-
Clinical Therapeutics Nov 2017Pancreatic cancer has a dismal prognosis due to the early development of systemic metastatic disease. Chemotherapeutic agents are the only systemic therapy that offers... (Review)
Review
PURPOSE
Pancreatic cancer has a dismal prognosis due to the early development of systemic metastatic disease. Chemotherapeutic agents are the only systemic therapy that offers patients meaningful benefit.
METHODS
This study reviewed the literature for recently published Phase III clinical trials whose results have guided the current standards of chemotherapy for pancreatic cancer.
FINDINGS
Although combination chemotherapy regimens are shown to be superior to gemcitabine monotherapy for both metastatic pancreatic cancer and adjuvant chemotherapy after surgical resection, it should be recognized that all combination chemotherapy regimens offer only limited benefits. In addition, there is a paucity of clinical trials that directly compare the various combination chemotherapy regimens.
IMPLICATIONS
With the advancement of systemic cancer treatment beyond chemotherapy, it is important to devote more investigation into better understanding the biology of these chemotherapy regimens, such that we combine them with targeted therapeutics and immunotherapeutics in a rational and scientific manner. For the current treatment of pancreatic cancer, the available chemotherapy regimens have shown modest but statistically significant improvements in survival. However, it is important to avoid cross-comparisons of trials and choose regimens based on patient characteristics and the side-effect profiles of the regimen.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Humans; Pancreatic Neoplasms; Gemcitabine
PubMed: 28939405
DOI: 10.1016/j.clinthera.2017.08.015 -
Cancer Medicine Mar 2023This single-center retrospective clinical study aimed to evaluate the efficacy and feasibility of chemoradiotherapy with paclitaxel liposome plus cisplatin for locally...
PURPOSE
This single-center retrospective clinical study aimed to evaluate the efficacy and feasibility of chemoradiotherapy with paclitaxel liposome plus cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC).
METHODS
Patients with locally advanced ESCC treated with paclitaxel-liposome-based chemoradiotherapy between 2016 and 2019 were retrospectively analyzed. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis.
RESULTS
Thirty-nine patients with locally advanced ESCC were included in this study. The median follow-up time was 31.5 months. The median OS time was 38.3 (95% confidence interval [CI]: 32.1-45.1) months, and the 1-, 2-, and 3-year OS rates were 84.6%, 64.1%, and 56.2%, respectively. The median PFS time was 32.1 (95% CI: 25.4-39.0) months, and the 1-, 2-, and 3-year PFS rates were 71.8%, 43.6%, and 43.6%, respectively. The most common Grade IV toxicity was neutropenia (30.8%) followed by lymphopenia (20.5%). There were no cases of Grade III/IV radiation pneumonia, and four patients (10.3%) had Grade III/IV esophagitis.
CONCLUSION
Chemoradiotherapy using paclitaxel liposome and cisplatin is a well-tolerated and effective treatment regimen for locally advanced ESCC.
Topics: Humans; Esophageal Squamous Cell Carcinoma; Cisplatin; Esophageal Neoplasms; Retrospective Studies; Liposomes; Carcinoma, Squamous Cell; Disease-Free Survival; Paclitaxel; Chemoradiotherapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37012831
DOI: 10.1002/cam4.5416 -
International Journal of Nanomedicine 2018In the present study, the tumor-specific, pH-responsive peptide HK(R)-modified, theranostic liposome-containing paclitaxel (PTX) and superparamagnetic iron oxide...
BACKGROUND
In the present study, the tumor-specific, pH-responsive peptide HK(R)-modified, theranostic liposome-containing paclitaxel (PTX) and superparamagnetic iron oxide nanoparticles (SPIO NPs), PTX/SPIO-SSL-HK(R), was prepared by using HK(R) as the targeting ligand, SPIO NPs as the magnetic resonance imaging (MRI) agent, PTX as antitumor drug.
