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Medical Oncology (Northwood, London,... Jan 2015The aim of the study was to evaluate the efficacy and safety of intratumoral chemotherapy with paclitaxel liposome combined with systemic chemotherapy as induction... (Clinical Trial)
Clinical Trial
Intratumoral chemotherapy with paclitaxel liposome combined with systemic chemotherapy: a new method of neoadjuvant chemotherapy for stage III unresectable non-small cell lung cancer.
The aim of the study was to evaluate the efficacy and safety of intratumoral chemotherapy with paclitaxel liposome combined with systemic chemotherapy as induction therapy in clinical stage III unresectable non-small cell lung cancer (NSCLC). Between January 2011 and July 2014, 48 patients, stage III, performance status 0-1, with unresectable clinical stage IIIA or IIIB NSCLC suitable for definitive radiation treatment, were included in the study. Patients with T3N1M0 and T4 (ipsilateral lung nodules) N0-1M0 were not included. Patients were given 3 cycles of chemotherapy every 3 weeks. Carboplatin (AUC5 by i.v. on day 1) and gemcitabine (i.v. 1,000 mg/m(2) on days 1 and 8) were administered. Paclitaxel liposome was injected at 1-3 mg/ml concentration into the tumor lesion by computed tomography-guided percutaneous fine-needle intratumoral injection and proven malignant lymph nodes according to pretreatment histological/cytological results by endobronchial ultrasound drug delivery with a needle on day 1 and day 8. Toxicity was assessed on days 8 and 22 in each cycle. Overall response rate (ORR) evaluation was performed at the end of cycle 3. Out of the 48 enrolled patients, 28 were males and 20 females, 19 patients had stage IIIA and 29 stage IIIB NSCLC. Thirty-six partial responses and two complete responses were observed, for an ORR of 81 %. The most frequent G3-G4 toxicity included neutropenia (in 15 % of cases), hypertransaminasemia (6 %), and diarrhea (4 %). A median PFS of 16.5 months (95 % CI 13.7-19.2) and median OS of 23.2 months (95 % CI 20.0-26.3) were observed. Eleven stage IIIA patients underwent surgery, for a resection rate of 58 %. Intratumoral chemotherapy with paclitaxel liposome combined with systemic chemotherapy demonstrated a considerable disease response and resection rate, with acceptable toxicity.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Female; Humans; Injections, Intralesional; Kaplan-Meier Estimate; Liposomes; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Paclitaxel; Gemcitabine
PubMed: 25429832
DOI: 10.1007/s12032-014-0345-5 -
Drug Research Nov 2013Lipusu is the first paclitaxel liposome preparation approved in the world and has been widely used in China for the treatment of ovary, breast and non-small cell lung...
Lipusu is the first paclitaxel liposome preparation approved in the world and has been widely used in China for the treatment of ovary, breast and non-small cell lung cancer. In present study we evaluated the pharmacokinetic and tissue distribution characteristics of paclitaxel liposome in Sprague-Dawley rats and Beagle dogs. A rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for the determination of paclitaxel in plasma and tissues. The plasma concentrations of paclitaxel in both rats and dogs initially declined steeply, followed by slow elimination after intravenous administration of Lipusu at 5 mg/kg and 1 mg/kg, respectively. The pharmacokinetic parameters calculated by a non-compartmental method in rats and dogs were as follows: AUC0-24: 3 566.5±1 366.1 and 443.2±165.7 μg · h/L, CL: 1.5±0.5 and 2.1±0.6 L/h/kg, Vd: 20.0±7.8 and 38.4±12.5 L/kg, t1/2: 9.3±2.9 and 14.1±6.9 h, respectively. Biodistribution results in rats showed that except for brain and testis, liposomal paclitaxel was extensively distributed into various tissues, especially highly in liver and spleen.
Topics: Animals; Antineoplastic Agents, Phytogenic; Chromatography, Liquid; Dogs; Female; Liposomes; Male; Paclitaxel; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Tissue Distribution
PubMed: 23842945
DOI: 10.1055/s-0033-1349126 -
Journal of Biomedical Nanotechnology Aug 2018Liposome-microbubble complexes (LMC) have become a promising therapeutic carrier for ultrasound-triggered local drug release. However, it is still desirable for the...
