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 advance...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
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(na...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).展开更多
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...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.展开更多
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...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.展开更多
The electrochemical behavior of paclitaxel drug was studied at a glassy carbon electrode in phosphate buffer solutions using cyclic and differential-pulse voltammetric techniques.The oxidation process was shown to be ...The electrochemical behavior of paclitaxel drug was studied at a glassy carbon electrode in phosphate buffer solutions using cyclic and differential-pulse voltammetric techniques.The oxidation process was shown to be irreversible over the pH range(3.0e10.4)and was diffusion controlled.Effects of anodic peak potential(E_(p)),anodic peak current(Ipa),scan rate,pH,heterogeneous rate constant(k^(0)),etc have been discussed.A possible electrooxidation mechanism was proposed.An analytical method was developed for the determination of paclitaxel in phosphate buffer solution at pH¼7.0 as a supporting electrolyte.The anodic peak current varied linearly with paclitaxel concentration in the range 1.0×10^-(6)M to 1.0×10^-(5)M with a limit of detection(LOD)of 1.23×10^(-8)M and limit of quantification(LOQ)of 4.10×10^(-8)M.The proposed method was successfully applied to the determination of paclitaxel in pure and real samples.展开更多
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...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。展开更多
文摘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.
文摘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.
文摘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.
文摘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).
文摘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.
文摘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.
基金One of the author(J.I.Gowda)thanks UGC,New Delhi,for the award of Research Fellowship in Science for Meritorious Stu-dents(RFSMS).
文摘The electrochemical behavior of paclitaxel drug was studied at a glassy carbon electrode in phosphate buffer solutions using cyclic and differential-pulse voltammetric techniques.The oxidation process was shown to be irreversible over the pH range(3.0e10.4)and was diffusion controlled.Effects of anodic peak potential(E_(p)),anodic peak current(Ipa),scan rate,pH,heterogeneous rate constant(k^(0)),etc have been discussed.A possible electrooxidation mechanism was proposed.An analytical method was developed for the determination of paclitaxel in phosphate buffer solution at pH¼7.0 as a supporting electrolyte.The anodic peak current varied linearly with paclitaxel concentration in the range 1.0×10^-(6)M to 1.0×10^-(5)M with a limit of detection(LOD)of 1.23×10^(-8)M and limit of quantification(LOQ)of 4.10×10^(-8)M.The proposed method was successfully applied to the determination of paclitaxel in pure and real samples.
基金the National Natural Science Foundation of China(22377093)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR23C100001,China)the Zhejiang Qianjiang Talent Plan(QJD20020224,China).
文摘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。