METHODS
The PTX/SPIO-SSL-HK(R) was prepared by a thin film hydration method. The characteristics of PTX/SPIO-SSL-HK(R) were evaluated. The targeting effect, MRI, and antitumor activity of PTX/SPIO-SSL-HK(R) were investigated detail in vitro and in vivo in human breast carcinoma MDA-MB-231 cell models.
RESULTS
Our results of in vitro flow cytometry, in vivo imaging, and in vivo MR imaging confirmed the pH-responsive characteristic of HK(R) in MDA-MB-231 cell line in vitro and in vivo. The results of in vivo MRI and in vivo antitumor activity confirmed the theranostic effect of PTX/SPIO-SSL-HK(R) in MDA-MB-231 tumor-bearing model.
CONCLUSION
Considering all our in vitro and in vivo results, we conclude that we developed targeting modified theranostic liposome which could achieve both role of antitumor and MRI.
Topics: Animals; Antineoplastic Agents; Cell Death; Cell Line, Tumor; Drug Liberation; Female; Ferric Compounds; Flow Cytometry; Humans; Hydrogen-Ion Concentration; Liposomes; Magnetic Resonance Imaging; Magnetite Nanoparticles; Mice, Inbred BALB C; Mice, Nude; Neoplasms; Paclitaxel; Peptides; Theranostic Nanomedicine; Tissue Distribution
PubMed: 29559778
DOI: 10.2147/IJN.S157082 -
Journal of Pharmacy & Pharmaceutical... 2006An important step in the development of liposome-based formulations is estimating the free drug concentration in the aqueous solution surrounding liposomes. This...
PURPOSE
An important step in the development of liposome-based formulations is estimating the free drug concentration in the aqueous solution surrounding liposomes. This research presents a new method for determination of free concentrations, based on membrane-protected solid-phase microextraction (SPME).
METHODS
For effective direct extraction of low molecular weight compounds from complex liquid samples, a hollow membrane was used to form a concentric sheath around a coated SPME fiber. The membrane blocked the access of large particles, like liposomes, to the coating surface, while target analytes with low molecular weight diffused through the membrane and reached the extraction phase. Quantification was conveniently performed by reversed-phase liquid chromatography coupled to electrospray ionization mass spectrometry.
RESULTS
The carbowax/templated resin SPME fiber was determined to be the most suitable for these assays, providing enough sensitivity when an extraction time of one hour was used. The free concentration of paclitaxel was found to be 0.36 microg/mL, significantly below the solubility limit of paclitaxel in water.
CONCLUSION
The method was successfully applied for determining free paclitaxel in liposome formulations based on dioleyl-trimethyl-ammonium-propane, with good linearity over the range of concentrations of interest. The method was faster and more practical than equilibrium dialysis, as the SPME approach provided preconcentration and convenient delivery to the analytical system.
Topics: Antineoplastic Agents; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Liposomes; Mass Spectrometry; Paclitaxel; Solubility
PubMed: 16959192
DOI: No ID Found -
Journal of Geriatric Oncology Apr 2023Pancreatic cancer is the fourth leading cause of cancer-related death in the US with an increasing incidence in older adults (OA) over age 70. There are currently no... (Randomized Controlled Trial)
Randomized Controlled Trial
The GIANT trial (ECOG-ACRIN EA2186) methods paper: A randomized phase II study of gemcitabine and nab-paclitaxel compared with 5-fluorouracil, leucovorin, and liposomal irinotecan in older patients with treatment-naïve metastatic pancreatic cancer - defining a new treatment option for older...
INTRODUCTION
Pancreatic cancer is the fourth leading cause of cancer-related death in the US with an increasing incidence in older adults (OA) over age 70. There are currently no treatment guidelines for OA with metastatic pancreatic cancer (mPCA) and selecting a chemotherapy regimen for these patients is subjective, based largely on chronologic age and performance status (PS). Geriatric screening tools provide a more objective and accurate evaluation of a patient's overall health but have not yet been validated in patient selection for mPCA treatment. This study aims to elucidate the optimal chemotherapy treatment of vulnerable OA with mPCA and understand the geriatric factors that affect outcomes in this population.