Liposome-microbubble complexes (LMC) have become a promising therapeutic carrier for ultrasound-triggered local drug release. However, it is still desirable for the released drugs to be delivered to tumors as effectively as possible. Here, we fabricated iRGD-targeted paclitaxel-loaded liposome-microbubble complexes (iRGD-PTX-LMC) and investigated the feasibility of enhancing the local drug delivery to breast tumors by using these complexes along with ultrasound irradiation. Our results showed that iRGD-modified PTX-loaded liposomes (iRGD-PTX-PL) were successfully conjugated to the surface of microbubbles (MBs) through biotin-avidin linkage. The resulting iRGD-PTX-LMC retained the ultrasound imaging capability and showed effective ultrasound-triggered drug release. High cell affinity and enhanced drug delivery into tumor cells was confirmed for iRGD-PTX-LMC upon ultrasound exposure. Additionally, our data revealed that iRGD-PTX-LMC with ultrasound had a significantly better tumor growth inhibition effect than iRGD-PTX-PL or nontargeted PTX-LMC in not only in vitro but also in vivo studies. Histological examination indicated that the inhibition of tumor growth was caused by the increases in the drug concentration and the number of apoptotic tumor cells in tumor xenografts. In conclusion, our study revealed the great potential of iRGD-PTX-LMC as a new tool to enhance local drug delivery and significantly improve antitumor efficacy.
Topics: Breast Neoplasms; Cell Line, Tumor; Drug Delivery Systems; Humans; Liposomes; Microbubbles; Paclitaxel; Ultrasonography
PubMed: 29903054
DOI: 10.1166/jbn.2018.2594 -
Breast Cancer Research and Treatment Nov 2020Paclitaxel-based regimens are widely used in the neoadjuvant therapy (NAT) of breast cancer. The purpose is to analysis the efficacy and adverse events (AEs) among...
BACKGROUND AND PURPOSE
Paclitaxel-based regimens are widely used in the neoadjuvant therapy (NAT) of breast cancer. The purpose is to analysis the efficacy and adverse events (AEs) among common paclitaxel (PTX), docetaxel and liposomal paclitaxel. At the same time, we want to analysis the axillary nodal pathologic complete response (apCR) after NAT among the three groups.
METHODS
From April 2014 to 2020, 647 breast cancer patients underwent operation after NAT were included in this study. Patients received full course of anthracycline- and paclitaxel-based chemotherapy before surgery. The paclitaxel-based regimens included PTX, docetaxel and liposomal paclitaxel. The therapy efficacy and AEs of the three groups were evaluated. At the same time, the apCR was also analyzed.
RESULTS
In general, 30.6% (198/647) of patients achieved breast pathologic complete response (bpCR), which was 28.6%, 28.3% and 39.3% among PTX, docetaxel and liposomal paclitaxel group, respectively (p = 0.067). The total pathologic complete response (tpCR) (achieving both bpCR and apCR) was 21.6% (140/647). The tpCR was 13.3%, 19.4% and 34.4% among PTX, docetaxel and liposomal paclitaxel group, respectively (p = 0.026). The multivariate logistic analysis result showed that clinical tumor stage and molecular subtype were significantly associated with tpCR (all p < 0.05). Among 592 clinical positive patients (cN), the apCR was 39.0% (231/592). The multivariate logistic analysis showed that paclitaxel- based regimens and molecular subtype were indicated as independent predictors for apCR of NAT. The apCR was significantly higher in liposomal paclitaxel group (63.5%) than in PTX (24.6%) and docetaxel group (34.8%) (p < 0.001). The subgroup analysis among different molecular subtypes found that in triple negative (TN) and HER-2 positive (HER2+) subgroup, the apCR in liposomal paclitaxel group was significantly higher than those in PTX and docetaxel group (all p < 0.05). But no significant result was found in the subgroup analysis in hormone receptor positive/HER-2 negative subgroup (p = 0.050). Safety analysis indicated that the incidence of neutropenia (grade III-IV) and peripheral neurotoxicity (grade I-II) was significantly lower in the liposomal paclitaxel group than in the PTX and docetaxel group. The incidence of oral mucositis, anaphylaxis and palmar-plantar erythrodysesthesia syndrome was also much lower in liposomal paclitaxel than other two groups (all p < 0.05). And there was no significant difference in other AEs among the three groups (all p > 0.05).
