Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer

Objective： To observe the efficacy and safety of albumin-bound paclitaxel （ABP） monotherapy in treating recurrent advanced non-small-cell lung cancer （NSCLC）. Methods： We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results： Of these 21 patients, the best overall response was partial response （PR） in 6 patients （28.6%）, stable disease （SD） in I0 patients （47.6%）, and progressive disease （PD） in 5 patients （23.8%）. The overall response rate （ORR） was 28.6% and the disease control rate （DCR） （PR ＋ SD） was 76.2%. The median progression-flee survival （PFS） was 4.0 months （95% CI, 5.0-7.0 months）. The main grade 3/4 toxicities included neutropenia （11.1%）, peripheral nerve toxicity （5.6%）, muscle and joint aches （5.6%）, and fatigue （5.6%）. Conclusions： The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.

Albumin-bound paclitaxel as new treatment for metastatic cholangiocarcinoma: A case report

BACKGROUND Cholangiocarcinomas are rare and very aggressive tumors.Most patients have advanced-stage or unresectable disease at presentation,and the systemic therapies have limited efficacy.Albumin-bound paclitaxel(nab-paclitaxel)is a solvent-free taxane that has been approved for the treatment of some cancers such as breast,non-small cell lung and pancreatic cancer,however it has not been applied to treat cholangiocarcinoma.We have both preclinical and clinical evidence of the efficacy of nab-paclitaxel in cholangiocarcinoma,yet no phase 3 trials have been made.CASE SUMMARY A 63-year-old man was diagnosed in December 2016 with stage III B intrahepatic cholangiocarcinoma.Surgery was performed,followed by adjuvant chemotherapy treatment with capecitabine and gemcitabine;although,the gemcitabine was suspended due to allergic reaction after two cycles.In April 2019,metastatic cholangiocarcinoma relapse was diagnosed,and a first-line treatment with FOLFOX scheme was started.Eight cycles were administered,producing an initial clinical improvement and decrease in blood tumor marker levels.Radiological and serological progression was noted in September 2019.As a second-line treatment,FOLFIRI was not recommended due to risk of worsening the patient’s tumor-related diarrhea.A combination therapy with gemcitabine was not feasible,as the patient had previously suffered from an allergic reaction to this treatment.We decided to use nab-paclitaxel as a second-line treatment,and four cycles were administered.Both clinical and serological responses were observed,and a radiological mixed response was also noted.CONCLUSION Advanced cholangiocarcinoma could be treated with nab-paclitaxel monotherapy,which should be studied in combination with other types of treatment(chemotherapy,fibroblast growth factor receptor inhibitors).

Short-term outcomes of albumin-bound paclitaxel (abraxane)-containing chemotherapy in patients with advanced gastric cancer: a report of 14 cases

Objective： Albumin-bound paclitaxel （abraxane, ABX） has more favorable efficacy and less toxicity than conventional taxanes. However, the data of ABX in advanced gastric cancer （AGC） treatment is unavailable. The current study was designed to summarize our experience in treating AGC patients with ABX. Methods： The clinical data of patients with AGC who had received at least one cycle of ABX-based chemotherapy in Sun Yat-sen University Cancer Center from January 10th 2010 to May 14th 2012 was retrospectively analyzed. Results： A total of 47 cycles of ABX-containing regimens, with a median of 3 cycles （range： 1-8 cycles）, were administered to 14 patients. Five （35.7%） partial responses and 6 （42.9%） stable diseases were obtained, with a disease control rate （DCR） of 78.6%. The median progression free survival （PFS） and overall survival （OS） were 3.3 and 10.8 months, respectively. Interestingly, patients in the first-line setting achieved a DCR of 100% （8/8）. Neutropenia and thrombocytopenia were the main grade 3/4 adverse events with an incidence of 50% in the whole group. However, only 25% patients （2/8） experienced grade 3 neutropenia when ABX in combination with fluoropyrJmJdines. Conclusion： The activity of ABX-based regimens as first-line therapy for patients with AGC is remarkable, and the toxicity is mild when ABX combined with fluorepyrimidines. Further prospective clinical trials of ABX-based chemotherapy as first-line treatment for AGC are strongly anticipated.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

Weekly intravenous nanoparticle albumin-bound paclitaxel for elderly patients with stage IV non-small-cell lung cancer:a series of 20 cases

The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.

