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Indian Journal of Cancer 2015Applications of nanotechnology in medicine and cancer are becoming increasingly popular. Common nanomaterials and devices applicable in cancer medicine are classifiable... (Review)
Review
Applications of nanotechnology in medicine and cancer are becoming increasingly popular. Common nanomaterials and devices applicable in cancer medicine are classifiable as liposomes, polymeric-micelles, dendrimers, nano-cantilevers, carbon nanotubes, quantum dots, magnetic-nanoparticles, gold nanoparticles (AuNPs) and certain miscellaneous nanoparticles. Here, we present review of the structure, function and utilities of the various approved, under trial and pretrial nanodevices applicable in the cancer care and medicine. The liposomes are phospholipid-vesicles made use in carrying drugs to the target site minimizing the bio-distribution toxicity and a number of such theranostics have been approved for clinical practice. Newly worked out liposomes and polymeric micelles are under the trail phases for nano-therapeutic utility. A multifunctional dendrimer conjugate with imaging, targeting and drug molecules of paclitaxel has been recently synthesized for cancer theranostic applications. Nano-cantilever based assays are likely going to replace the conventions methods of chemical pathological investigations. Carbon nanotubes are emerging for utility in regenerative and cancer medicine. Quantum dots hold great promise for the micro-metastasis and intra-operative tumor imaging. Important applications of magnetic nanoparticles are in the cardiac stents, photodynamic therapy and liver metastasis imaging. The AuNPs have been employed for cell imaging, computed tomography and cancer therapy. Besides these categories, miscellaneous other nanoparticles are being discovered for utility in the cancer diagnosis and disease management. However, the use of nanoparticles should be cautious since the toxic effects of nanoparticles are not well-known. The use of nanoparticles in the clinical practice and their toxicity profile require further extensive research.
Topics: Dendrimers; Drug Delivery Systems; Humans; Nanoparticles; Nanotechnology; Nanotubes, Carbon; Neoplasms
PubMed: 26837958
DOI: 10.4103/0019-509X.175591 -
Geburtshilfe Und Frauenheilkunde Dec 2020Epithelial ovarian cancer is the most common cause of death from gynecological tumors. Most patients with advanced ovarian cancer develop recurrence after concluding...
Epithelial ovarian cancer is the most common cause of death from gynecological tumors. Most patients with advanced ovarian cancer develop recurrence after concluding first-line therapy, making further lines of therapy necessary. The choice of therapy depends on various criteria such as tumor biology, the patient's general condition (ECOG), toxicity, previous chemotherapy, and response to chemotherapy. The platinum-free or treatment-free interval determines the potential response to repeat platinum-based therapy. If patients have late recurrence, i.e. > 6 months after the end of the last platinum-based therapy (i.e., they were previously platinum-sensitive), then they are usually considered suitable for another round of a platinum-based combination therapy. Patients who are not considered suitable for platinum-based chemotherapy are treated with a platinum-free regimen such as weekly paclitaxel, pegylated liposomal doxorubicin (PLD), gemcitabine, or topotecan. Treatment for the patient subgroup which is considered suitable for platinum-based therapy but cannot receive carboplatin due to uncontrollable hypersensitivity reactions may consist of trabectedin and PLD. While the use of surgery to treat recurrence has long been a controversial issue, new findings from the DESKTOP III study of the AGO working group have drawn attention to this issue again, particularly for patients with a platinum-free interval of > 6 months and a positive AGO score. Clinical studies have also shown the efficacy of angiogenesis inhibitors such as bevacizumab and the PARP inhibitors olaparib, niraparib and rucaparib. These drugs have substantially changed current treatment practice and expanded the range of available therapies. It is important to differentiate between purely maintenance therapy after completing CTX, continuous maintenance therapy during CTX, and the therapeutic use of these substances. The PARP inhibitors niraparib, olaparib and rucaparib have already been approved for use by the FDA and the EMA. The presence of a BRCA mutation is a predictive factor for a better response to PARP inhibitors.
