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Expert Opinion on Therapeutic Patents 2016Paclitaxel and docetaxel were two epoch-making anticancer drugs and have been successfully used in chemotherapy for a variety of cancer types. In the year 2010, a new... (Review)
Review
INTRODUCTION
Paclitaxel and docetaxel were two epoch-making anticancer drugs and have been successfully used in chemotherapy for a variety of cancer types. In the year 2010, a new taxane, cabazitaxel, was approved by FDA for use in combination with prednisone for the treatment of metastatic hormone-refractory prostate cancer. Albumin-bound paclitaxel (nab™-paclitaxel; abraxane) nanodroplet formulation was another notable invention (FDA approval 2005 for refractory, metastatic, or relapsed breast cancer). Abraxane in combination with gemcitabine for the treatment of pancreatic cancer was approved by FDA in 2013. Accordingly, there have been a huge number of patent applications dealing with taxane anticancer agents in the last 5 years. Thus, it is a good time to review the progress in this area and find the next wave for new developments.
AREA COVERED
This review covers the patent literature from the year 2010 to early 2015 on various aspects of taxane-based chemotherapies and drug developments.
EXPERT OPINION
Three FDA-approved taxane anticancer drugs will continue to expand their therapeutic applications, especially through drug combinations and new formulations. Inspired by the success of abraxane, new nano-formulations are emerging. Highly potent new-generation taxanes will play a key role in the development of efficacious tumor-targeted drug delivery systems.
Topics: Animals; Antineoplastic Agents; Docetaxel; Drug Delivery Systems; Drug Design; Female; Humans; Male; Nanostructures; Neoplasms; Paclitaxel; Patents as Topic; Taxoids
PubMed: 26651178
DOI: 10.1517/13543776.2016.1111872 -
Journal of Clinical Monitoring and... Dec 2022Accurate measurement of respiratory rate (RR) in neonates is challenging due to high neonatal RR variability (RRV). There is growing evidence that RRV measurement could...
Accurate measurement of respiratory rate (RR) in neonates is challenging due to high neonatal RR variability (RRV). There is growing evidence that RRV measurement could inform and guide neonatal care. We sought to quantify neonatal RRV during a clinical study in which we compared multiparameter continuous physiological monitoring (MCPM) devices. Measurements of capnography-recorded exhaled carbon dioxide across 60-s epochs were collected from neonates admitted to the neonatal unit at Aga Khan University-Nairobi hospital. Breaths were manually counted from capnograms and using an automated signal detection algorithm which also calculated mean and median RR for each epoch. Outcome measures were between- and within-neonate RRV, between- and within-epoch RRV, and 95% limits of agreement, bias, and root-mean-square deviation. Twenty-seven neonates were included, with 130 epochs analysed. Mean manual breath count (MBC) was 48 breaths per minute. Median RRV ranged from 11.5% (interquartile range (IQR) 6.8-18.9%) to 28.1% (IQR 23.5-36.7%). Bias and limits of agreement for MBC vs algorithm-derived breath count, MBC vs algorithm-derived median breath rate, MBC vs algorithm-derived mean breath rate were - 0.5 (- 2.7, 1.66), - 3.16 (- 12.12, 5.8), and - 3.99 (- 11.3, 3.32), respectively. The marked RRV highlights the challenge of performing accurate RR measurements in neonates. More research is required to optimize the use of RRV to improve care. When evaluating MCPM devices, accuracy thresholds should be less stringent in newborns due to increased RRV. Lastly, median RR, which discounts the impact of extreme outliers, may be more reflective of the underlying physiological control of breathing.