METHODS/DESIGN
The GIANT (ECOG-ACRIN EA2186) study is multicenter, randomized phase II trial enrolling patients over age 70 with newly diagnosed mPCA. This study utilizes a screening geriatric assessment (GA) which characterizes patients as fit, vulnerable, or frail. Patients with mild abnormalities in functional status and/or cognition, moderate comorbidities, or over age 80 are considered vulnerable. Enrolled patients are randomized to one of two dose-reduced treatment regimens (gemcitabine/nab-paclitaxel every other week, or dose-reduced 5-fluoruracil (5FU)/ liposomal irinotecan (nal-IRI) every other week). GA and quality of life (QoL) evaluations are completed prior to treatment initiation and at each disease evaluation. Overall survival (OS) is the primary endpoint, with secondary endpoints including progression free survival (PFS) and objective response rate (ORR). Enrolled patients will be stratified by age (70-74 vs ≥75) and ECOG PS (0-1 vs 2). Additional endpoints of interest for OA include evaluation of risk factors identified through GA, QoL evaluation, and toxicities of interest for older adults. Correlative studies include assessment of pro-inflammatory biomarkers of aging in the blood (IL-6, CRP) and imaging evaluation of sarcopenia as predictors of treatment tolerance.
DISCUSSION
The GIANT study is the first randomized, prospective national trial evaluating vulnerable OA with mPCA aimed at developing a tailored treatment approach for this patient population. This trial has the potential to establish a new way of objectively selecting vulnerable OA with mPCA for modified treatment and to establish a new standard of care in this growing patient population.
TRIAL REGISTRATION
This trial is registered with ClinicalTrial.gov Identifier NCT04233866.
Topics: Humans; Aged; Aged, 80 and over; Irinotecan; Gemcitabine; Fluorouracil; Leucovorin; Quality of Life; Prospective Studies; Pancreatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36963200
DOI: 10.1016/j.jgo.2023.101474 -
Lakartidningen Jul 2017Nanoparticles for cancer therapy Nanoparticles carry a big promise in oncology, for diagnosis/imaging, therapy, or both (theragnostics). As common in medical history,...
Nanoparticles for cancer therapy Nanoparticles carry a big promise in oncology, for diagnosis/imaging, therapy, or both (theragnostics). As common in medical history, there is a huge gap between the exciting experimental possibilities and data and clinical studies making use of it. Of the cell-containing nanoparticles, only one formulation using gene-directed enzyme prodrug therapy (GDEPT) with CYP2B1 and ifosfamide was used in early clinical studies. Of the cell-free nanoparticles, some drug-releasing (doxorubicin) ones are in clinical use for trans-arterial chemo-embolization (TACE) in liver tumors and metastasis. Using liposomes, both paclitaxel and irinotecan have been used in pancreatic cancer as the model indication. Nanoparticle-albumin-bound paclitaxel (NAB-paclitaxel) has also been developed and is now registered as a drug for first-line therapy of pancreatic cancer, as is the liposomal irinotecan. The novel nanoparticle formulations carry a big promise for even better performance, both in diagnosis and therapy; however, few of these has entered the clinic as of today.
Topics: Antineoplastic Agents; Humans; Liposomes; Nanocapsules; Nanomedicine; Nanoparticles; Neoplasms; Pancreatic Neoplasms
PubMed: 28675414
DOI: No ID Found -
Oncotarget Aug 2017Ovarian neoplasm is a kind of high risky cancer among female. This paper assessed the efficacy and safety of twelve therapies and figured out the superior... (Review)
Review
BACKGROUND
Ovarian neoplasm is a kind of high risky cancer among female. This paper assessed the efficacy and safety of twelve therapies and figured out the superior chemotherapeutic drug for ovarian cancer through network meta-analysis (NMA).
