• Journal of Gastric Cancer
• /
• v.21 no.4
• /
• pp.418-425
• /
• 2021

Purpose: We designed a new regimen by combining intraperitoneal (IP) paclitaxel (PTX) with systemic S-1 plus oxaliplatin (SOX) for the treatment of advanced gastric cancer with peritoneal metastasis. This dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IP PTX administered weekly to patients. Materials and Methods: Eight cycles of IP PTX plus SOX regimen were administered to the patients. S-1 was administered orally twice daily at a dose of 80 mg/m²/day for 14 consecutive days, followed by 7 days of rest. Intravenous oxaliplatin was administered at a fixed dose of 100 mg/m² on day 1, while IP PTX was administered on days 1 and 8. The initial dose of IP PTX was 40 mg/m², and the dose escalation was set in units of 20 mg/m² up to 80 mg/m². Dose-limiting toxicities (DLTs) were defined as grade 3 non-hematologic toxicities, grade 4 leukopenia, grade 3 febrile neutropenia, and grade 3 thrombocytopenia. Results: Nine patients were included in the study. No DLTs were observed in any of the enrolled patients. Therefore, the MTD was not reached, and the RD of IP PTX was determined to be 80 mg/m². Four patients (44%) showed a decreased peritoneal cancer index score on second-look laparoscopic examination. Conclusions: The present study determined the dose for further clinical trials of IP PTX to be 80 mg/m², when combined with a systemic SOX regimen.

• BMB Reports
• /
• v.40 no.5
• /
• pp.731-739
• /
• 2007

The purpose of this study was to develop paclitaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles coated with cationic SM5-1 single-chain antibody (scFv) containing a polylysine (SMFv-polylys). SM5-1 scFv (SMFv) is derived from SM5-1 monoclonal antibody, which binds to a 230 kDa membrane protein specifically expressed on melanoma, hepatocellular carcinoma and breast cancer cells. SMFv-polylys was expressed in Escherichia coli and purified by cation-exchange chromatography. Purified SMFv-polylys was fixed to paclitaxel-loaded PLGA nanoparticles to form paclitaxel-loaded PLGA nanoparticles coated with SMFv-polylys (Ptx-NP-S). Ptx-NP-S was shown to retain the specific antigen-binding affinity of SMFv-polylys to SM5-1 binding protein-positive Ch-hep-3 cells. Finally, the cytotoxicity of Ptx-NP-S was evaluated by a non-radioactive cell proliferation assay. It was demonstrated that Ptx-NP-S had significantly enhanced in vitro cytotoxicity against Ch-hep-3 cells as compared with non-targeted paclitaxel-loaded PLGA nanoparticles. In conclusion, our results suggest that cationic SMFv-polylys has been successfully generated and may be used as targeted ligand for preparing cancer-targeted nanoparticles.

• Journal of Pharmaceutical Investigation
• /
• v.38 no.2
• /
• pp.127-134
• /
• 2008

Peroral administration is the most convenient one for the administration of pharmaceutically active compounds. Most of poorly water-soluble drugs administered via the oral route, however, remain poorly available due to their precipitation in the gastrointestinal (GI) tract and low permeability through intestinal mucosa. In this study, one of drug delivery carriers, lipid nanoparticles (LNPs) were designed in order to reduce side effects and improve solubility and stability in GI tract of the poorly water soluble drugs. However, plain LNPs are generally unstable in the GI tract and susceptible to the action of acids, bile salts and enzymes. Accordingly, the surface of LNPs was modified with polyethylene glycol (PEG) for the purpose of improving solubility and GI stability of paclitaxel (PTX) in vitro. PEG-modified LNPs containing PTX was prepared by spontaneous emulsification and solvent evaporation (SESE) method and characterized for mean particle diameter, entrapping efficiency, zeta potential value and in vitro GI stability. Mean particle diameter and zeta potential value of PEG-modified LNP containing PTX showed approximately 86.9 nm and -22.9 mV, respectively. PTX entrapping efficiency was about 70.5% determined by UV/VIS spectrophotometer. Futhermore, change of particle diameter of PTX-loaded PEG-LNPs in simulated GI fluids and bile fluid was evaluated as a criteria of GI stability. Particle diameter of PTX-loaded PEG-LNPs were preserved under 200 nm for 6 hrs in simulated GI fluids and bile fluid at $37^{\circ}C$ when DSPE-mPEG2000 was added to formulation of LNPs above 4 mole ratio. As a result, PEG-modified LNPs improved stability of plain LNPs that would aggregate in simulated GI fluids and bile solution. These results indicate that LNPs modified with biocompatible and nontoxic polymer such as PEG might be useful for enhancement of GI stability of poorly water-soluble drugs and they might affect PTX absorption affirmatively in gastrointestinal mucosa.

