001), and the number of previous lines of chemotherapy (p?=?0.041).?The median progression-free survival (PFS) was five months. There was a statistically-significant improvement of PFS among patients with anthracycline-sensitive tumors compared to those with anthracycline-resistant tumors (10 months vs. 5 months, respectively, p?=?0.004). The most common toxicity was palmar-plantar erythrodysesthesia (28% for all grade and 9% for grade 3 or more). There was no severe cardiotoxicity or treatment-related death.?Conclusion:?Pegylated liposomal doxorubicin appears to be more effective in patients?with (luminal B with Her2neu?positive, triple-negative and in her2neu amplified), also we noticed that de novo metastatic disease, patient who are not heavily pretreated tumors and patients with the anthracycline-sensitive tumor get more benefit from PLD than others.
文摘<strong>Introduction:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The treatment of metastatic breast cancer (MBC) is still challenging.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Many studies documented the efficacy of</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">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. </span><b><span style="font-family:Verdana;">Aim of the work:</span></b></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">We conducted this trial to outline the cardiac safety of HCD of PLD in patients </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">with MBC who previously received conventional anthracyclines. </span><b><span style="font-family:Verdana;">Methods:</span></b> <span style="font-family:Verdana;">During the period of nine years (January 2011 to December 2019). We extracted</span><span style="font-family:Verdana;"> 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. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> 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/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> (± SD of 250.2) and a range of 100</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">1200 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;">. About thirty-one (38.3%) patients received high </span><span><span style="font-family:Verdana;">cumulative dose (400 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> or more), while the remaining 50 patients did not.</span></span></span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">The decline in </span><a name="_Hlk36276945"></a><span style="font-family:Verdana;">left ventricular ejection fraction (LVEF) was relatively rare;and</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 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</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">= </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">0</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">.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 </span><span style="font-family:Verdana;">patients </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">received HCD of PLD when compared to those </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">did not reach</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> the HCD (38.7% versus 16% respectively;p</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">=</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 0</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.021).</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Conclusion: </span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Our </span><span style="font-family:Verdana;">study concluded that the use of PLD seems to be a justified agent in the treatment</span><span style="font-family:Verdana;"> of MBC who previously treated by</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">conventional anthracyclines in the adjuvant, metastatic or both settings, even in patients reaching the cumulative dose of conventional anthracycline.</span></span></span>
文摘OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal doxorubicin (PLD, Caelyx^(?)), vincristine,and reduced-dose dexamethasone combinationtherapy in newly diagnosed multiple myeloma (MM)patients in a Chinese population.METHODS This was an open-label, single-armstudy in which newly diagnosed patients with MMreceived PLD 40 mg/m^2 intravenously on Day 1,vincristine 1.4 mg/m^2 intravenously (maximum 2 mg)on Day 1, and 40 mg of dexarnethasone (intravenouslyor orally) from Day 1 to Day 4. Treatment wasrepeated every 28 days for at least 4 cycles.RESULTS In the intent-to-treat (ITT) analysis, theoverall response rate was 68.29%, and the completeremission rate was 10.98%. The incidence of alladverse events was 46.34%. The most commonnon-hematologic toxicities were palmar-plantarerythrodysesthesia (13.4%) and stomatitis (6.1%).CONCLUSION PLD, vincristine, and a reduceddosedexamethasone combination (DVd) is aneffective and safe regimen in newly diagnosed MMpatients in a Chinese population.
文摘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.
文摘OBJECTIVE Pegylated liposomal doxorubicin (PLD;CAELYX^(?)), a novel formulation of doxorubicin with enhancedtherapeutic efficacy and reduced toxicity, has demonstratedimproved progression-free survival in recurrent or refractoryovarian cancer. The objective of this open-label, noncomparative,observational study was to determine the efficacyand safety of PLD monotherapy or combination therapy withcarboplatin for patients with recurrent or refractory ovariancancer.METHODS Sixty-two patients with recurrent or refractoryovarian cancer who completed a platinum-based chemotherapyregimen and demonstrated platinum sensitivity for first-linetreatment at least 6 months prior to study entry were enrolledin 20 centers in China. PLD was given as monotherapy (50mg/m^2 infused over 60 minutes) or as combination therapy(30 mg/m^2 1-hour infusion) with carboplatin (area under thecurve 5 mg.min/mL 1-hour infusion) on day 1 every 28 daysfor 4 cycles. The primary endpoint was objective response (OR)rate or CA-125 level. Secondary endpoints included time toresponse, time-to-progression, health-related quality of life, andsafety.RESULTS Overall, 48% of the 62 evaluable patients achieveda confirmed OR. More patients receiving PLD and carboplatinachieved an OR vs the PLD monotherapy group (63% vs. 37%).The median time to response and disease progression was58.5 days and 56.0 days, respectively. Overall and drug-relatedadverse 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 deathswere reported.CONCLUSION PLD is an effective and well tolerated agentin women with recurrent or refractory epithelial ovarian cancer.
文摘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.
文摘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: T<sub>1/2</sub> was (19.282 ± 10.305) h, C<sub>max</sub> was (118514.828 ± 26155.134) ng/mL, AUC<sub>0-24</sub> and AUC<sub>0-∞</sub> were (1216659.205 ± 192706.268) ng/mL⋅h and (2082244.523 ± 860139.487) ng/mL⋅h, MRT<sub>0-24</sub> and MRT<sub>0-∞</sub> 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.