Pharmacokinetic study and clinical evaluation of a slow-release 5-fluorouracil implant in pancreatic cancer patients

Li, Jing Quan; Yang, Jing; Liang, Jianchao; Wang, Shi Liang

doi:10.1097/cad.0000000000000293

Cited by 7 publications

(8 citation statements)

References 11 publications

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“…Results indicate that the release of 5-FU and DEX from MSN-NH 2 -gel follow a controlled release pattern compared to their free drugs counterparts. This favorable release pattern of drugs from the nanoparticle system, for 5-FU in particular, has proven to be beneficial in prolonging the time of drug action and overcoming drug resistance as well as reducing any potential side effects [48,49]. Release profiles can further confirm the presence of an interaction between 5-FU MSN-NH 2 + DEX MSN-NH 2 .…”

Section: In Vitro Release Studiesmentioning

confidence: 84%

The Design of Anionic Surfactant-Based Amino-Functionalized Mesoporous Silica Nanoparticles and their Application in Transdermal Drug Delivery

et al. 2020

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Melanoma remains the most lethal form of skin cancer and most challenging to treat despite advances in the oncology field. Our work describes the utilization of nanotechnology to target melanoma locally in an attempt to provide an advanced and efficient quality of therapy. Amino-functionalized mesoporous silica nanoparticles (MSN-NH2) were developed in situ through the utilization of anionic surfactant and different volumes of 3-aminopropyltriethoxysilane (APTES) as a co-structure directing agent (CSDA). Prepared particles were characterized for their morphology, particles size, 5-flurouracol (5-FU) and dexamethasone (DEX) loading capacity and release, skin penetration, and cytotoxicity in vitro in HT-144 melanoma cells. Results of transmission electron microscopy (TEM) and nitrogen adsorption–desorption isotherm showed that using different volumes of APTES during the functionalization process had an impact on the internal and external morphology of the particles, as well as particle size. However, changing the volume of APTES did not affect the diameter of formed mesochannels, which was about 4 nm. MSN-NH2 showed a relatively high loading capacity of 5-FU (12.6 ± 5.5) and DEX (44.72 ± 4.21) when using drug: MSN-NH2 ratios of 5:1 for both drugs. The release profile showed that around 83% of 5-FU and 21% of DEX were released over 48 h in pH 7.4. The skin permeability study revealed that enhancement ratio of 5-Fu and DEX using MSN-NH2 were 4.67 and 5.68, respectively, relative to their free drugs counterparts. In addition, the accumulation of drugs in skin layers where melanoma cells usually reside were enhanced approximately 10 times with 5-FU and 5 times with DEX when delivering drugs using MSN-NH2 compared to control. MSN-NH2 alone was nontoxic to melanoma cells when incubated for 48 h in the range of 0 to 468 µg/mL. The combination of 5-FU MSN-NH2 and DEX MSN-NH2 showed significant increase in toxicity compared to their free dug counterparts and exhibited a synergetic effect as well as the ability to circumvent DEX induced 5-FU resistance in melanoma cells.

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Section: In Vitro Release Studiesmentioning

confidence: 84%

The Design of Anionic Surfactant-Based Amino-Functionalized Mesoporous Silica Nanoparticles and their Application in Transdermal Drug Delivery

et al. 2020

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“…This formulation enabled sustained release of fluorouracil within the abdominal cavity. The drug release time lasted longer than 30 days ( 27 ). The problem of the short half-life of fluorouracil was thus well resolved.…”

Section: Discussionmentioning

confidence: 99%

Intraperitoneal Chemotherapy Using Fluorouracil Implants Combined With Radical Resection and Postoperative Adjuvant Chemotherapy for Stage III Gastric Cancer: A Multi-Center, Randomized, Open-Label, Controlled Clinical Study

Zhang

et al. 2021

Front. Oncol.

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BackgroundReducing peritoneal recurrence after radical surgery is an important choice to improve the prognosis of patients with advanced gastric cancer. Intraoperative intraperitoneal chemotherapy has the potential to be a promising treatment strategy. In the present study, we conducted a multi-center, randomized, controlled clinical study to evaluate the efficacy and safety of intraoperative intraperitoneal chemotherapy using sustained-release fluorouracil implants plus radical gastrectomy and adjuvant chemotherapy for cTNM stage III gastric cancer.MethodsThe patients were randomized into intraperitoneal chemotherapy group (sustained-release fluorouracil implants administration after standard D2 radical gastrectomy, and followed by XELOX adjuvant chemotherapy) and control group (standard D2 radical gastrectomy, and followed by XELOX adjuvant chemotherapy). A total of 122 patients from three centers were enrolled from September 2015 to February 2017.ResultsOne hundred and two eligible patients completed the treatment course. The median follow-up time was 41.7 months (36.1–52.9 months). The 3-year progression-free survival rate and overall survival of patients in the intraperitoneal chemotherapy group were 43.9% and 49.1%, respectively, which were significantly better than those of the control group, 31.0% and 38.4%. In the intraperitoneal chemotherapy group, the number of cases with peritoneal recurrence was significantly less than that of the control group, 9 cases (17.3%) vs. 19 cases (44.2%). There were neither significant differences between the groups in the incidence of hematogenous metastasis, lymph node metastasis, nor local metastasis.ConclusionFor cTNM stage III gastric cancer, intraoperative sustained-release fluorouracil implants after radical resection combined with postoperative adjuvant chemotherapy, could significantly reduce the risk of peritoneal recurrence and prolong PFS.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier (NCT02269904).