CONCLUSION
Liposome paclitaxel had similar tumor suppressor effect compared with PTX and docetaxel in NAT setting. Moreover, it had a better axillary lymph node (ALN) response after NAT than PTX and docetaxel. These patients who received liposome paclitaxel had more chance to avoid ALN dissection after NAT. At the same time, the application of liposome enables liposome paclitaxel could significantly reduce AEs caused by chemotherapy. Therefore, we suggested the application of liposome paclitaxel in the NAT setting, especially for cN patients with TN and HER2 + disease.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Docetaxel; Female; Humans; Neoadjuvant Therapy; Paclitaxel; Receptor, ErbB-2
PubMed: 32776291
DOI: 10.1007/s10549-020-05851-8 -
Analytical Biochemistry Jan 2005A liquid chromatography-tandem mass spectrometry assay to quantify total paclitaxel in mouse plasma and tissue homogenates containing paclitaxel, Taxol, or...
Paclitaxel quantification in mouse plasma and tissues containing liposome-entrapped paclitaxel by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetics study.
A liquid chromatography-tandem mass spectrometry assay to quantify total paclitaxel in mouse plasma and tissue homogenates containing paclitaxel, Taxol, or liposome-entrapped paclitaxel-easy to use (LEP-ETU) was developed and validated. Docetaxel was used as the internal standard (IS). Liquid-liquid extraction with tert-butyl methyl ether was used for plasma sample preparation, and a one-step protein precipitation with acetonitrile containing 0.1% acetic acid was developed for tissue homogenates. Paclitaxel and IS are separated on a 50 x 2.1-mm C18 column and quantified using a triple-quadrupole mass spectrometer operating in positive ion electrospray multiple reaction monitoring mode, with a total run time of 3.5 min. The peak area of the m/z 854.4--> 286.2 transition of paclitaxel is measured versus that of the m/z 808.5--> 527.5 transition of IS to generate the standard curve. In plasma, the linear range is 0.2-500 ng/mL and could be extended by dilution to 100,000 ng/mL with acceptable precision and accuracy (< or = 15%). The lower limit of quantification is 0.5 ng/mL in tissue homogenates (10 ng/g tissue), and the standard curve is linear up to 1000 ng/mL, with precision and accuracy < or = 15%. This assay was used to support a pharmacokinetics and tissue distribution study of LEP-ETU in mice.
Topics: Animals; Chromatography, Liquid; Freezing; Indicator Dilution Techniques; Liposomes; Male; Mass Spectrometry; Mice; Molecular Structure; Paclitaxel; Reference Standards; Sensitivity and Specificity; Temperature
PubMed: 15620886
DOI: 10.1016/j.ab.2004.09.046 -
Drug Discovery Today Feb 2022The diterpenoid molecule paclitaxel (PTX), extracted from the Western yew tree, Taxus brevifolia, is a promising anticancer drug specifically in clinical use for ovarian... (Review)
Review
The diterpenoid molecule paclitaxel (PTX), extracted from the Western yew tree, Taxus brevifolia, is a promising anticancer drug specifically in clinical use for ovarian and breast cancers. However, its wider use is hampered by adverse effects and emerging resistance in cancer cells. Micelles, liposomes, cubosomes, and lipid nanoparticles (LNPs) have the potential to reduce or even remove complications associated with the use of PTX. Herein, we provide an overview of micro- and nanoformulations of PTX based on micelles, liposomes, cubosomes and LNPs to improve the therapeutic effects of this drug both in vitro and in vivo.
Topics: Cell Line, Tumor; Drug Carriers; Humans; Liposomes; Micelles; Nanoparticles; Paclitaxel; Polyethylene Glycols
PubMed: 34688912
DOI: 10.1016/j.drudis.2021.10.007 -
Nanoscale Aug 2015Real-time diagnosis and monitoring of disease development, and therapeutic responses to treatment, are possible by theranostic magnetic resonance imaging (MRI). Here we...