• Bulletin of the Korean Chemical Society
• /
• v.35 no.5
• /
• pp.1333-1336
• /
• 2014

Expanded polytetrafluoroethylene (ePTFE) grafts have been used as vascular access for many patients suffering from end stage renal disease. However, the vascular graft can cause significant clinical problems such as stenosis or thrombosis. For this reason, many studies have been performed to make drug eluting graft, but initial burst is major problem in almost drug eluting systems. Therefore we used biodegradable polymer to reduce initial burst and make sustained drug delivery. The ePTFE grafts were dipped into a paclitaxel-dissolved solution and then PLGA-dissolved solution was passed through the lumen of ePTFE. We analyzed whether the dose of paclitaxel is enough and the loading amount of PLGA on ePTFE graft increases according to the coating solution's concentration. Scanning electron microscope (SEM) images of various concentration of PLGA showed that the porous surface of graft was more packed with PLGA by tetrahydrofuran solution dissolved PLGA. In addition, in vitro release profiles of Ptx-PLGA graft demonstrated that early burst was gradually decreased as increasing the concentration of PLGA. These results suggest that PLGA coating of Ptx loaded graft can retard drug release, it is useful tool to control drug release of medical devices.

• Polymer(Korea)
• /
• v.38 no.1
• /
• pp.93-97
• /
• 2014

Biodegradable drug-eluting stent has dual functions of supporting the lumen and treating internal tumor preventing the restenosis by releasing drug. In this study, the polycaprolactone (PCL) based three dimensional (3D) mesh loaded with paclitaxel (PTX) was presented by rapid prototyping (RP) technique of solid freeform fabrication (SFF) for biodegradable drug-eluting stent application. PCL has many advantageous properties such as good biocompatibility, good mechanical properties, and good drug permeability. PTX is widely used in the cancer treatment by inhibiting tumor cell proliferation. Analytical methods of HPLC and NMR were used for simultaneous quantification of PTX. Scanning electron microscopy (SEM) was performed to observe the architecture and morphologies of 3D mesh. The cytotoxicity assay results indicated released PTX's biological activity. This study provided that PCL based 3D mesh loaded with PTX by RP technique has great potential for biodegradable drug-eluting stent application.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.228.1-228.1
• /
• 2002

Hypoxia in solid tumors is known to contribute to intrinsic chemoresistance. Tirapazamine(TPZ). a hypoxia-selective cytotoxin. showed synergism with radiation or cytotoxic agents. Paclitaxel(PTX) is a highly active anti-cancer agent against Non small cell lung cancer(NSCLC), however. due to poor penetration into central hypoxic region of tumor tissue. combination with TPZ has been suggested to enhance its efficacy. (omitted)

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.13
• /
• pp.5493-5498
• /
• 2014