Topics: Infant, Newborn; Humans; Respiratory Rate; Kenya; Capnography; Monitoring, Physiologic; Respiration
PubMed: 35332406
DOI: 10.1007/s10877-022-00840-2 -
Molecules (Basel, Switzerland) Jun 2023Cancer continues to pose a severe threat to global health, making pursuing effective treatments more critical than ever. Traditional therapies, although pivotal in... (Review)
Review
Cancer continues to pose a severe threat to global health, making pursuing effective treatments more critical than ever. Traditional therapies, although pivotal in managing cancer, encounter considerable challenges, including drug resistance, poor drug solubility, and difficulties targeting tumors, specifically limiting their overall efficacy. Nanomedicine's application in cancer therapy signals a new epoch, distinguished by the improvement of the specificity, efficacy, and tolerability of cancer treatments. This review explores the mechanisms and advantages of nanoparticle-mediated drug delivery, highlighting passive and active targeting strategies. Furthermore, it explores the transformative potential of nanomedicine in tumor therapeutics, delving into its applications across various treatment modalities, including surgery, chemotherapy, immunotherapy, radiotherapy, photodynamic and photothermal therapy, gene therapy, as well as tumor diagnosis and imaging. Meanwhile, the outlook of nanomedicine in tumor therapeutics is discussed, emphasizing the need for addressing toxicity concerns, improving drug delivery strategies, enhancing carrier stability and controlled release, simplifying nano-design, and exploring novel manufacturing technologies. Overall, integrating nanomedicine in cancer treatment holds immense potential for revolutionizing cancer therapeutics and improving patient outcomes.
Topics: Humans; Nanomedicine; Neoplasms; Drug Delivery Systems; Immunotherapy; Diagnostic Imaging; Nanoparticles
PubMed: 37446806
DOI: 10.3390/molecules28135145 -
BMC Cancer Aug 2020The optimal chemotherapy regimen for treating HIV associated NHL in low resource settings is unknown. We conducted a retrospective study to describe survival rates,...
BACKGROUND
The optimal chemotherapy regimen for treating HIV associated NHL in low resource settings is unknown. We conducted a retrospective study to describe survival rates, treatment response rates and adverse events in patients with HIV associated NHL treated with CHOP and dose adjusted-EPOCH regimens at the Uganda Cancer Institute.
METHODS
A retrospective study of patients diagnosed with HIV and lymphoma and treated at the Uganda Cancer Institute from 2016 to 2018 was done.
RESULTS
One hundred eight patients treated with CHOP and 12 patients treated with DA-EPOCH were analysed. Patients completing 6 or more cycles of chemotherapy were 51 (47%) in the CHOP group and 8 (67%) in the DA-EPOCH group. One year overall survival (OS) rate in patients treated with CHOP was 54.5% (95% CI, 42.8-64.8) and 80.2% (95% CI, 40.3-94.8) in those treated with DA-EPOCH. Factors associated with favourable survival were BMI 18.5-24.9 kg/m, (p = 0.03) and completion of 6 or more cycles of chemotherapy, (p < 0.001). The overall response rate was 40% in the CHOP group and 59% in the DA-EPOCH group. Severe adverse events occurred in 19 (18%) patients in the CHOP group and 3 (25%) in the DA-EPOCH group; these were neutropenia (CHOP = 13, 12%; DA-EPOCH = 2, 17%), anaemia (CHOP = 12, 12%; DA-EPOCH = 1, 8%), thrombocytopenia (CHOP = 7, 6%; DA-EPOCH = 0), sepsis (CHOP = 1), treatment related death (DA-EPOCH = 1) and hepatic encephalopathy (CHOP = 1).
CONCLUSION
Treatment of HIV associated NHL with curative intent using CHOP and infusional DA-EPOCH is feasible in low resource settings and associated with > 50% 1 year survival.
Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Female; HIV Infections; Hepatic Encephalopathy; Humans; Infusions, Intravenous; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Neutropenia; Prednisone; Retrospective Studies; Sepsis; Survival Rate; Thrombocytopenia; Time Factors; Treatment Outcome; Uganda; Vincristine
PubMed: 32831073
DOI: 10.1186/s12885-020-07305-2 -
Frontiers in Oncology 2023Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved... (Review)
Review
Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved treatments. Curative surgery for patients with early-stage lung cancer is the standard of care, but not all surgical treatments have a good prognosis. Adjuvant and neoadjuvant chemotherapy are used to improve the prognosis of patients with resectable lung cancer. Immunotherapy, an epoch-defining treatment, has improved curative effects, prognosis, and tolerability compared with traditional and ordinary cytotoxic chemotherapy, providing new hope for patients with non-small cell lung cancer (NSCLC). Immunotherapy-related clinical trials have reported encouraging clinical outcomes in their exploration of different types of perioperative immunotherapy, from neoadjuvant immune checkpoint inhibitor (ICI) monotherapy, neoadjuvant immune-combination therapy (chemoimmunotherapy, immunotherapy plus antiangiogenic therapy, immunotherapy plus radiotherapy, or concurrent chemoradiotherapy), adjuvant immunotherapy, and neoadjuvant combined adjuvant immunotherapy. Phase 3 studies such as IMpower 010 and CheckMate 816 reported survival benefits of perioperative immunotherapy for operable patients. This review summarizes up-to-date clinical studies and analyzes the efficiency and feasibility of different neoadjuvant therapies and biomarkers to identify optimal types of perioperative immunotherapy for NSCLC.