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“…Four prospective studies performed intratumoral chemotherapy in 71 patients 73–76 . One RCT studied a chemotherapy capsule implant (5-fluorouracil) combined with systemic chemotherapy of gemcitabine versus systemic gemcitabine alone 74 .…”

Section: Resultsmentioning

confidence: 99%

“…One study analysed the intratumoral distribution of percutaneous injection by injecting 1–2 ml of radiopaque agent before injecting gemcitabine and cisplatin with fibrin glue 76 . Capsules incorporating 5-fluorouracil were implanted intraoperatively followed by fibrin gel to prevent pancreatic fistula 74 . Two studies, including 54 patients, reported 18 patients (33 per cent) with combined systemic chemotherapy and 36 (67 per cent) with chemoradiotherapy 73 , 74 .…”

Section: Resultsmentioning

confidence: 99%

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Intratumoral injection therapies for locally advanced pancreatic cancer: systematic review

Willink,

Jenniskens,

Klaassen

et al. 2023

BJS Open

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Introduction Pancreatic cancer has one of the worst prognoses of all cancers. Patients with locally advanced pancreatic cancer have a 12.7–20.2 per cent chance of receiving curative surgery after induction systemic chemotherapy. Intratumoral injection therapies have been studied as complementary treatment options for improved local tumour control. The aim of this systematic review was to provide an overview of intratumoral injection therapies, their safety, and oncological outcome in patients with locally advanced pancreatic cancer. Methods A literature search was conducted in PubMed, Embase and the Cochrane Library for articles written in English up to 28 November 2022. All study designs involving at least five patients with locally advanced pancreatic cancer who were treated with an intratumoral injection therapy were included. Critical appraisal of the included studies was performed using the Newcastle–Ottawa scale. Results After evaluation of the 1680 articles yielded by the systematic search, 52 studies treating 1843 patients were included. Included intratumoral injection treatment modalities comprised iodine-125 (125I) seed brachytherapy (32 studies, 1283 patients), phosphorus-32 (32P) microbrachytherapy (5 studies, 133 patients), palladium-103 (103Pd) seed brachytherapy (2 studies, 26 patients), immunotherapy (9 studies, 330 patients), and chemotherapy (4 studies, 71 patients). Overall survival ranged between 7.0 and 16.0 months for 125I, 5.2 and 15.5 months for 32P, 6.9 and 10.0 months for 103Pd, 5.8 and 13.8 months for immunotherapy, and 9.0 and 16.2 months for chemotherapy. Severe complication (greater than or equal to grade III complications using Clavien–Dindo classification) rates were 6.2 per cent for 125I, 49.2 per cent for 32P, 15 per cent for 103Pd, 57.9 per cent for immunotherapy, and 0 per cent for chemotherapy. Conclusion Five intratumoral injection therapies are described and an overview is reported. Some intratumoral injection therapies for patients with locally advanced pancreatic cancer seem safe, although 32P microbrachytherapy and immunotherapy require additional evidence. Currently available data are insufficient to provide firm conclusions regarding the added value to survival. The potential advantage of intratumoral injection therapies complementary to conventional care should be studied in well designed RCTs.

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Pharmacokinetic study and clinical evaluation of a slow-release 5-fluorouracil implant in pancreatic cancer patients

Cited by 7 publications

References 11 publications

The Design of Anionic Surfactant-Based Amino-Functionalized Mesoporous Silica Nanoparticles and their Application in Transdermal Drug Delivery

The Design of Anionic Surfactant-Based Amino-Functionalized Mesoporous Silica Nanoparticles and their Application in Transdermal Drug Delivery

Intraperitoneal Chemotherapy Using Fluorouracil Implants Combined With Radical Resection and Postoperative Adjuvant Chemotherapy for Stage III Gastric Cancer: A Multi-Center, Randomized, Open-Label, Controlled Clinical Study

Intratumoral injection therapies for locally advanced pancreatic cancer: systematic review

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