Real-time diagnosis and monitoring of disease development, and therapeutic responses to treatment, are possible by theranostic magnetic resonance imaging (MRI). Here we report the synthesis of a multifunctional liposome, which contains Gd-DOTA (an MRI probe), paclitaxel and c(RGDyk) (a targeted peptide). This nanoparticle overcame the insolubility of paclitaxel, reduced the side effects of FDA-approved formulation of PTX-Cre (Taxol®) and improved drug delivery efficiency to the tumor. c(RGDyk) modification greatly enhanced the cytotoxicity of the drug in tumor cells A549. The T1 relaxivity in tumor cells treated with the targeted liposome formulation was increased 16-fold when compared with the non-targeted group. In vivo, the tumors in mice were visualized using T1-weighted imaging after administration of the liposome. Also the tumor growth could be inhibited well after the treatment. Fluorescence images in vitro and ex vivo also showed the targeting effect of this liposome in tumor cells, indicating that this nanovehicle could limit the off-target side effects of anticancer drugs and contrast agents. These findings lay the foundation for further tumor inhibition study and application of this delivery vehicle in cancer therapy settings.
Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Survival; Contrast Media; Drug Carriers; Fluorescent Dyes; Heterocyclic Compounds; Humans; Liposomes; Magnetic Resonance Imaging; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Confocal; Nanostructures; Neoplasms; Oligopeptides; Organometallic Compounds; Paclitaxel; Polyethylene Glycols; Radiography; Transplantation, Heterologous
PubMed: 26022345
DOI: 10.1039/c5nr02144h -
Zhonghua Zhong Liu Za Zhi [Chinese... Jul 2011To compare the efficacy, side effects and influence of two chemotherapy regimens, paclitaxel liposome combined with platinum and paclitaxel combined with platinum, on... (Comparative Study)
Comparative Study Randomized Controlled Trial
[A randomized controlled trial of two chemotherapy regimens (paclitaxel liposome combined with platinum and paclitaxel combined with platinum) in concurrent chemoradiotherapy for cervical carcinoma].
OBJECTIVE
To compare the efficacy, side effects and influence of two chemotherapy regimens, paclitaxel liposome combined with platinum and paclitaxel combined with platinum, on the survival rate in patients with cervical carcinoma receiving concurrent chemoradiotherapy.
METHODS
One hundred and sixty two cases with primary cervical carcinoma diagnosed and treated in the Jiangxi Maternal and Children Hospital between January 2008 and November 2009 were enrolled in this randomized controlled trial. Seventy one cases were included in the paclitaxel group and 91 in the paclitaxel liposome group. The chemotherapy doses were as followings: paclitaxel liposome and paclitaxel 135 mg/m(2); cisplatin 80 mg/m(2) or carboplatin AUC 4 - 6, repeated every 21 days for two or three times. Radical radiotherapy was given to both groups at the same time. The efficacy was evaluated by the tumor regression and the patients were followed-up for six months.
RESULTS
The overall response rates of paclitaxel group and paclitaxel liposome group were 90.1% and 89.0%, respectively (P > 0.05). The 1-year cumulative survival rate was 91.4% for the paclitaxel group and 89.2% for the paclitaxel liposom group (P > 0.05). The incidence rate of adverse effects such as rash, gastrointestinal toxicity, bone marrow suppression and muscle/joint pain in the paclitaxel liposome group was significantly lower than that in the paclitaxel group (P < 0.05), while there was no significant difference regarding the hair loss, liver damage, and peripheral neuritis (P > 0.05).
CONCLUSIONS
Paclitaxel liposome plus platinum is a safe and effective therapeutic regimen for stage IIa-IV cervical carcinoma. However, the long-term efficacy of this regimen should be further observed.
Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carboplatin; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Cobalt Radioisotopes; Exanthema; Female; Follow-Up Studies; Gastrointestinal Diseases; Humans; Iridium Radioisotopes; Liposomes; Middle Aged; Neoplasm Staging; Paclitaxel; Remission Induction; Survival Rate; Uterine Cervical Neoplasms
PubMed: 22093629
DOI: No ID Found -
Zhongguo Fei Ai Za Zhi = Chinese... Feb 2012The third generation single-agent drug has been recommended as a first-line chemotherapy for elderly patients with advanced non-small cell lung cancer (NSCLC). The aim... (Randomized Controlled Trial)
Randomized Controlled Trial
[A randomized clinical trial on the clinical efficacy and toxicities of single-agent paclitaxel liposome versus paclitaxel liposome plus oxaliplatin as first-line chemotherapy for advanced non-small cell lung cancer in elderly patients].