METHOD
Eligible randomized controlled trials (RCTs) were retrieved from electronic databases. Primary outcomes concerning efficacy, overall survival (OS) and progression-free survival (PFS), were presented as hazard ratio (HR) and the associated 95% credible interval(), while outcomes concerning safety were assessed by odds ratio (OR) and the corresponding 95% . Surface under the cumulative ranking curve (SUCRA) was calculated under each survival and safety outcome in order to show the rankings of tested therapies.
RESULT
Electronic databases such as PubMed and Embase were searched to finally obtain 19 eligible studies of 16290 patients. In accordance of primary outcomes, when it came to 3-y PFS, paclitaxel/epirubicin/carboplatin (Pa/E/Ca) and pegylated liposomal doxorubicin/ paclitaxel/ carboplatin (PLD/Pa/Ca) were preferred compared to carboplatin (Ca) (HR= 0.80, 95% = 0.67-0.96; HR= 0.83, 95% = 0.69-0.99). According to 5y-PFS, Pa/E/Ca was notably better than Ca (HR= 0.80, 95% = 0.65-0.99). As to adverse effects, Ca was superior to Pa/E/Ca in neuropathy (HR=0.05, 95% =0.02-0.19). Pa/E/Ca showed high rankings in 3y-PFS (SUCRA=0.749), 5y-OS (SUCRA=0.738) and 5y-PFS (SUCRA=0.798) while (PLD/Pa/Ca) in 3y-OS (SUCRA=0.737), 5y-OS (SUCRA=0.687) and 5y-PFS (SUCRA=0.712). Besides, Pa/E/Ca ranked the third with a SUCRA of 0.661 in neutropenia.
CONCLUSION
PLD/Pa/Ca, PLD/Ca and Pa/E/Ca are highly recommended as potential therapeutically choices for patients with ovarian cancer. But considering the lack of safety data for PLD/Pa/Ca, this intervention should be taken with caution.
PubMed: 28938689
DOI: 10.18632/oncotarget.16729 -
Journal of Materials Science. Materials... Dec 2021In this study, paclitaxel (PTX)-loaded pH-responsive niosomes modified with ergosterol were developed. This new formulation was characterized in terms of size,...
In this study, paclitaxel (PTX)-loaded pH-responsive niosomes modified with ergosterol were developed. This new formulation was characterized in terms of size, morphology, encapsulation efficiency (EE), and in vitro release at pH 5.2 and 7.4. The in vitro efficacy of free PTX and niosome/PTX was assessed using MCF7, Hela, and HUVEC cell lines. In order to evaluate the in vivo efficacy of niosomal PTX in rats as compared to free PTX, the animals were intraperitoneally administered with 2.5 mg/kg and 5 mg/kg niosomal PTX for two weeks. Results showed that the pH-responsive niosomes had a nanometric size, spherical morphology, 77% EE, and pH-responsive release in pH 5.2 and 7.4. Compared with free PTX, we found markedly lower IC50s when cancer cells were treated for 48 h with niosomal PTX, which also showed high efficacy against human cancers derived from cervix and breast tumors. Moreover, niosomal PTX induced evident morphological changes in these cell lines. In vivo administration of free PTX at the dose of 2.5 mg/kg significantly increased serum biochemical parameters and liver lipid peroxidation in rats compared to the control rats. The situation was different when niosomal PTX was administered to the rats: the 5 mg/kg dosage of niosomal PTX significantly increased serum biochemical parameters, but the group treated with the 2.5 mg/kg dose of niosomal PTX showed fewer toxic effects than the group treated with free PTX at the same dosage. Overall, our results provide proof of concept for encapsulating PTX in niosomal formulation to enhance its therapeutic efficacy.