Induction chemotherapy with albumin-bound paclitaxel plus lobaplatin followed by concurrent radiochemotherapy for locally advanced esophageal cancer

BACKGROUND Albumin-bound paclitaxel(ABP)has been used as second-and higher-line treatments for advanced esophageal cancer,and its efficacy and safety have been well demonstrated.Lobaplatin(LBP)is a third-generation platinum antitumor agent;compared with the first two generations of platinum agents,it has lower toxicity and has been approved for the treatment of breast cancer,small cell lung cancer,and chronic granulocytic leukemia.However,its role in the treatment of esophageal cancer warrants further investigations.AIM To investigate the efficacy and safety of induction chemotherapy with ABP plus LBP followed by concurrent radiochemotherapy(RCT)for locally advanced esophageal cancer.METHODS Patients with pathologically confirmed advanced esophageal squamous cell carcinoma(ESCC)at our hospital were enrolled in this study.All patients were treated with two cycles of induction chemotherapy with ABP plus LBP followed by concurrent RCT:ABP 250 mg/m^(2),ivgtt,30 min,d1,every 3 wk;and LBP,30 mg/m^(2),ivgtt,2 h,d1,every 3 wk.A total of four cycles were scheduled.The dose of the concurrent radiotherapy was 56-60 Gy/28-30 fractions,1.8-2.0 Gy/fraction,and 5 fractions/wk.RESULTS A total of 29 patients were included,and 26 of them completed the treatment protocol.After the induction chemotherapy,the objective response rate(ORR)was 61.54%,the disease control rate(DCR)was 88.46%,and the progressive disease(PD)rate was 11.54%;after the concurrent RCT,the ORR was 76.92%,the DCR was 88.46%,and the PD rate was 11.54%.The median progression-free survival was 11.1 mo and the median overall survival was 15.83 mo.Cox multivariate analysis revealed that two cycles of induction chemotherapy followed by concurrent RCT significantly reduced the risk of PD compared with two cycles of chemotherapy alone(P=0.0024).Non-hematologic toxicities were tolerable,and the only grade 3 non-hematologic toxicity was radiation-induced esophagitis(13.79%).The main hematologic toxicity was neutropenia,and no grade 4 adverse event occurred.CONCLUSION Induction chemotherapy with ABP plus LBP followed by concurrent RCT is effective in patients with locally advanced ESCC,with mild adverse effects.Thus,this protocol is worthy of clinical promotion and application.

Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to theimpaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile,acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1(PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps,we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer withmitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF-bdual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase(AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugatingmitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembledwith albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticleseffectively decreased the expression of collagen in vitro, which then led to the enhanced accumulation ofPTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF-b in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cellinfiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy toinhibit PTX@Alb-resistant tumors, further supporting its better clinical application。

Hemorrhagic cystitis in gastric cancer after nanoparticle albuminbound paclitaxel:A case report

BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.

3-Methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell

Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.

Paclitaxel induces human KOSC3 oral cancer cell apoptosis through caspase pathways

Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.

Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer:a multicenter,open-label,non-inferiority,randomized controlled trial

Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.

Ganoderma lucidum spore oil enhances the effect of paclitaxel,improves the tolerance to paclitaxel and prolongs the survival in Lewis tumor-bearing mice

Purpose:This study aims to investigate whether Ganoderma lucidum spore oil(GLSO)could enhance the effect of paclitaxel(PTX),improve the tolerance to PTX and prolong the overall survival of Lewis tumor-bearing mice,which has never been reported before.Methods:The tumor,spleen,and thymus were weighed at the end of the experiment.Whole blood was collected for hematological index analysis,and the intact femur was removed to determine the bone marrow nucleated cell count(BMN).The percentage of lymphocytes in the spleen of mice was detected by flow cytometry,the activity of NK cells was detected by LDH assay,and the proliferation index of lymphocytes was determined by CCK-8 assay.The overall and mean survival time and life extension rate were calculated using SPSS software.Results:Our data showed that GLSO could enhance the anti-tumor effect of PTX and prolong the survival of mice.The underlying mechanisms of the above effects might be related to the toxic reduction effect of GLSO by relieving hematotoxicity,myelosuppression and immunosuppression.Specifically,GLSO could increase the number of blood cells and bone marrow cells,alleviate the thymic index,and elevate the number and activity of NK cells in mice treated with PTX.Conclusion:GLSO may enhance the efficacy of PTX by boosting the activity of immune NK cells and prolong survival by counteracting PTX-induced bone marrow alterations and improving hematopoiesis.These findings suggested the promising role of GLSO in combination with PTX to extend the survival and increase the tolerance of patients in clinical chemotherapy of lung cancer.

