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Journal For Immunotherapy of Cancer Feb 2023The standard neoadjuvant treatments in patients with esophageal squamous cell carcinoma (ESCC) still have either poor safety or efficacy. Better therapies are needed in...
BACKGROUND
The standard neoadjuvant treatments in patients with esophageal squamous cell carcinoma (ESCC) still have either poor safety or efficacy. Better therapies are needed in China.
METHODS
This was an open-label, single-arm, phase 2 trial. Patients with potentially resectable ESCC (cT1b-3, Nany, M0 or T4a, N0-1, or M0) received preoperative intravenous sintilimab plus triplet chemotherapy (liposomal paclitaxel, cisplatin, and S-1) every 3 weeks for two cycles. The primary endpoints were safety and surgical feasibility; the secondary endpoint was major pathological response (MPR) rate. Genomic biomarkers (genetic mutations, tumor mutational burden (TMB), circulating tumor DNA status and immune microenvironment) in baseline tumor samples were investigated.
RESULTS
All 30 patients completed two cycles of neoadjuvant treatment and underwent surgical resection. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 36.7% (11/30) of patients. The most frequent TRAEs were decreased white cell count (76.7%), anemia (76.7%), and decreased neutrophil count (73.3%). All TRAEs were hematological toxicities; none caused ≥30 days surgical delay. The MPR and pathological complete response (pCR) rates were 50.0% (15/30; 95% CI 33.2 to 66.9) and 20.0% (6/30; 95% CI 9.5 to 37.3), respectively. Patients with higher TMB and more clonal mutations were more likely to respond. ERBB2 alterations and ctDNA high-releaser status have a negative correlation with neoadjuvant ICI response. No significant difference was observed between therapeutic response and tumor immune microenvironment.
CONCLUSIONS
Neoadjuvant sintilimab plus platinum-based triplet chemotherapy appeared safe and feasible, did not delay surgery and induced a pCR rate of 20.0% in patients with potentially resectable ESCC.
TRIAL REGISTRATION NUMBER
NCT03946969.
Topics: Humans; Esophageal Squamous Cell Carcinoma; Neoadjuvant Therapy; Esophageal Neoplasms; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Tumor Microenvironment
PubMed: 36759013
DOI: 10.1136/jitc-2022-005830 -
Cancers Nov 2021Hyperproliferative skin diseases (HSD) are a group of diseases that include cancers, pre-cancerous lesions and diseases of unknown etiology that present different skin... (Review)
Review
Hyperproliferative skin diseases (HSD) are a group of diseases that include cancers, pre-cancerous lesions and diseases of unknown etiology that present different skin manifestations in terms of the degree and distribution of the injuries. Anti-proliferative agents used to treat these diseases are so diverse, including 5-aminolevulinic acid, 5-fluorouracil, imiquimod, methotrexate, paclitaxel, podophyllotoxin, realgar, and corticosteroids in general. These drugs usually have low aqueous solubility, which consequently decreases skin permeation. Thus, their incorporation in lipid nanocarriers has been proposed with the main objective to increase the effectiveness of topical treatment and reduce side effects. This manuscript aims to describe the advantages of using lipid nanoparticles and liposomes that can be used to load diversity of chemically different drugs for the treatment of HSD.
PubMed: 34830774
DOI: 10.3390/cancers13225619 -
Journal of Advanced Research Jul 2023Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various...
INTRODUCTION
Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various targeted drug-delivery systems, including nanoparticles and liposomes, are effective for MDR cancer treatment, their efficacy is restricted by immunosuppressive tumor microenvironment (TME).
METHODS
Ginsenosides Rg3 was used to formulate unique Rg3-based liposomes loaded with PTX to establish Rg3-PTX-LPs, which were prepared by the thin-film hydration method. The stability of the Rg3-PTX-LPs was evaluated by particle size analysis through dynamic light scattering. The active targeting effect of Rg3-based liposomes was examined in an MCF-7/T xenograft model by an in a vivo imaging system. To evaluate the antitumor activity and mechanism of Rg3-PTX-LP, MTT, apoptosis assays, TAM regulation, and TME remodeling were performed in MCF-7/T cells in vitro and in vivo.
RESULTS
Rg3-PTX-LPs could specifically distribute to MCF7/T cancer cells and TME simultaneously, mainly through the recognition of GLUT-1. The drug resistance reversing capability and in vivo antitumor effect of Rg3-PTX-LPs were significantly improved compared with conventional cholesterol liposomes. The TME remodeling mechanisms of Rg3-PTX-LPs included inhibiting IL-6/STAT3/p-STAT3 pathway activation to repolarize protumor M2 macrophages to antitumor M1 phenotype, suppressing myeloid-derived suppressor cells (MDSCs), decreasing tumor-associated fibroblasts (TAFs) and collagen fibers in TME, and promoting apoptosis of tumor cells. Hence, through the dual effects of targeting tumor cells and TME remodeling, Rg3-PTX-LPs achieved a high tumor inhibition rate of 90.3%.
CONCLUSION
Our multifunctional Rg3-based liposome developed in the present study offered a promising strategy for rescuing the drug resistance tumor treatment.