BACKGROUND AND OBJECTIVE
The third generation single-agent drug has been recommended as a first-line chemotherapy for elderly patients with advanced non-small cell lung cancer (NSCLC). The aim of the current radomized trial is to compare the clinical efficacy and toxicities of single-agent paclitaxel liposome versus paclitaxel liposome plus oxaliplatin as a first-line chemotherapy for elderly patients.
METHODS
Sixty-nine advanced NSCLC patients from July 2008 to August 2010, confirmed with pathology or cytology and had never received treatment, were randomly divided into two groups. The first group was given 135 mg/m² of single-agent paclitaxel liposome on day 1 of each cycle. The second group was given 135 mg/m² paclitaxel liposome plus 125 mg/m² oxaliplatin on day 1 of each cycle. One cycle is composed of 21 days. Efficacy and toxicities could be evaluated after two or more cycles.
RESULTS
No statistical differences were observed between the two groups in terms of efficacy (22.9% vs 35.3%, P=0.297), disease control rate (60.0% vs 70.6%, P=0.450), and 1-year survival rate (28.6% vs 41.2%, P=0.724). However, the group treated with paclitaxel liposome plus oxaliplatin had longer progression free survival (PFS) (5.0 months vs 3.5 months, P=0.024). In addition, the toxicities that occurred in the two groups were similar including leukocytopenia (P=0.808), thrombocytopenia (P>0.999), anemia (P=0.477), and nausea/vomiting (P=0.777). The number of neurotoxicity that occurred in the two groups were 33 and 3 (97.1% vs 8.6%, P<0.001), respectively. However, all were grade I-II.
CONCLUSIONS
The clinical efficacy of paclitaxel liposome plus oxaliplatin as a first-line chemotherapy for elderly patients with advanced NSCLC is more better than that of the single-agent paclitaxel liposome. It prolongs PFS and is safe for clinical use.
Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Female; Humans; Liposomes; Male; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Treatment Outcome
PubMed: 22336235
DOI: 10.3779/j.issn.1009-3419.2012.02.04 -
Chemistry and Physics of Lipids Jul 2018Liposomes can achieve a controlled release and an improved bioavailability of water- insoluble drug with minimized side effects. Paclitaxel is an efficient anticancer...
Surface modification of paclitaxel-loaded liposomes using d-α-tocopheryl polyethylene glycol 1000 succinate: Enhanced cellular uptake and cytotoxicity in multidrug resistant breast cancer cells.
Liposomes can achieve a controlled release and an improved bioavailability of water- insoluble drug with minimized side effects. Paclitaxel is an efficient anticancer drug for the treatment of various cancers. However, paclitaxel has a solubility of 0.5 mg/L in water and a low bioavailability of 6.5%. Moreover, paclitaxel is a substrate for p-glycoprotein, which shows a decreased accumulation of drug within the cancer cell expressed by a p-glycoprotein. Therefore, the purpose of this study is to prepare a paclitaxel-loaded liposome and evaluate the effect of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as an inhibitor of p-glycoprotein on the paclitaxel-loaded liposome. The paclitaxel-loaded liposome and TPGS coated paclitaxel-loaded liposome had spherical vesicles, with mean particle size 184.9 ± 18.45 nm with PDI 0.324 ± 0.018 and 282.6 ± 20.41 nm with PDI 0.269 ± 0.013, respectively. Paclitaxel-loaded liposome and TPGS coated paclitaxel-loaded liposome showed a controlled and sustained release of PTX over 72 h. The cellular uptake of paclitaxel from TPGS coated paclitaxel-loaded liposome was a 3.56-fold increase for 2 h and 5.75-fold increase for 4 h compared to that from paclitaxel-loaded liposome in MCF-7/ADR cells, resulting in improved cytotoxicity against MCF-7/ADR cells. Western blot assay revealed the P-gp inhibitory effect of TPGS-coated PTX-liposome. In conclusion, TPGS coated liposome with a sustained releasing capability and the inhibitory effect of p-glycoprotein may be a promising carrier for future applications in cancer therapy.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Survival; Drug Liberation; Drug Resistance, Neoplasm; Female; Humans; Liposomes; MCF-7 Cells; Microscopy, Confocal; Paclitaxel; Particle Size; Polysorbates; Solubility; Vitamin E
PubMed: 29550143
DOI: 10.1016/j.chemphyslip.2018.03.005