卡瑞利珠单抗联合白蛋白紫杉醇治疗老年晚期三阴性乳腺癌对照研究

目的探讨卡瑞利珠单抗联合白蛋白紫杉醇治疗老年晚期三阴性乳腺癌(TNBC)患者的临床疗效。方法将80例老年晚期TNBC患者按照其治疗意愿分为观察组和对照组,每组各40例。对照组患者采用白蛋白紫杉醇治疗,观察组患者在对照组基础上联合卡瑞利珠单抗治疗,21 d为1个治疗周期,两组均持续治疗6个周期。比较两组患者临床疗效、毒副反应发生情况、1 a生存率及治疗前后血清肿瘤标志物[癌胚抗原(CEA)、糖类抗原153(CA153)、血管内皮生长因子(VEGF)]水平、生活质量[乳腺癌患者生命质量测定量表(FACT-B)评分]。结果观察组患者疾病控制率高于对照组(P<0.05)。治疗后,观察组患者血清CEA、CA153、VEGF水平低于对照组,FACT-B总分及生理状况、情感状况、功能状况维度评分高于对照组(P<0.01)。两组患者骨髓抑制、恶心呕吐、心脏毒性、肝功能异常、肾功能异常等毒副反应发生情况比较,差异无统计学意义(P>0.05)。两组患者1 a生存率比较,差异无统计学意义(P>0.05)。结论卡瑞利珠单抗联合白蛋白紫杉醇治疗老年晚期TNBC疗效较好,可有效降低患者血清肿瘤标志物水平,提高患者的生活质量,且不会增加毒副作用。

PD-L1单抗加强紫杉醇联合香菇多糖体外抗人乳腺癌MDA-MB-231作用

目的 探讨程序性细胞死亡-配体1(PD-L1)单抗、紫杉醇(PTX)联合香菇多糖(LNT)体外对人乳腺癌细胞(MDA-MB-231)的作用。方法 将MDA-MB-231、人外周血单个核细胞(PBMC)和MDA-MB-231+PBMC共培养,随机分为对照组、PTX组、LNT组、MPDL3280A(PD-L1单抗)组、PTX+LNT组和PTX+LNT+MPDL3280A组。采用CCK8检测细胞的活性;流式细胞术检测MHC-I和PD-L1的表达;ELISA试剂盒检测IFN-γ和TNF-α的含量。结果 与对照组相比,PTX组、MPDL3280A组、PTX+LNT组及PTX+LNT+MPDL3280A组显著抑制MDA-MB-231的活性(P<0.01);LNT组和PTX+LNT+MPDL3280A组显著促进PBMC的免疫作用(P<0.05,P<0.01);PTX+LNT+MPDL3280A组显著抑制MDA-MB-231+PBMC共培养MDA-MB-231的活性(0.56±0.16 vs. 0.39±0.13,P<0.05);LNT显著促进MDA-MB-231上PD-L1的表达和PBMC分泌IFN-γ(P<0.05)。结论 PD-L1单抗通过阻断PD-L1与PD-1之间的作用,提高免疫,促进PTX联合LNT的体外抗三阴性乳腺癌作用。

奥拉帕利联合一线化疗在铂敏感复发性上皮性卵巢癌患者中的应用

目的分析奥拉帕利联合一线化疗(紫杉醇+卡铂)在铂敏感复发性上皮性卵巢癌(ROC)患者中的应用效果。方法本研究采用前瞻性随机对照分析,纳入2021年6月至2022年6月河南科技大学第一附属医院收治的80例铂敏感ROC患者为研究对象,根据随机、双盲的原则分为观察组[40例,一线化疗(紫杉醇+卡铂)方案+安慰剂+奥拉帕利]和对照组[40例,一线化疗方案+安慰剂],两组均持续治疗直至疾病进展或发生不可接受的不良反应。比较两组临床疗效、生存情况以及治疗期间不良反应发生情况。结果观察组客观缓解率及疾病控制率高于对照组(P<0.05);经Kaplan-Meier生存分析显示,观察组中位无进展生存期(PFS)、中位总生存期(OS)长于对照组(P<0.001);两组不良反应程度比较,差异无统计学意义(P>0.05)。结论相较于单纯的TC方案化疗,奥拉帕利联合TC方案在铂敏感ROC患者中应用效果更好,可有效延长患者生存期,且产生的3级及以上的不良反应较少。

