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Japanese Journal of Clinical Oncology Mar 2014This study is aimed to assess the efficacy and toxicity of weekly liposome-paclitaxel and S-1 combination therapy as first-line treatment for advanced gastric cancer.
OBJECTIVE
This study is aimed to assess the efficacy and toxicity of weekly liposome-paclitaxel and S-1 combination therapy as first-line treatment for advanced gastric cancer.
METHODS
The chemotherapy regime was 80 mg/m(2) liposome-paclitaxel given on days 1, 8, 15 and 22, combined with S-1 60 mg (body surface area > 1.5) or 50 mg (1.25 < body surface area < 1.5) twice a day on days 1-28, 6 weeks as one cycle. The patients continued to be treated until they received four cycles or until they developed either progressive disease or untolerated toxicity. The response rate, progression-free survival, overall survival and toxicity were evaluated.
RESULTS
A total of 56 patients were enrolled, and the median age was 60 years (range = 38-70 years; 39 males and 17 females). The response rate and disease control rate were 25% (14/56) and 87.5% (49/56), respectively. The median progression-free survival was 6.1 months (95% confidence interval: 5.0-7.2), and the median overall survival was 10.6 months (95% confidence interval: 7.2-14.0). The most frequent hematological toxicities were neutropenia and anemia, which occurred in 22 (48.9%) and 11 (19.6%) patients, respectively.
CONCLUSIONS
The weekly administration of a combined regimen of liposome-paclitaxel plus S-1 is effective and has a favorable toxicity profile for advanced gastric cancer.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Liposomes; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome
PubMed: 24453274
DOI: 10.1093/jjco/hyt212 -
Cancer Letters Oct 1996Paclitaxel, a recently approved antineoplastic agent, is cleared slowly from the peritoneal cavity after i.p. injection, and therefore appears to be promising for...
Paclitaxel, a recently approved antineoplastic agent, is cleared slowly from the peritoneal cavity after i.p. injection, and therefore appears to be promising for intracavitary therapy of malignancies confined to the peritoneal cavity. However the dose-limiting toxicity of Taxol, the clinical formulation of paclitaxel, was severe abdominal pain, likely caused by the excipients (Cremophor EL and ethanol) that are required to overcome low drug solubility. We tested the hypothesis that a liposome-based formulation could modulate paclitaxel toxicity independent of antitumor activity. The dose-dependence of toxicity and antitumor effect of paclitaxel liposomes was evaluated after i.p. administration against i.p. P388 leukemia. Liposomal paclitaxel showed antitumor activity similar to that of free paclitaxel (as Taxol), but was better tolerated by both healthy and tumor-bearing mice.
Topics: Animals; Antineoplastic Agents, Phytogenic; Drug Carriers; Drug Screening Assays, Antitumor; Female; Leukemia P388; Life Expectancy; Liposomes; Mice; Mice, Inbred DBA; Paclitaxel; Peritoneal Neoplasms
PubMed: 8947523
DOI: 10.1016/0304-3835(96)04380-7 -
Biomedicine & Pharmacotherapy =... Sep 2009To obtain an optimal premedication protocol for paclitaxel liposome (Lipusu) in the treatment of solid tumors. (Clinical Trial)
Clinical Trial
OBJECTIVE
To obtain an optimal premedication protocol for paclitaxel liposome (Lipusu) in the treatment of solid tumors.
METHODS
From February 2005 to September 2007, 53 patients with advanced non-small-cell lung cancer (16 cases), breast cancer (14 cases), esophagus cancer (six cases), gastric cancer (16 cases), head and neck cancer (one case) were recruited from the Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute. Lipusu was delivered at 175 mg/m(2) (triweekly or divided into weekly) as a component of combined chemotherapy. Several premedications were attempted (detailed in the text).
RESULTS
The toxicity profile of premedications included: insomnia (five cases), dysphoria (three cases), hyperglycemia (two cases), fatigue (two cases), abdominal distension (one case), and vertigo (one case). No treatment-related death occurred.
CONCLUSIONS
Our recommendations for the premedication of Lipusu in the treatment of solid tumors are: (1) methylprednisolone 40 mg, administered intravenously 30 min before Lipusu, and granisetron 30 min before chemotherapy, (2) dexamethasone 2.25-3 mg taken orally 12 h and 2 h before Lipusu, and granisetron 30 min before chemotherapy.