PubMed: 36761954
DOI: 10.3389/fonc.2023.1011810 -
Blood Advances Jun 2023The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone... (Clinical Trial)
Clinical Trial
The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) regimen for large B-cell lymphomas, but it is unknown whether Pola can be safely incorporated into intensified regimens (eg, dose-adjusted [DA]-EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab]) typically used for the highest risk histologies. This was a single-center, open-label, prospective clinical trial of 6 cycles of Pola-DA-EPCH-R (vincristine omitted) in aggressive large B-cell lymphomas. The primary end point was to estimate the safety of Pola-DA-EPCH-R as measured by the rate of dose-limiting toxicities (DLTs) in the first 2 cycles with prespecified suspension rules. Secondary and exploratory end points included efficacy and correlation with circulating tumor DNA (ctDNA) levels. We enrolled 18 patients on study, and with only 3 DLTs observed, the study met its primary end point for safety. There were 5 serious adverse events, including grade 3 febrile neutropenia (3, 17%), grade 3 colonic perforation in the setting of diverticulitis, and grade 5 sepsis/typhlitis. Among 17 evaluable patients, the best overall response rate was 100%, and the complete response rate was 76%. With a median follow-up of 12.9 months, 12-month event-free survival was 72%, and 12-month overall survival was 94%. No patient with undetectable ctDNA at the end of treatment has relapsed to date. Using Pola to replace vincristine in the DA-EPOCH-R regimen met its primary safety end point. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. This trial was registered at www.clinicaltrials.gov as #NCT04231877.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Etoposide; Lymphoma, Large B-Cell, Diffuse; Prednisone; Prospective Studies; Rituximab; Vincristine
PubMed: 36521030
DOI: 10.1182/bloodadvances.2022009145 -
Journal of Hematology & Oncology Jun 2018Bcr-Abl inhibitors paved the way of targeted therapy epoch. Imatinib was the first tyrosine kinase inhibitor to be discovered with high specificity for Bcr-Abl protein... (Review)
Review
Bcr-Abl inhibitors paved the way of targeted therapy epoch. Imatinib was the first tyrosine kinase inhibitor to be discovered with high specificity for Bcr-Abl protein resulting from t(9, 22)-derived Philadelphia chromosome. Although the specific targeting of that oncoprotein, several Bcr-Abl-dependent and Bcr-Abl-independent mechanisms of resistance to imatinib arose after becoming first-line therapy in chronic myelogenous leukemia (CML) treatment.Consequently, new specific drugs, namely dasatinib, nilotinib, bosutinib, and ponatinib, were rationally designed and approved for clinic to override resistances. Imatinib fine mechanisms of action had been elucidated to rationally develop those second- and third-generation inhibitors. Crystallographic and structure-activity relationship analysis, jointly to clinical data, were pivotal to shed light on this topic. More recently, preclinical evidence on bafetinib, rebastinib, tozasertib, danusertib, HG-7-85-01, GNF-2, and 1,3,4-thiadiazole derivatives lay promising foundations for better inhibitors to be approved for clinic in the near future.Notably, structural mechanisms of action and drug design exemplified by Bcr-Abl inhibitors have broad relevance to both break through resistances in CML treatment and develop inhibitors against other kinases as targeted chemotherapeutics.
Topics: Fusion Proteins, bcr-abl; Humans; Molecular Targeted Therapy; Protein Kinase Inhibitors; Structure-Activity Relationship; Treatment Outcome
PubMed: 29925402
DOI: 10.1186/s13045-018-0624-2 -
Revista Peruana de Medicina... 2017Non-Hodgkin's lymphomas are common and comprise a heterogeneous group of neoplasms, with diffuse large B-cell lymphoma (DLBCL) accounting for more than 60% of cases.... (Review)
Review
Non-Hodgkin's lymphomas are common and comprise a heterogeneous group of neoplasms, with diffuse large B-cell lymphoma (DLBCL) accounting for more than 60% of cases. Moreover, DLBCL presents with a variety of clinical characteristics, genetic profiles, and therapeutic responses. We aimed to improve progression-free survival, total survival, and objective results in an DLBCL subgroup. However, another subgroup demonstrated poor responses. Therefore, it is necessary to design treatment programs based on clinical, immunohistochemical, and genetic profiles, grouping cases properly to identify correct therapeutic modalities for each lymphoma subtype. Currently, these neoplasms are classified as high- and low-risk lymphomas, and therapeutic regimens are being developed to complement conventional R-CHOP, such as R-DA-EPOCH, R2CHOP, IR-CHOP, VR-CHOP, and eveRCHOP, which are expected to improve outcomes.