不同紫杉醇类化疗药物对既往接受过治疗的晚期非小细胞肺癌患者的疗效比较

目的回顾性评估纳米白蛋白结合型紫杉醇(nab-PC)与常规紫杉醇类药物在接受过治疗的非小细胞肺癌患者(NSCLC)中的有效性。方法纳入既往接受过治疗的晚期NSCLC患者,这些患者在后续治疗中接受了不同类型紫杉醇治疗,包括溶剂型紫杉醇(sb-PC)、多西他赛、脂质体紫杉醇和nab-PC。接受了前三种常规紫杉醇治疗的患者被归为其他-PC组,接受了nab-PC治疗的患者被归为nab-PC组。主要终点指标为无进展生存期(PFS)和总生存期(OS)。结果研究最终纳入258例NSCLC患者,其中nab-PC组83例,其他-PC组175例。nab-PC组肺鳞状细胞癌患者的比例较高(48.2%vs.32.6%,P<0.05)。与其他-PC组相比,nab-PC组在客观缓解率(ORR)(42.2%vs.27.4%,P=0.018)和OS(14.7个月vs.11.8个月,P=0.003)方面均表现出显著改善,而PFS差异无统计学意义(P>0.05)。基于组织学的进一步分层分析显示,nab-PC的益处主要表现在肺鳞状细胞癌患者中。结论在既往接受过治疗的NSCLC患者中,后续治疗采用nab-PC相比于常规紫杉醇具有更优的ORR和OS,这一优势在肺鳞状细胞癌患者中更为明显。

紫杉醇(Paclitaxel)治疗晚期鼻咽癌的临床研究

评价紫杉醇对晚期鼻咽癌的客观疗效及毒副反应。方法 :采用紫杉醇175mg/m2,3h静脉滴注 (每3周1次 )方案共治疗晚期鼻咽癌病人22例 ,所有病人均接受两个疗程以上的化疗。结果 :22例病人均可评价疗效 ,有7例病人达到PR ,有效率为31 .82 %。主要毒副反应为骨髓抑制、恶心和呕吐、肌痛和关节痛、脱发等。大部分病人为Ⅰ～Ⅱ度反应 ,病人耐受良好。经常规预防用药后 ,未观察到有严重的过敏反应。结论 :紫杉醇是一种对晚期鼻咽癌有效的化疗药物 ,该剂量的紫杉醇临床使用较为安全 ,值得进一步的临床研究。

Preparation,physicochemical characterization and cyctotoxicity of solid dispersion of paclitaxel and polyvinylpyrrolidone

The objective of this study was to prepare and characterize paclitaxel-polyvinylpyrrolidone （PTX-PVP） solid dispersions with the intention of improving its solubility and dissolution properties. The PTX-PVP solid dispersion systems were prepared by solvent method. The release rate ofpaclitaxel was determined from dissolution studies and the physicochemical properties of solid dispersion were investigated by differential scanning calorimetry （DSC）, powder X-ray diffraction （PXRD） and scanning electron microscopy （SEM）. The cytotoxicities ofpaclitaxel in solid dispersion to the SKOV-3 cells were assayed by a SRB staining method. The results showed that the solubility and dissolution rate of paclitaxel were significantly improved in solid dispersion system compared with that of the pure drug and physical mixture. The results of DSC and PXRD showed that the paclitaxel in solid dispersion was amorphous form. No paclitaxel crystals in the solid dispersions was found during SEM analysis. Cytotoxicity study suggested that the inhibitory rates of PTX-PVP solid dispersion to SKOV-3 cells were higher than that of pure paclitaxel. The solubility and dissolution of paclitaxel were improved by solid dispersion technique. In vitro cytotoxicity of paclitaxel in solid dispersion was higher than that of pure drug.