Topics: Humans; Paclitaxel; Liposomes; Ginsenosides; Tumor Microenvironment; Lipopolysaccharides; Neoplasms
PubMed: 36167294
DOI: 10.1016/j.jare.2022.09.007 -
Journal of Clinical Oncology : Official... Apr 2020A phase II study (ClinicalTrials.gov identifier: NCT00628251) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline... (Comparative Study)
Comparative Study Randomized Controlled Trial
Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial.
PURPOSE
A phase II study (ClinicalTrials.gov identifier: NCT00628251) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.
PATIENTS AND METHODS
In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician's choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population.
RESULTS
Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; = .013; median, 13.4 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy.
CONCLUSION
Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Genes, BRCA1; Genes, BRCA2; Germ-Line Mutation; Humans; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Phthalazines; Piperazines; Platinum Compounds
PubMed: 32073956
DOI: 10.1200/JCO.19.02745 -
European Journal of Cardio-thoracic... Jul 2016Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent... (Review)
Review
Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of 'theranostic' multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future.
Topics: Ablation Techniques; Antineoplastic Agents; Dendrimers; Drug Delivery Systems; Gene Transfer Techniques; Humans; Liposomes; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Micelles; Nanoparticles; Nanotechnology; Nanotubes, Carbon; Quantum Dots; Surgery, Computer-Assisted; Thoracic Surgical Procedures
PubMed: 26843431
DOI: 10.1093/ejcts/ezw002 -
Chinese Clinical Oncology Dec 2018Epithelial ovarian cancer (EOC) is a common malignant disease, which remains asymptomatic for a prolonged period of time and is usually diagnosed at advanced stages.... (Review)
Review
Epithelial ovarian cancer (EOC) is a common malignant disease, which remains asymptomatic for a prolonged period of time and is usually diagnosed at advanced stages. Cytoreductive surgery is a backbone of EOC treatment. Wherever possible, EOC patients are subjected to primary debulking surgery (PDS) with the aim to remove all visible tumor lumps. Some patients cannot undergo PDS due to extensive disease spread and/or high risk of perioperative morbidity, therefore they are subjected to neoadjuvant chemotherapy (NACT) before the surgery. Therapy given before surgery or as adjuvant treatment usually consists of combination of carboplatin and paclitaxel. Gemcitabine, topotecan, pegylated liposomal doxorubicin and poly ADP ribose polymerase inhibitors (PARPi) are commonly used for the management of EOC relapses. Consideration of BRCA1/2 germ-line and somatic status is getting increasingly important for the proper treatment planning.
Topics: Cytoreduction Surgical Procedures; Female; Humans; Neoadjuvant Therapy; Ovarian Neoplasms
PubMed: 30509078
DOI: 10.21037/cco.2018.10.06 -
Cancer Dec 2019The majority of patients with advanced ovarian cancer progress after first-line therapy and require further treatment. Tumor biology, prior chemotherapy, responses to... (Review)
Review
The majority of patients with advanced ovarian cancer progress after first-line therapy and require further treatment. Tumor biology, prior chemotherapy, responses to previous therapy, performance status, and toxicity are the characteristics that influence treatment choice. These criteria have been linked to the time between relapse and last platinum therapy: the platinum-free interval. Today, patients are classified as either those who are eligible for a new platinum-based therapy or those for whom platinum is not an option. A nonplatinum regimen should be administered to patients who are not candidates for platinum re-treatment. This group includes patients with early relapse after, or progression during, previous platinum-based chemotherapy and patients with platinum intolerability. A single agent such as weekly paclitaxel, pegylated liposomal doxorubicin (PLD), gemcitabine, or topotecan represents the standard. For patients not treated with bevacizumab in the first line, this drug should be added to chemotherapy. For patients for whom platinum rechallenge is an option (because they are potentially platinum-responsive), different strategies are available with the incorporation of biological drugs targeting angiogenesis or the mechanisms of DNA repair. A BRCA mutation status predicts a better response to platinum and poly(adenosine diphosphate-ribose) polymerase (PARP) inhibition. PARP inhibitors and antiangiogenic drugs have proven efficacy as maintenance therapy after chemotherapy and concurrently with chemotherapy, respectively. These agents have changed current practice, although few biomarkers are available to guide decisions. Patients potentially responsive to platinum who cannot receive the drug again can be treated with a combination of trabectedin and PLD, the most active nonplatinum therapy in this setting.
Topics: Carcinoma, Ovarian Epithelial; Female; Humans; Neoplasm Recurrence, Local
PubMed: 31967680
DOI: 10.1002/cncr.32500 -
The Lancet Regional Health. Western... Nov 2023Previous studies demonstrated that induction chemotherapy (IC) followed by de-escalated chemoradiotherapy adapted to tumor response was effective in treating childhood...
Paclitaxel liposome, cisplatin and 5-fluorouracil-based induction chemotherapy followed by de-escalated intensity-modulated radiotherapy with concurrent cisplatin in stage IVA-IVB childhood nasopharyngeal carcinoma in endemic area: a phase II, single-arm trial.