Topics: Algorithms; Antineoplastic Combined Chemotherapy Protocols; Humans; Lymphoma, Large B-Cell, Diffuse
PubMed: 29267782
DOI: 10.17843/rpmesp.2017.343.2803 -
Cancer Medicine Jan 2020Aggressive non-Hodgkin lymphoma (NHL) is among the most common cancers in sub-Saharan Africa (SSA), where CHOP is standard treatment and outcomes are poor. To address...
Aggressive non-Hodgkin lymphoma (NHL) is among the most common cancers in sub-Saharan Africa (SSA), where CHOP is standard treatment and outcomes are poor. To address this, we treated 17 newly diagnosed adult patients in Malawi with Burkitt (n = 8), plasmablastic (n = 8), and primary effusion lymphoma (n = 1) with a modified EPOCH regimen between 2016 and 2019. Twelve patients (71%) were male and the median age was 40 years (range 16-63). Eleven (65%) were HIV infected, median CD4 count was 218 cells/µL (range 9-460), and nine (82%) had suppressed HIV RNA < 400 copies/mL. Patients received a median of six cycles (range 2-8) and median follow-up was 14 months (range 2-34) among patients still alive. Grade 3/4 neutropenia was observed in 26% of cycles and in 65% of patients. Sixteen (94%) responded to EPOCH and 10 (59%) achieved a complete response. One-year overall survival (OS) was 62% (95% confidence interval [CI], 42%-91%). Five patients (29%) died from progressive NHL and three (18%) from treatment-related complications. These data suggest EPOCH with setting-appropriate modifications may be a practical, safe, and effective option for improving high-risk NHL outcomes in Malawi and comparable settings, which deserves further prospective evaluation.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; CD4 Lymphocyte Count; Cyclophosphamide; Doxorubicin; Etoposide; Female; Follow-Up Studies; HIV Infections; Humans; Lymphoma, Non-Hodgkin; Malawi; Male; Middle Aged; Neutropenia; Prednisone; Progression-Free Survival; RNA, Viral; Vincristine; Young Adult
PubMed: 31705618
DOI: 10.1002/cam4.2631 -
Pediatric Research Jan 2023Child health is defined by a complex, dynamic network of genetic, cultural, nutritional, infectious, and environmental determinants at distinct, developmentally... (Review)
Review
Child health is defined by a complex, dynamic network of genetic, cultural, nutritional, infectious, and environmental determinants at distinct, developmentally determined epochs from preconception to adolescence. This network shapes the future of children, susceptibilities to adult diseases, and individual child health outcomes. Evolution selects characteristics during fetal life, infancy, childhood, and adolescence that adapt to predictable and unpredictable exposures/stresses by creating alternative developmental phenotype trajectories. While child health has improved in the United States and globally over the past 30 years, continued improvement requires access to data that fully represent the complexity of these interactions and to new analytic methods. Big Data and innovative data science methods provide tools to integrate multiple data dimensions for description of best clinical, predictive, and preventive practices, for reducing racial disparities in child health outcomes, for inclusion of patient and family input in medical assessments, and for defining individual disease risk, mechanisms, and therapies. However, leveraging these resources will require new strategies that intentionally address institutional, ethical, regulatory, cultural, technical, and systemic barriers as well as developing partnerships with children and families from diverse backgrounds that acknowledge historical sources of mistrust. We highlight existing pediatric Big Data initiatives and identify areas of future research. IMPACT: Big Data and data science can improve child health. This review highlights the importance for child health of child-specific and life course-based Big Data and data science strategies. This review provides recommendations for future pediatric-specific Big Data and data science research.
Topics: Humans; Pregnancy; Female; Child; United States; Child Health; Big Data; Data Science; Prenatal Care
PubMed: 35974162
DOI: 10.1038/s41390-022-02264-9