活性氧响应型甲氨蝶呤修饰紫杉醇/淫羊藿苷胶束的工艺优化与体外抗肿瘤作用评价

目的 制备活性氧(ROS)响应型甲氨蝶呤(MTX)修饰紫杉醇(PTX)/淫羊藿苷(ICA)胶束(MTX-oxi-Ms@PTX/ICA),并对其进行工艺优化和体外抗肿瘤作用评价。方法 通过协同毒性实验筛选PTX和ICA的协同毒性浓度范围。采用薄膜水合法制备胶束,通过响应面法优化其工艺,并评估按最优工艺制备的胶束的基本特性。考察胶束对小鼠肾癌细胞RENCA的细胞毒性、靶向性以及抑制侵袭和迁移的作用。结果 协同毒性实验结果表明,PTX浓度为2.5~10μmol/L、ICA浓度为5~15μmol/L时表现出最强的协同毒性效果。MTX-oxi-Ms@PTX/ICA的最优工艺如下:聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物(Soluplus@)质量为80 mg,Soluplus@和维生素E琥珀酸酯聚乙二醇1000质量比为4∶1(mg/mg),二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000-酮缩硫醇-聚乙二醇5000为2 mg,二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000-甲氨蝶呤为2 mg,PTX为1 mg,ICA为1.5 mg,水合温度35℃,处方量为5 mL。最优工艺条件下,3批MTX-oxi-Ms@PTX/ICA中2个药物的平均包封率为92.75%;其临界胶束浓度为0.007 9 mg/mL,粒径为(62.09±1.68) nm,多分散性指数为0.046±0.032,Zeta电位为(-2.47±0.15) mV;放置30 d内,胶束粒度和多分散性指数均未发生明显变化;体外释放结果表明,MTX-oxi-Ms@PTX/ICA能够在氧化环境中更快地响应并释放药物。MTX-oxi-Ms@PTX/ICA对RENCA细胞的半数抑制浓度为(5.170±0.036)μmol/L;体外细胞摄取实验结果表明,与未修饰胶束相比,经MTX修饰的胶束对癌细胞具有更强的靶向效果,且其对RENCA细胞侵袭、迁移的抑制能力显著增强(P<0.05)。结论 成功制备了MTX-oxi-Ms@PTX/ICA胶束,该胶束具有较高的包封率、较低的临界胶束浓度和良好的稳定性;且其对RENCA细胞有较明显的细胞毒性,并具有抑制癌细胞侵袭、迁移的作用。

紫杉醇(Paclitaxel,紫素)治疗恶性肿瘤Ⅲ期临床研究报告

为了对紫杉醇的临床应用价值和药物不良反应进行进一步评价，根据协作组共同制定的Ⅲ期临床试用计划通过前瞻性多中心１６单位进行临床研究。共收治２４３例恶性肿瘤患者，均为有病理或细胞学证实的中晚期病人。单药治疗：所选病人大多为一般状况较好，首次治疗的晚期患者。应用紫杉醇１５０～１７５理学ｍｇ·ｍ－２，静脉滴注，３～５ｈ，每３～４周一次，２～３周期为一疗程。联合化疗主要为经手术、化疗、放疗后的晚期患者，所用方案为：紫杉醇静脉滴注１３５ｍｇ·ｍ－２，卵巢癌加顺铂８０ｍｇ·ｍ－２；乳腺癌加阿霉素４０ｍｇ·ｍ－２；肺癌加顺铂８０ｍｇ·ｍ－２或静脉滴注卡铂３５０ｍｇ·ｍ－２；食管癌加静脉滴注顺铂８０ｍｇ·ｍ－２，第１周和平阳霉素８ｍｇ，肌注２周，第１、２周使用。均每３周重复一次，２～３周期为一个疗程。结果本组可统计近期疗效的１９０例，治后完全缓解１４例，部分缓解７３例，无变化７７例，进展２６例，总有效率为４５．８％。卵巢癌单药治疗的有效比为３／４，与顺铂联合应用的有效率为３０％（６／２０）；乳腺癌单药治疗为６２．５％（１０／１６），与阿霉素联合应用为６０．０（２４／４０）；食管癌单用有效比为４／５，与顺铂及平阳霉素联合应用为?