Topics: Animals; Antineoplastic Agents; Drug Liberation; HeLa Cells; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen-Ion Concentration; Lipid Peroxidation; Liposomes; MCF-7 Cells; Male; Paclitaxel; Rats; Rats, Sprague-Dawley
PubMed: 34862910
DOI: 10.1007/s10856-021-06623-6 -
Molecules (Basel, Switzerland) Nov 2022A series of novel paclitaxel derivatives modified by boronic acid according to the characteristics of the interaction between RB(OH)2 and different strapping agents of...
A series of novel paclitaxel derivatives modified by boronic acid according to the characteristics of the interaction between RB(OH)2 and different strapping agents of intraliposomal aqueous phase were designed and synthesized, which were then used to develop remote poorly water-soluble drugs loading into liposomes. Meanwhile, we screened nineteen paclitaxel boronic acid derivatives for their cytotoxic activities against three cancer cell lines (A549, HCT-116 and 4T1) and one normal cell line (LO2), and performed liposome formulation screening of active compounds. Among all the compounds, the liposome of 4d, with excellent drug-encapsulated efficiency (>95% for drug-to-lipid ratio of 0.1 w/w), was the most stable. Furthermore, the liposomes of compound 4d (8 mg/kg, 4 times) and higher dose of compound 4d (24 mg/kg, 4 times) showed better therapeutic effect than paclitaxel (8 mg/kg, 4 times) in the 4T1 tumor model in vivo, and the rates of tumor inhibition were 74.3%, 81.9% and 58.5%, respectively. This study provided a reasonable design strategy for the insoluble drugs to improve their drug loading into liposomes and anti-tumor effect in vivo.
Topics: Liposomes; Paclitaxel; Drug Stability; Boronic Acids
PubMed: 36432067
DOI: 10.3390/molecules27227967 -
Molecules (Basel, Switzerland) Apr 2022The problems with anticancer therapy are resistance and toxicity. From 3000 Cisplatin derivatives tested as antitumor agents, most of them have been rejected, due to... (Review)
Review
The problems with anticancer therapy are resistance and toxicity. From 3000 Cisplatin derivatives tested as antitumor agents, most of them have been rejected, due to toxicity. The aim of current study is the comparison of therapeutic combinations of the currently applied in clinical practice: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, Heptaplatin, and Satraplatin. The literature data show that the strategies for the development of platinum anticancer agents and bypassing of resistance to Cisplatin derivatives and their toxicity are: combination therapy, Pt IV prodrugs, the targeted nanocarriers. The very important strategy for the improvement of the antitumor effect against different cancers is synergistic combination of Cisplatin derivatives with: (1) anticancer agents-Fluorouracil, Gemcitabine, Cytarabine, Fludarabine, Pemetrexed, Ifosfamide, Irinotecan, Topotecan, Etoposide, Amrubicin, Doxorubicin, Epirubicin, Vinorelbine, Docetaxel, Paclitaxel, Nab-Paclitaxel; (2) modulators of resistant mechanisms; (3) signaling protein inhibitors-Erlotinib; Bortezomib; Everolimus; (4) and immunotherapeutic drugs-Atezolizumab, Avelumab, Bevacizumab, Cemiplimab, Cetuximab, Durvalumab, Erlotinib, Imatinib, Necitumumab, Nimotuzumab, Nivolumab, Onartuzumab, Panitumumab, Pembrolizumab, Rilotumumab, Trastuzumab, Tremelimumab, and Sintilimab. An important approach for overcoming the drug resistance and reduction of toxicity of Cisplatin derivatives is the application of nanocarriers (polymers and liposomes), which provide improved targeted delivery, increased intracellular penetration, selective accumulation in tumor tissue, and enhanced therapeutic efficacy. The advantages of combination therapy are maximum removal of tumor cells in different phases; prevention of resistance; inhibition of the adaptation of tumor cells and their mutations; and reduction of toxicity.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Erlotinib Hydrochloride; Humans; Neoplasms
PubMed: 35458666
DOI: 10.3390/molecules27082466