PubMed: 33293727
DOI: 10.1055/a-1128-0280 -
Frontiers in Pharmacology 2017Natural resources continue to be an invaluable source of new, novel chemical entities of therapeutic utility due to the vast structural diversity observed in them. The... (Review)
Review
Natural resources continue to be an invaluable source of new, novel chemical entities of therapeutic utility due to the vast structural diversity observed in them. The quest for new and better drugs has witnessed an upsurge in exploring and harnessing nature especially for discovery of antimicrobial, antidiabetic, and anticancer agents. Nature has historically provide us with potent anticancer agents which include vinca alkaloids [vincristine (VCR), vinblastine, vindesine, vinorelbine], taxanes [paclitaxel (PTX), docetaxel], podophyllotoxin and its derivatives [etoposide (ETP), teniposide], camptothecin (CPT) and its derivatives (topotecan, irinotecan), anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin), and others. In fact, half of all the anti-cancer drugs approved internationally are either natural products or their derivatives and were developed on the basis of knowledge gained from small molecules or macromolecules that exist in nature. Three new anti-cancer drugs introduced in 2007, viz. trabectedin, epothilone derivative ixabepilone, and temsirolimus were obtained from microbial sources. Selective drug targeting is the need of the current therapeutic regimens for increased activity on cancer cells and reduced toxicity to normal cells. Nanotechnology driven modified drugs and drug delivery systems are being developed and introduced in the market for better cancer treatment and management with good results. The use of nanoparticulate drug carriers can resolve many challenges in drug delivery to the cancer cells that includes: improving drug solubility and stability, extending drug half-lives in the blood, reducing adverse effects in non-target organs, and concentrating drugs at the disease site. This review discusses the scientific ventures and explorations involving application of nanotechnology to some selected plant derived molecules. It presents a comprehensive review of formulation strategies of phytoconstituents in development of novel delivery systems like liposomes, functionalized nanoparticles (NPs), application of polymer conjugates, as illustrated in the graphical abstract along with their advantages over conventional drug delivery systems supported by enhanced biological activity in and anticancer assays.
PubMed: 29479316
DOI: 10.3389/fphar.2017.01002 -
Pharmaceutics Dec 2022Liposomes can increase plasma half-life, enhance targeting, and diminish the side-effects of loaded drugs. On the downside, physical and chemical instabilities of...
UNLABELLED
Liposomes can increase plasma half-life, enhance targeting, and diminish the side-effects of loaded drugs. On the downside, physical and chemical instabilities of dispersions often result in a reduced lifespan, which limits their availability on the market. Solid formulations obtained by freeze-drying can immobilize vesicles and provide extended shelf life. For both processes, the choice of excipients and process parameters are crucial to protect the carrier layers against tension caused by freezing and/or dehydration. The aim of this work is to evaluate the influence of freezing and drying parameters, besides excipient choice, to obtain solid long-circulating and fusogenic liposomes (LCFL-PTX/DXR) co-encapsulating paclitaxel (PTX) and doxorubicin (DXR) at a synergistic ratio (1:10).
METHODS
LCFL-PTX/DXR was evaluated by freeze-drying microscopy (glass transition, Tg'), differential scanning calorimetry (collapse temperature, Tc), freeze-thawing and freeze-drying processes. Freeze-dried samples were evaluated by thermogravimetry (residual moisture) and the resuspended liposomes were characterized in terms of size, polydispersity index (PI), zeta potential (ZP), and drug content. Liposomes morphology was evaluated by cryomicroscopy.
RESULTS
Trehalose protected PTX cargo upon freeze-thawing and more than 80% of the original DXR retention. The formulations with trehalose resulted in a cake with 5-7% of moisture content (200-240 nm); 44-60% of PTX retention, and 25-35% of DXR retention, with the variations caused by cryoprotector concentration and process changes.
CONCLUSIONS
Trehalose protected liposome integrity, maintaining PTX retention and most of DXR upon freeze-thawing. Freeze-drying reduced the retention of both drugs inside all liposomes, whereas formulation with trehalose presented minor losses. Therefore, this frozen formulation is an alternative product option, with no need for manipulation before use.
