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.

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.

Pegylated liposomal doxorubicin/carboplatin combination in ovarian cancer, progressing on single-agent pegylated liposomal doxorubicin

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.

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.

Predictive and Prognostic Factors for the Outcome of the Patients Receiving Pegylated Liposomal Doxorubicin for Advanced Breast Cancer

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.

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.

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.

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.

手足低温法预防盐酸多柔比星脂质体致手足综合征的效果

目的 从临床角度探究局部冷敷法在盐酸多柔比星脂质体(PLD)致相关手足综合征(HFS)中的应用效果。方法 采取非同期随机对照试验,选取2021年6月至2023年6月河北工程大学附属医院乳腺外科已治疗的乳腺癌患者为研究对象,以2021年6月至2022年5月化疗的乳腺癌患者为常规护理组(n=58),2022年6月至2023年6月化疗的乳腺癌患者为局部冷敷法组(n=55)。比较两组在4次PLD化疗阶段HFS的发生率、患者治疗依从性、诊疗满意度及患者就医体验感。结果 局部冷敷法组HFS发生率为23.6%(13/55),常规护理组为44.8%(26/58);局部冷敷法组HFS发生率低于常规护理组(χ^(2)=5.609,P=0.018)。局部冷敷法组HFS严重程度轻于对照组(P<0.05)。局部冷敷法组Ⅱ级及以上HFS发生率为10.9%、常规护理组为25.9%;局部冷敷法组Ⅱ级及以上HFS发生率低于常规护理组(P<0.05)。局部冷敷法组治疗依从性及满意度均高于常规护理组(P<0.05)。结论 局部冷敷法可有效预防和降低PLD化疗过程中HFS的发生率和严重程度、提高患者护理干预的依从性、患者满意度较高。

TanshinoneⅡA improves distribution and anti-tumor efficacy of pegylated liposomal doxorubicin via normalizing the structure and function of tumor vasculature in hepa1-6 hepatoma mice model

OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatoma mice model.METHODS: Hepa1-6 hepatoma-bearing mice were treated with TanⅡA for 14 d. Distribution and anti-tumor efficacy of PLD, and the structure and function of the tumor vasculature were evaluated using various techniques.RESULTS: TanⅡ A significantly reduced the micro-vessel density(MVD). After Tan vascular walls were betteⅡr s A treatment,the tumor tructured, as the increased coverage of the pericytes and the promoted contact of the basement membrane and endothelial cell. Functional tests showed that tumor hypoxia was improved and the exudation amount of Evans blue in the parenchyma of the tumor decreased. In addition, mice treated with TanA had greater PLD penetration distance intratumoⅡrally. Furthermore, combined therapy of Tanibited tumor growth.ⅡA and PLD significantly inhCONCLUSION: This study suggests that Tanasculature andⅡ h A helps normalizing the tumor vas therapeutic potential in increasing the distribution of chemotherapy drug in the tumor.

含PLD的CHOP方案用于高龄晚期DLBCL一线化疗的疗效及安全性

目的:探讨含聚乙二醇多柔比星脂质体(PLD)的CHOP方案用于高龄晚期弥漫大B淋巴瘤(DLBCL)的临床疗效及安全性。方法:选取2010年2月至2014年2月于本院接受治疗的DLBCL患者50例,按照治疗方式分为2组,各25例,25例接受标准CHOP治疗方案治疗(标准CHOP组),另25例患者接受含PLD的CHOP治疗方案治疗(PLD+CHOP组),其中PLD的剂量为30 mg/m2,其余药物的剂量采取标准CHOP方案中规定的剂量。随访患者18个月,对比分析两组患者的治疗总有效率,生存率和不良反应发生率。结果:两组患者经过不同方案的治疗后,观察组患者6、12和18个月的生存率分别为88.0%、80.0%和76.0%,其中18个月的生存率明显高于对照组(P<0.05);观察组的治疗总有效率为80.0%,明显高于对照组的48.0%(P<0.05);观察组患者一般毒性反应如非血液学毒性、周围感觉神经病变和肺部感染、胃肠道反应和肝脏毒性的发生率与对照组相比无明显差异(P>0.05),而观察组患者的心脏毒性反应,如急性心肌梗死、充血性心力衰竭、房室传导阻滞和阵发性房性心动过速的发生率与对照组相比均明显降低。结论:含PLD的CHOP治疗方案(观察组)在治疗高龄晚期DLBCL患者的疗效确切,心脏毒性低,安全性较好,在临床治疗DLBCL的过程中值得推广应用。