Topics: Administration, Oral; Adult; Aged; Anthracyclines; Antiemetics; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Dexamethasone; Drug Administration Schedule; Female; Fluorouracil; Glucocorticoids; Granisetron; Humans; Infusions, Intravenous; Liposomes; Male; Methylprednisolone; Middle Aged; Neoplasms; Paclitaxel; Premedication; Treatment Outcome; Young Adult
PubMed: 19019625
DOI: 10.1016/j.biopha.2008.10.001 -
Journal of Pharmaceutical Sciences Nov 2010We investigated the clinical pharmacokinetics of paclitaxel liposome with a new route of administration, which was intrapleural infusion, in nine advanced nonsmall-cell...
We investigated the clinical pharmacokinetics of paclitaxel liposome with a new route of administration, which was intrapleural infusion, in nine advanced nonsmall-cell lung cancer (NSCLC) patients with malignant pleural effusions after a single administration. Paclitaxel concentrations were measured in pleural fluid and plasma using a simple and rapid ultra performance liquid chromatography (UPLC) method following intra- and inter-day validations. In subjects, AUC(0-96 h) values in pleural fluid and plasma were 17831 ± 6439 µg h/mL and 778 ± 328 µg h/mL, respectively, and T(max) values were initial time and 6.67 h after administration and the corresponding C(max) values were 558 ± 44 µg/mL and 12.89 ± 6.86 µg/mL, respectively. The T(1/2,IP), CL(IP) and Vd(IP) values in pleural fluid were 76 ± 48 h, 0.005 ± 0.002 L/h m(2) and 0.53 ± 0.23 L/m(2), respectively. The T(1/2,pla), CL(pla), and Vd(pla) values in plasma were 68.34 ± 56.74 h, 0.184 ± 0.080 L/h m(2), and 17.53 ± 16.57 L/m(2), respectively. However, some paclitaxel concentrations from several patients in plasma could not be detected at some designed time-points. Our results might offer new opportunities to design and determine individually appropriate therapeutic dosage regimens based on a pharmacokinetic profile.
Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Area Under Curve; Carcinoma, Non-Small-Cell Lung; Chromatography, High Pressure Liquid; Drug Administration Routes; Humans; Linear Models; Liposomes; Middle Aged; Paclitaxel; Pleural Cavity; Pleural Effusion, Malignant; Sensitivity and Specificity
PubMed: 20845471
DOI: 10.1002/jps.22169 -
Molecular Biology Reports May 2022In this study, the optimized niosomal formulation containing paclitaxel using non-ionic surfactants and cholesterol was designed and its cytotoxic effects against...
BACKGROUND
In this study, the optimized niosomal formulation containing paclitaxel using non-ionic surfactants and cholesterol was designed and its cytotoxic effects against different breast cancer cell lines and apoptosis gene expression analysis were also investigated.
METHODS AND RESULTS
Due to enhancing equation variables, the Box-Behnken method has been applied. Lipid/drug molar ratio, the amounts of Span 60, and cholesterol were selected as the target for optimization. The particle size of niosome loaded paclitaxel and entrapment efficiency proportion have been considered in the role of dependent variables. Then the cytotoxic activity of the optimized formulation was evaluated using an MTT assay against different breast cancer cell lines including MCF-7, T-47D, SkBr3, and MDA-MB-231. The expression level of Bax and Bcl-2 apoptosis genes was determined by Real-Time PCR. In this study, the optimized niosomal formulation revealed that the synthesized niosomes had a spherical appearance and had an average size of 192.73 ± 5.50 nm so that the percentage of drug loading was 94.71 ± 1.56%. Moreover, this formulation showed a controlled and slowed release of paclitaxel at different pH (7.4, 6.5, and 5.4). The cytotoxicity results demonstrated that cell viability in all concentrations of niosome loaded paclitaxel had profound cytotoxic effects on all studied breast cancer cell lines compared to the free paclitaxel (p < 0.05). In addition, the expression of apoptosis genes was much higher than that of free paclitaxel indicating the susceptibility of cells to apoptosis.
CONCLUSIONS
As a result, niosomal formulations containing paclitaxel can be used as a new drug delivery system to increase cytotoxicity and treatment of breast cancer in the upcoming future.
Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cholesterol; Female; Gene Expression; Humans; Liposomes; MCF-7 Cells; Paclitaxel; Particle Size
PubMed: 35235156
DOI: 10.1007/s11033-022-07199-2 -
Surgical Oncology Sep 2022Breast cancer (BC) is a common malignant tumor. Apatinib in combination with other treatments has been used for BC; however, its safety and efficacy are not well-known.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Breast cancer (BC) is a common malignant tumor. Apatinib in combination with other treatments has been used for BC; however, its safety and efficacy are not well-known. Therefore, this meta-analysis was performed to assess the efficacy and safety of apatinib in the treatment of BC.