BACKGROUND
Previous studies demonstrated that induction chemotherapy (IC) followed by de-escalated chemoradiotherapy adapted to tumor response was effective in treating childhood nasopharyngeal carcinoma (NPC), but the toxicity profile of this treatment strategy, and whether childhood patients with advanced stages can obtain enough benefits from it requires further investigation.
METHODS
We conducted a single-center phase II trial (NCT03020329). All participants received 3 cycles of paclitaxel liposome, cisplatin and 5-fluorouracil (TPF)-based IC. Patients who showed complete or partial response received de-escalated radiotherapy of 60 Gy with 3 cycles of concurrent cisplatin, and those who showed stable or progressive disease received standard-dose radiotherapy of 70 Gy with concurrent cisplatin. The primary endpoint was the complete response (CR) rate at the end of concurrent chemoradiotherapy (CCRT).
FINDINGS
From November 2016 to March 2021, 44 patients were recruited in the cohort. The CR rate was 80% (35/44, 95% CI, 65-90) of the whole cohort. All patients achieved CR 3 months after CCRT. By the last follow-up, the 3-year progression-free survival and overall survival were 91% (95% CI, 82-99) and 100% respectively. Dry mouth was the most common late toxicity, with an incidence of 41% (18/44), followed by skin fibrosis and hearing impairment. No patient suffered from severe late toxicity and growth retardation.
INTERPRETATION
Our results proved the efficacy and safety of TPF regimen followed by de-escalated radiotherapy with concurrent cisplatin in treating stage IVa-b childhood NPC patients.
FUNDING
A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
PubMed: 37691885
DOI: 10.1016/j.lanwpc.2023.100895 -
Frontiers in Pharmacology 2024Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of...
Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of regional chemotherapy using paclitaxel, albumin-paclitaxel, and liposome-encapsulated albumin-paclitaxel via subserosal injection in rat models employing nuclear medicine and molecular imaging technology. Nine Sprague Dawley rats were divided into three groups: paclitaxel ( = 3), albumin-paclitaxel nano-particles (APNs; = 3), and liposome-encapsulated APNs ( = 3). [I]Iodo-paclitaxel ([I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using -butylstannyl substituted paclitaxel as the precursor. Albumin-[I]iodo-paclitaxel nanoparticles ([I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[I]APNs) were prepared by thin-film hydration using DSPE-PEG2000, HSPC, and cholesterol. The rats in each group were injected with each test drug into the subserosa of the stomach antrum. After predetermined times (30 min, 2, 4, 8 h, and 24 h), molecular images of nuclear medicine were acquired using single-photon emission computed tomography/computed tomography. Paclitaxel, APNs, and L-APNs showed a high cumulative distribution in the stomach, with L-APNs showing the largest area under the curve. Most drugs administered via the gastric subserosal route are distributed in the stomach and intestines, with a low uptake of less than 1% in other major organs. The time to reach the maximum concentration in the intestine for L-APNs, paclitaxel, and APNs was 6.67, 5.33, and 4.00 h, respectively. These preliminary results imply that L-APNs have the potential to serve as a novel paclitaxel preparation method for the regional treatment of gastric cancer.
PubMed: 38904000
DOI: 10.3389/fphar.2024.1381406 -
Cancers May 2021Bladder cancer (BC) is the second most common cancer of the urinary tract in men and the fourth most common cancer in women, and its incidence rises with age. There are... (Review)
Review
Bladder cancer (BC) is the second most common cancer of the urinary tract in men and the fourth most common cancer in women, and its incidence rises with age. There are many conventional methods for diagnosis and treatment of BC. There are some current biomarkers and clinical tests for the diagnosis and treatment of BC. For example, radiotherapy combined with chemotherapy and surgical, but residual tumor cells mostly cause tumor recurrence. In addition, chemotherapy after transurethral resection causes high side effects, and lack of selectivity, and low sensitivity in sensing. Therefore, it is essential to improve new procedures for the diagnosis and treatment of BC. Nanotechnology has recently sparked an interest in a variety of areas, including medicine, chemistry, physics, and biology. Nanoparticles (NP) have been used in tumor therapies as appropriate tools for enhancing drug delivery efficacy and enabling therapeutic performance. It is noteworthy, nanomaterial could be reduced the limitation of conventional cancer diagnosis and treatments. Since, the major disadvantages of therapeutic drugs are their insolubility in an aqueous solvent, for instance, paclitaxel (PTX) is one of the important therapeutic agents utilized to treating BC, due to its ability to prevent cancer cell growth. However, its major problem is the poor solubility, which has confirmed to be a challenge when improving stable formulations for BC treatment. In order to reduce this challenge, anti-cancer drugs can be loaded into NPs that can improve water solubility. In our review, we state several nanosystem, which can effective and useful for the diagnosis, treatment of BC. We investigate the function of metal NPs, polymeric NPs, liposomes, and exosomes accompanied therapeutic agents for BC Therapy, and then focused on the potential of nanotechnology to improve conventional approaches in sensing.
PubMed: 34063088
DOI: 10.3390/cancers13092214