Objective: To compare the efficacy of taxane-based regimens in the first line setting retrospectively in Chinese patients with recurrent and/or metastatic esophageal cancer. Methods: We analyzed 102 recurrent and/or metastatic esophageal cancer patients who received taxanes-based regimens in a first-line setting from January 2009 to December 2013. Sixteen (15.7%) patients were administered Nab-PTX based chemotherapy and 86 patients (84.3%) received paclitaxel (PTX) or docetaxel (DTX) based chemotherapy. Patients in the PTX/DTX group could be further divided into TP (71 patients) and TPF (15 patients) groups. Results: The objective response rate (ORR) of all patients was 20.6%, and the disease control rate (DCR) was 67.6%. The median overall survival (OS) was 10.5 months (95% CI 10.1-16.4) and the median progression-free survival (PFS) was 6.04 months (95% CI 5.09-7.91). The DCR was higher in the TPF group than the TP group (93.3% vs. 59.1%; p = 0.015 ). There were no significant differences in ORR, OS, and PFS among Nab-PTX, TPF and TP groups. Conclusions: The three regimens of Nab-PTX based, TP and TPF proved active in a first line setting of Chinese patients with recurrent and/or metastatic esophageal cancer, and should thus be regarded as alternative treatments.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.11
• /
• pp.5587-5591
• /
• 2012

Objective: This study was performed to evaluated the efficacy and safety of continuous infusional paclitaxel and 5-Fu as first-line chemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Methods: A total of 22 patients with advanced esophageal squamous cell cancer with no indications for surgery and radiation therapy, or recurrent patients were enrolled from October 2008 to November 2010. All were treated with PTX 20 $mg/m^2$ was administered through a 16 hours continuous intravenous infusion on days 1 to 3, 8 and 9. DDP 3.75 $mg/m^2$ was given on days 1 to 4 and 8 to 11, continuous infusional 5-FU over 24-hours on days 1 to 5 and 8 to 12 at a dose of 375 $mg/m^2$, and folacin 60 mg orally synchronized with 5-Fu. The treatment was repeated every 21 days for at least two cycles. Results: 22 cases of all enrolled patients could be evaluated for the effect of treatment: 2 cases were CR, 9 cases PR, 5 cases SD and 2 cases PD, giving an overall response rate of 68.2%(15/22). The median time to progression was 7.0 months. The adverse reactions related to chemotherapy were tolerable; the most common toxic effects were marrow depression, alopecia, and fatigue. Conclusion: Low-dose continuous infusional PTX over 16-hours and 5-fu over 24-hours is a promising regimen with good tolerability in treating patients with advanced esophageal squamous cell cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.12
• /
• pp.7561-7568
• /
• 2013

Galectin-3 (Gal-3) is a carbohydrate-binding protein which is thought to be involved in cancer progression but its contribution to epithelial ovarian cancer (EOC) remains unclear. The present study sought to determine the role of Gal-3 in chemoresistance of the human SKOV-3 ovarian cancer cell line to paclitaxel (PTX) using recombinant human Gal-3 (rhGal-3) and PectaSol-C modified citrus pectin (Pect-MCP) as a specific Gal-3 competitive inhibitor. Our results showed 41% increased cell proliferation, 36% decreased caspase-3 activity and 33.6% increased substrate-dependent adhesion in the presence of rhGal-3 compared to the control case (p<0.001). Treatment of cells with a non-effective dose of PTX (100nM) and 0.1% Pect-MCP in combination revealed synergistic cytotoxic effects with 75% reduced cell viability and subsequent 3.9-fold increase in caspase-3 activity. Moreover, there was 39% decrease in substrate-dependent adhesion compared to control (p<0.001). These results suggest that inhibition of Gal-3 could be a useful therapeutic tool for combination therapy of ovarian cancer.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.227.2-228
• /
• 2002

ZD1839 is a new anticancer agent which selectively inhibits EGFR tyrosine kinase. Oxaliplatin (LOHP), 5-FU (FU), and paclitaxel (PTX) have shown to be highly active against the gastric carcinomas. and ZD1839 is considered as a good candidate for the treatment of gastric cancers when combined with cytotoxic agents. In this study, we evaluated the antitumor effects of these agents in SNU-l human gastric cancer cells either alone or when given as a doublet. (omitted)