METHODS
Studies comparing the effects of apatinib-based therapy versus control among BC patients were included. On January 21, 2022, a systematic search was performed in 9 databases. The risk ratio (RR) with 95% confidence interval (CI) was used to estimate efficacy and safety. The I square value (I) was used to assess heterogeneity. A leave-one-out sensitivity analysis was also conducted. Publication bias was assessed by funnel plots and Egger's and Begg's tests.
RESULTS
A total of 31 studies including 2,258 BC patients were included. The results showed that apatinib group had a significant improvement in disease control rate (DCR, RR = 1.43, 95% CI = 1.35-1.52, I = 43.8%) and objective response rate (ORR, RR = 1.79, 95% CI = 1.51-2.13, I = 61.8%) compared to the control group. Except for hemorrhage, hypertension, and hand-foot syndrome, the adverse events were similar between apatinib group and control group. Subgroup analyses found statistically significant differences in DCR in all subgroups except for apatinib combined with radiation therapy and with paclitaxel liposome plus S1. For ORR, there were statistically significant differences in all subgroups except for the radiation therapy, and apatinib monotherapy subgroups.
CONCLUSIONS
Our study shown apatinib showed good efficacy and acceptable safety in the treatment of BC patients. More high-quality randomized controlled trials from different regions and countries are needed to confirm our findings.
Topics: Breast Neoplasms; Female; Humans; Liposomes; Paclitaxel; Pyridines; Treatment Outcome
PubMed: 35930900
DOI: 10.1016/j.suronc.2022.101818 -
Methods in Molecular Biology (Clifton,... 2010Liposomal doxorubicin and nab-paclitaxel are nanoparticle formulations of traditional cancer chemotherapy drugs which have ample clinical experience both pre- and... (Review)
Review
Liposomal doxorubicin and nab-paclitaxel are nanoparticle formulations of traditional cancer chemotherapy drugs which have ample clinical experience both pre- and post-nanoparticle modification. The alterations in pharmacokinetics, pharmacodynamics, efficacy, and toxicity compared with their parent compounds are instructive for future development of nanoparticle-based therapies. In this article we review the current status of these agents, emphasizing the alterations in clinical behavior resulting from the nanoparticle formulation of the parent compound.
Topics: Albumins; Doxorubicin; Humans; Liposomes; Nanomedicine; Nanoparticles; Neoplasms; Paclitaxel
PubMed: 20217610
DOI: 10.1007/978-1-60761-609-2_26 -
Breast (Edinburgh, Scotland) Feb 2014Nanoparticle-based drug delivery platforms are emerging as powerful chemotherapeutic modalities in breast cancer. Doxorubicin and paclitaxel nanoparticle formulations... (Review)
Review
Nanoparticle-based drug delivery platforms are emerging as powerful chemotherapeutic modalities in breast cancer. Doxorubicin and paclitaxel nanoparticle formulations are currently used clinically, yielding distinct pharmacokinetic parameters that prolong blood circulation times, enhance drug accumulation in tumors, and limit adverse side effects to patients. And while these nanoconstructs have shown substantial improvements in patient tolerability and survival, several emerging trends stand to make a significant impact on future generations of nanoparticle platforms for breast cancer therapy. Firstly, there is a heightened understanding of several processes involved in tumor growth, potentiation, and invasion, resulting in the identification of several attractive molecular targets. This in turn has given rise to antibody-based therapeutics, drug repositioning, and the burgeoning field of RNA interference (RNAi). Secondly, an enhanced understanding of transport phenomena involved in delivery of chemotherapeutics has led to a rethinking and retooling of nanoscale drug carrier designs. Nanoparticle platforms are now incorporating features meant to overcome biological barriers and enhance drug accumulation within tumors, all the while incorporating unique chemistries that enable for controlled release of therapeutic payloads. This review aims to detail the current clinical state of nanoparticle-based therapeutics in breast cancer, as well as highlight several platforms that exemplify the future generation of innovative approaches to chemotherapy in breast cancer.