基于深度学习的乳腺癌术后脂质体多柔比星与表柔比星个性化治疗推荐研究

目的比较机器学习(machine learning,ML)与因果领域个体化干预效果(individualized treatment effect,ITE)评估深度学习这两类方法在真实临床数据集上的个性化推荐性能差异,构建乳腺癌术后聚乙二醇脂质体多柔比星(pegylated liposomal doxorubicin,PLD)与表柔比星(epirubicin,EPI)的个体化药物治疗推荐模型,通过评估药物疗效来指导临床治疗方案。方法回顾性收集浙江大学医学院附属邵逸夫医院收治的904名乳腺癌患者临床资料,其中387例采用PLD治疗,517例采用EPI治疗,通过倾向性评分匹配法比较两组患者5年无病生存期(disease free survival,DFS)结局;应用CFR_WASS等6种ITE模型预测患者在两种药物治疗下5年DFS概率,使用随机森林等6种机器学习模型作为基准进行性能分析比较;根据受试者工作特征曲线下的面积(area under the receiver operating characteristic curve,AUROC)评估预测性能,通过计算实际使用治疗与模型推荐治疗一致组和对照组的5年DFS率差异评估治疗推荐有效性。结果153对匹配病例中,PLD组和EPI组5年DFS结局比较差异无统计学意义,16对病例PLD组临床结局优于EPI组,12对病例EPI组临床结局优于PLD组,验证两种药物存在个体治疗收益差异。CFR_WASS模型获得了最优预测性能(AUROC为0.7368);多数ML组与对照组的5年DFS率无明显差异,ITE组5年DFS率均低于对照组,差异有统计学意义(P<0.01),其中CFR_WASS组5年DFS率较对照组低2.13%。结论相比于ML模型,ITE评估深度学习模型能更准确地估计两种药物的个体化治疗效果,给出有效的个体化治疗推荐,具有一定临床应用价值。

清营汤防治乳腺癌PLD化疗后皮肤黏膜毒性反应临床观察

目的:观察清营汤在防治乳腺癌患者接受聚乙二醇化盐酸多柔比星脂质体化疗后皮肤黏膜毒性反应(MT)并发症的临床疗效。方法:选取符合纳入标准的乳腺癌患者60例,随机分为两组各30例。对照组不加用干预处理,治疗组加用清营汤口服,连续用药6周。分别记录两组患者治疗后MT及各症状(手足红肿综合征、皮疹、口腔炎)发生率、严重程度及安全性指标。结果:治疗组MT及各症状发生率及严重程度明显低于对照组,差异均有统计学意义(P﹤0.05),且安全性指标无明显差异。结论:乳腺癌患者配合清营汤可减轻MT及各症状发生率及严重程度,疗效较好。

初治弥漫大B细胞淋巴瘤患者利妥昔单抗相关间质性肺炎的临床分析:一项单中心的回顾性研究

目的探究初治弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者中利妥昔单抗相关间质性肺炎(rituximab-induced interstitial lung disease,RILD)的发生率及其与临床病理特征的相关性。方法回顾性收集2020年1月至2022年12月于首都医科大学附属北京同仁医院血液内科诊治的110例DLBCL患者的临床病理资料,所有患者均接受含利妥昔单抗的一线治疗方案,具体方案根据患者自身差异进行调整,每21 d为1个周期。在化疗第2、4个周期后及利妥昔单抗第8个周期治疗结束后分别通过胸部CT或PET-CT检查评估RILD的发生情况。通过卡方检验及多因素Logistic回归分析RILD的危险因素并拟合风险预测模型,构建列线图模型对RILD发生率进行预测。结果110例DLBCL患者经治疗后终末完全缓解率达84.2%。21例(19.1%)患者在治疗期间发生RILD,中位发生时间为一线治疗的第4个周期(范围:2~8个周期);治疗RILD的中位持续时间为10 d(范围:5~60 d);除5例无明显症状或轻症的患者未予药物治疗外,16例中重症患者均接受含糖皮质激素的治疗方案,所有患者经治疗后均好转。初治接受含多柔比星脂质体方案的患者RILD的发生率显著高于应用吡柔比星方案化疗的患者(29.7%vs 13.7%,P=0.043);吸烟(25.9%vs 16.9%,P=0.298)、年龄≥60岁(23.2%vs12.2%,P=0.156)的患者也有较高的RILD发生率,但差异均无统计学意义。根据上述危险因素拟合RILD风险预测模型,将患者分为高风险组与低风险组,结果两组间RILD的发生率差异有统计学意义(P=0.027);列线图模型分析结果显示,有吸烟史的年龄≥60岁且使用多柔比星脂质体的患者,RILD的发生率在35%以上。结论DLBCL患者在应用含利妥昔单抗方案化疗后应警惕RILD的发生,尤其是吸烟和高龄患者,在应用多柔比星脂质体后更应该加强对RILD的预防和监测。