PubMed: 36678715
DOI: 10.3390/pharmaceutics15010086 -
European Review For Medical and... Dec 2017Kaposi's Sarcoma (KS) is a multicentric angioproliferative cancer of endothelial cells (ECs) caused by Human Herpesvirus 8 (HHV8) characterized by clinical heterogeneity... (Review)
Review
Kaposi's Sarcoma (KS) is a multicentric angioproliferative cancer of endothelial cells (ECs) caused by Human Herpesvirus 8 (HHV8) characterized by clinical heterogeneity depending on the host immune conditions. Despite its incidence has dramatically decreased in developed countries after the introduction of Highly Active Antiretroviral Therapy (HAART), KS remains the most frequent tumor in HIV-infected patients worldwide. Clinical presentation varies from an indolent slowly progressive behavior, generally limited to the skin, to an aggressive and rapidly progressing disease. In more than 50% of cases, the skin lesions are often associated with a more or less important visceral involvement, particularly to the oral cavity and the gastrointestinal tract that are involved in 35% and 40% of cases respectively. A large number of treatments can be used both as local and as systemic therapy. Particularly, HAART represents the first treatment in patients with moderate lesions limited to skin, and it can be sufficient to reduce significantly the size of lesions and, often, the complete disappear in 35% of cases after 3-9 months of treatment. In case of a rapidly progressive disease with extensive cutaneous and/or visceral involvement systemic drugs are used such as the liposomal anthracyclines pegylated liposomal doxorubicin (PLD) and daunorubicin citrate liposome (DNX), the combined treatment adriamycin-bleomycin-vincristine (ABV) and bleomycin-vincristine (BV), Paclitaxel and Interferon-alfa. In patients with limited skin localization, the local treatment can play an important role. Local medical therapy is based on the use of alitretinoin, antineoplastic drugs vincristine, vinblastine and bleomycin and Sodium Tetradecyl Sulfate (STS). In addition to medical therapy, physical treatment, such as cryotherapy and radiotherapy, are also commonly used.
Topics: Antineoplastic Agents; Antiretroviral Therapy, Highly Active; HIV Infections; Humans; Sarcoma, Kaposi
PubMed: 29272026
DOI: 10.26355/eurrev_201712_14036 -
Translational Cancer Research Sep 2019To evaluate the efficacy and safety of liposome-paclitaxel (L-PTX)/L-PTX plus S-1 in advanced gastric cancer patients with poor performance status (PS).
BACKGROUND
To evaluate the efficacy and safety of liposome-paclitaxel (L-PTX)/L-PTX plus S-1 in advanced gastric cancer patients with poor performance status (PS).
METHODS
We performed this retrospective study on 17 advanced gastric cancer patients with poor PS [rated as ≥2 based on the Eastern Cooperative Oncology Group (ECOG) scale] who underwent the following chemotherapy regimen: (I) L-PTX single-agent: L-PTX 60-80 mg/m given on days 1 and 8, in a 21-day cycle; (II) timed sequential (TS) regimen: L-PTX 60-80 mg/m given on days 1 and 8. S-1, 40-60 mg/m twice a day on days 1-14, in a 21-day cycle. Initially, some patients could not tolerate the 2-drug combination chemotherapy regimen, only L-PTX single-agent was given. After the patient's physical condition was improved, plus S-1 was also given.
RESULTS
A total of 17 patients were studied. No complete response (CR) or partial response (PR) were observed in six patients, accounting for 35.29% (6/17). Stable disease (SD) was observed in five patients, accounting for 29.41% (5/17), and progressive disease (PD) in 6, accounting for 35.29% (6/17). The objective response and disease control rates were 35.29% (6/17) and 64.71% (11/17), respectively. The median progression-free survival (PFS) and median overall survival (OS) were 6.50 months [95% confidence interval (CI): 4.81-8.20] and 13.00 months (95% CI: 0.00-33.65), respectively. The most common hematological toxicities were neutropenia and anemia.
CONCLUSIONS
L-PTX/L-PTX plus S-1 in the treatment of advanced gastric cancer patients with poor PS can prolong the patients' PFS and OS, and the toxicity is tolerable.
PubMed: 35116918
DOI: 10.21037/tcr.2019.08.17 -
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 -
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