Topics: Antineoplastic Agents; Breast Neoplasms; Doxorubicin; Drug Delivery Systems; Female; Humans; Liposomes; Micelles; Nanoparticles; Paclitaxel; Polymers; RNA Interference
PubMed: 24215984
DOI: 10.1016/j.breast.2013.10.006 -
Molecular Pharmaceutics Aug 2019Paclitaxel (PTX) is a microtubule-stabilizing agent widely used to treat breast cancer. Nevertheless, the low solubility of the drug and the side effects of commercial...
Paclitaxel (PTX) is a microtubule-stabilizing agent widely used to treat breast cancer. Nevertheless, the low solubility of the drug and the side effects of commercial formulations available limit its clinical use. In this way, our group recently described the preparation of PTX-loaded folate-coated long-circulating and pH-sensitive liposomes (SpHL-folate-PTX). Therefore, a proof-of-concept study was designed in order to demonstrate the feasibility of SpHL-folate-PTX against breast tumor cell line MDA-MB-231. Cellular uptake of the liposomes and PTX was evaluated. Apoptosis and cell cycle were analyzed by flow cytometry. In vivo antitumor activity was carried out in MDA-MB-231 tumor-bearing BALB/c nude mice. Cellular uptake assay showed a high cell delivery of PTX by SpHL-folate-PTX, which leads to superior cytotoxicity and activation of apoptosis pathways. The SpHL-folate-PTX treatment induces an expressive increase of cells in the G0/G1 phase compared to free PTX and SpHL-PTX (without folate). In vivo studies showed a significant reduction in the tumor growth and a lower uptake of a radiopharmaceutical in the scintigraphic images for the SpHL-folate-PTX group, suggesting its higher efficacy compared with free PTX and SpHL-PTX. Histomorphometric analyses demonstrated an increase in necrosis and inflammation areas in animals treated with SpHL-folate-PTX. A decrease in the proliferative cells and a higher percentage of apoptotic cells were observed by immunohistochemical analyses after the treatment with SpHL-folate-PTX. Therefore, the data confirmed the potential of SpHL-folate-PTX as an alternative antitumor therapy, especially for breast cancer.
Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Drug Compounding; Female; Folic Acid; G1 Phase Cell Cycle Checkpoints; Humans; Hydrogen-Ion Concentration; Liposomes; Mice; Paclitaxel; Proof of Concept Study; Radionuclide Imaging; Solubility; Xenograft Model Antitumor Assays
PubMed: 31257891
DOI: 10.1021/acs.molpharmaceut.9b00329 -
Zhonghua Zhong Liu Za Zhi [Chinese... May 2015The aim of this study was to analyze the efficacy and safety of paclitaxel liposomal and docetaxel for neoadjuvant chemotherapy of breast cancer.
OBJECTIVE
The aim of this study was to analyze the efficacy and safety of paclitaxel liposomal and docetaxel for neoadjuvant chemotherapy of breast cancer.
METHODS
We retrospectively analyzed the clinical data of 188 operable patients with breast cancer who received neoadjuvant chemotherapy. According to the treatment regimens, they were divided into the group of paclitaxel liposome (86 patients) and group of docetaxel (102 patients) treatment. All the patients received a combination therapy with epirubicin and cyclophosphamide, i.e. neoadjuvant chemotherapy with three drugs, 21 days as a cycle, and a total of 6 cycles. Surgery was carried out three weeks after the end of chemotherapy, and the chemotherapy efficacy and adverse reaction of both groups were evaluated.
RESULTS
Pathological complete response (pCR) rate in the paclitaxel liposome group and docetaxel group was 10.5% and 9.8%, respectively, the objective response rate (ORR) was 80.2% and 79.4%, respectively, and the disease control rate (DCR) was 95.3% and 93.1%, respectively, showing a non-significant difference in therapy efficacy between the two groups (P > 0.05). Safety analysis indicated that all the occurrence rates of skin and nail toxic reaction, body fluid retention, oral mucositis, allergic reaction (such as facial blushing, chest distress, palpitation, dyspnea. etc.), and grade III-IV leukopenia and neutropenia in the paclitaxel liposome group were significantly lower than that of the docetaxel group (all P < 0.05).
CONCLUSIONS
Compared with docetaxel, paclitaxel liposome has the same anti-tumor efficacy, but causes fewer and milder adverse reactions with a higher safety in the neoadjuvant chemotherapy for breast cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Docetaxel; Epirubicin; Female; Humans; Liposomes; Neoadjuvant Therapy; Neutropenia; Paclitaxel; Remission Induction; Taxoids
PubMed: 26463031
DOI: No ID Found