含聚乙二醇脂质体多柔比星的CHOP样方案治疗初治老年晚期弥漫大B细胞淋巴瘤的Ⅱ期临床研究

目的：评价含聚乙二醇脂质体多柔比星（PLD）的CHOP样方案治疗初治老年晚期弥漫大B淋巴瘤（DLBCL）的疗效和安全性。方法：2011年11月至2014年3月共入组30例患者,中位年龄70（63~80）岁,24例（80.0%）国际预后指数≥3分;21例联合应用利妥昔单抗。进行前瞻性II期临床研究,以含PLD的CHOP样方案治疗初治老年晚期DLBCL。PLD剂量为30 mg/m2,环磷酰胺、长春新碱和强的松采用标准CHOP方案中的剂量。CD20阳性的患者可联合利妥昔单抗,计划完成6个周期。结果：客观缓解率为86.7%,其中完全缓解率为66.7%。中位随访20.1（0.7~38.5）个月,18个月总生存率及无进展生存率分别为82.4%及70.1%。主要不良反应为中性粒细胞减少。24例（80.0%）发生3~4级中性粒细胞减少。研究中患者左室射血分数及血清肌钙蛋白T无显著变化。4例（13.3%）在PLD输注后新发无症状性心电图异常。结论：含PLD的CHOP样方案是治疗初治老年晚期DLBCL患者毒性可接受的备选方案,缓解率较高,心脏安全性较好。

PEG化脂质体多柔比星在动物体内的药动学及组织分布

比较研究了PEG化脂质体多柔比星(阿霉素)受试制剂与进口同类参比制剂静注后,在动物体内的药动学及组织分布。采用HPLC法测定Beagle犬的血药浓度和荷瘤(Walker256)Wistar大鼠各组织药物浓度。结果显示,Beagle犬静注1mg/kg受试制剂及参比制剂后,药动学参数分别为t1/2β23.0和23.5h,表观分布容积0.060和0.062L/kg,AUC0-∞500.29和531.57μg·ml-1·h,多柔比星在犬体内的药代动力学过程均符合二室模型的特征。荷瘤(Walker256)Wistar大鼠静注5mg/kg受试制剂及参比制剂后,脾中含量最高,其次为肿瘤、小肠、肝,皮肤中含量最低。统计学分析显示,两制剂在犬体内主要药动学参数及大鼠组织肝、心、脾、肾、小肠、皮肤和肿瘤内的分布,无显著性差异(P>0.05)。

脂质体多柔比星联合卡铂治疗卵巢癌疗效及安全性的系统评价

目的：系统评价脂质体多柔比星联合卡铂治疗卵巢癌的疗效及安全性。方法：计算机检索Cochrane Library、Pubmed、EMbase、Web of Science、中国CNKI学术总库、万方数据库、维普中文科技期刊数据库和中国生物医学文献数据库，检索时间从建库截至2013年3月，同时追索纳入文献的参考文献，查找脂质体多柔比星联合卡铂及紫杉醇联合卡铂治疗卵巢癌的随机对照试验（RCT）。由2位研究者按照纳入、排除标准筛选文献，提取资料并依据CochraneHand—book5．0．1质量评价标准评价纳入文献后，采用RevMan5．1软件进行Meta分析。结果：纳入3个临床RCT，共1985例患者。Meta分析结果显示：总生存率两组差异无统计学意义（OR=0．85，95％C10．71～1．02，P=0．090），与紫杉醇联合卡铂相比，脂质体多柔比星联合卡铂治疗改善患者的中位无进展生存率（OR=1．15，95％CI1．03～1．30，P=0．020）效果更好，过敏反应（OR=0．28，95％C10．19—0．41，P=0．000）、脱发（0R=0．08，95％C10．06～0．10，P=0．000）、中性白细胞减少（OR=0．70，95％C10．58—0．84，P=0．000）和神经毒性（OR=0．17，95％C10．14～0．21，P=0．000）发生较少，但用药期间掌跖红斑（OR=3．82，95％CI2．85～5．13，P=0．000）和血小板减少症（OR=4．31，95％CI3．00～6．17，P=0．000）的发生却明显增加。结论：脂质体多柔比星联合卡铂与紫杉醇联合卡铂治疗卵巢癌的总体生存率相当，而中位无进展生存情况脂质体多柔比星联合卡铂有明显优势，且部分毒副反应明显减轻。

多柔比星脂质体联合卡铂治疗晚期或复发转移子宫内膜癌疗效分析

目的评价多柔比星脂质体联合卡铂治疗晚期或复发转移子宫内膜癌的临床疗效及安全性。方法 21例晚期或复发转移子宫内膜癌患者,给予多柔比星脂质体[30 mg·(m^2)^(-1)]+卡铂(AUC=5)联合化疗,每3周为1个周期,共6个周期,评价化疗有效率、无进展生存时间及不良反应。结果 21例患者中,完全缓解患者2例,部分缓解患者10例,有效率(ORR)为57.1%,无进展生存时间(PFS)中位时间为9.2个月。主要不良反应为血液毒性及胃肠道反应。仅1例患者出现Ⅳ度白细胞减少,Ⅲ度白细胞减少、血红蛋白减少、血小板减少分别为3,1,1例,17例患者出现胃肠道反应,其中Ⅰ度12例,Ⅱ度5例,3例出现口腔黏膜炎,1例发生手足综合征,8例出现脱发,1例发生肝脏毒性,未观察到肾脏毒性和心脏毒性反应。结论多柔比星脂质体联合卡铂治疗晚期或复发转移子宫内膜癌有效率较高,不良反应轻,可作为这类患者的挽救化疗方案。