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International Journal of Molecular... Mar 2023(), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The... (Review)
Review
(), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The asymptomatic status of the dormant bacteria escalates to the transmissible, active form when the host's immune system becomes debilitated. The current front-line treatment regimen for drug-sensitive (DS) strains is a 6-month protocol involving four different drugs that requires stringent adherence to avoid relapse and resistance. Poverty, difficulty to access proper treatment, and lack of patient compliance contributed to the emergence of more sinister drug-resistant (DR) strains, which demand a longer duration of treatment with more toxic and more expensive drugs compared to the first-line regimen. Only three new drugs, bedaquiline (BDQ) and the two nitroimidazole derivatives delamanid (DLM) and pretomanid (PMD) were approved in the last decade for treatment of TB-the first anti-TB drugs with novel mode of actions to be introduced to the market in more than 50 years-reflecting the attrition rates in the development and approval of new anti-TB drugs. Herein, we will discuss the pathogenesis, current treatment protocols and challenges to the TB control efforts. This review also aims to highlight several small molecules that have recently been identified as promising preclinical and clinical anti-TB drug candidates that inhibit new protein targets in .
Topics: Humans; Antitubercular Agents; Tuberculosis; Mycobacterium tuberculosis; Drug Delivery Systems; Clinical Protocols; Tuberculosis, Multidrug-Resistant
PubMed: 36982277
DOI: 10.3390/ijms24065202 -
Nutrients Jun 2023The aim of this study was to assess the available evidence regarding the effect of a variety of fasting-like regimens on preventing chemotherapy-related side effects.... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to assess the available evidence regarding the effect of a variety of fasting-like regimens on preventing chemotherapy-related side effects. PubMed, Scopus and Embase were used to select the studies for this review, which concluded on 24 November 2022. All types of clinical trials and case series reporting chemotherapy toxicity associated with fasting regimens and any comparison were considered. A total of 283 records were identified, of which 274 were excluded, leaving only nine studies that met the inclusion criteria. Five of these trials were randomized. Overall, moderate to high-quality evidence showed that several fasting regimens did not provide benefits compared to a conventional diet or other comparators in reducing the risk of adverse events. The overall pooled estimate for a variety of fasting regime when compared to non-fasting, indicated no significant difference in the side effects (RR = 1.10; 95% CI: 0.77-1.59; = 10%, = 0.60), including neutropenia alone (RR = 1.33; 95% CI: 0.90-1.97; = 0%, = 0.15). A sensitivity analysis confirmed these results. Based on our systematic review and meta-analysis, there is currently no evidence supporting the superiority of therapeutic fasting over non-fasting in preventing chemotherapy toxicity. The development of cancer treatment that do not entail toxicities remains imperative.
Topics: Humans; Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Drug-Related Side Effects and Adverse Reactions
PubMed: 37375570
DOI: 10.3390/nu15122666 -
British Journal of Haematology Nov 2016In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and...
In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 11·4 years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 12·7 and 8·5 years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12 years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Clinical Trials, Phase II as Topic; Female; Follow-Up Studies; Humans; Lymphoma, Mantle-Cell; Male; Middle Aged; Mortality; Neoplasm Staging; Prognosis; Recurrence; Remission Induction; Treatment Outcome
PubMed: 27378674
DOI: 10.1111/bjh.14241 -
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 -
The American Journal of Managed Care Jan 2019Pancreatic cancer remains a disease that is difficult to treat due to a typically late presentation, relatively high resistance to chemotherapy, and lack of effective... (Review)
Review
Pancreatic cancer remains a disease that is difficult to treat due to a typically late presentation, relatively high resistance to chemotherapy, and lack of effective targeted therapies. The standard of care relies on cytotoxic chemotherapy, primarily FOLFIRINOX and gemcitabine-based regimens. Dose modifications and/or the use of alternative combinations can reduce adverse effects, but these regimens remain highly toxic. As a result, long-term survival is low for patients with advanced or metastatic disease. There is a great need for novel anticancer agents that provide efficacy with minimal toxicity. Currently, inhibitors of immune tolerance and immune checkpoint inhibitors; PARP inhibitors; novel cytotoxic chemotherapies, such as trifluridine/tipiracil; and modifiers of the tumor microenvironment, such as pegylated hyaluronidase, are in clinical trials for the treatment of pancreatic cancer. This activity will review the current treatment landscape and preview emerging therapies for the treatment of advanced pancreatic cancer.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Humans; Hyaluronoglucosaminidase; Immune Tolerance; Microsatellite Instability; Neoplasm Staging; Palliative Care; Pancreatic Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Protein Kinase Inhibitors; Quality of Life; Risk Factors; Terminal Care; Tumor Microenvironment
PubMed: 30681819
DOI: No ID Found -
Critical Reviews in Oncology/hematology Feb 2017Recent years have highlighted significant progress in understanding the underlying genetic and epigenetic signatures of acute myeloid leukemia(AML). Most importantly,... (Review)
Review
Recent years have highlighted significant progress in understanding the underlying genetic and epigenetic signatures of acute myeloid leukemia(AML). Most importantly, novel chemotherapy and targeted strategies have led to improved outcomes in selected genetic subsets. AML is a remarkably heterogeneous disease, and individualized therapies for disease-specific characteristics (considering patients' age, cytogenetics, and mutations) could yield better outcomes. Compared with the historical 5-to 10-year survival rate of 10%, the survival of patients who undergo modern treatment approaches reaches up to 40-50%, and for specific subsets, the improvements are even more dramatic; for example, in acute promyelocytic leukemia, the use of all-trans retinoic acid and arsenic trioxide improved survival from 30 to 40% up to 80 to 90%. Similar progress has been documented in core-binding-factor-AML, with an increase in survival from 30% to 80% upon the use of high-dose cytarabine/fludarabine/granulocyte colony-stimulating factor combination regimens. AML treatment was also recently influenced by the discovery of the superiority of regimens with higher dose Ara-C and nucleoside analogues compared with the "7+3"regimen, with about a 20% improvement in overall survival. Despite these significant differences, most centers continue to use the "7+3" regimen, and greater awareness will improve the outcome. The discovery of targetable molecular abnormalities and recent studies of targeted therapies (gemtuzumab ozagomycin, FLT3 inhibitors, isocitrate dehydrogenase inhibitors, and epigenetic therapies), future use of checkpoint inhibitors and other immune therapies such as chimeric antigen receptor T-cells, and maintenance strategies based on the minimal residual disease evaluation represent novel, exciting clinical leads aimed to improve AML outcomes in the near future.
Topics: Adult; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Humans; Leukemia, Myeloid, Acute; Prognosis; Survival Rate
PubMed: 28109402
DOI: 10.1016/j.critrevonc.2016.12.004 -
Clinical Lymphoma, Myeloma & Leukemia Jan 2020The advent of new, more effective, and less toxic therapies has revolutionized the management of multiple myeloma in the past decade. Despite the availability of new... (Review)
Review
The advent of new, more effective, and less toxic therapies has revolutionized the management of multiple myeloma in the past decade. Despite the availability of new treatments, most patients with multiple myeloma will become refractory to the therapies that currently comprise the hematologic standard of care for the malignancy, including proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies. Moreover, in recent years, a new subset of patients with multiple myeloma refractory to all 3 of these agents has emerged. This population, for whom a clear treatment paradigm has remained undefined, has been characterized by poor survival outcomes. The current approaches to the treatment of triple-class refractory disease are limited and include conventional chemotherapy, salvage autologous stem cell transplantation, and recycling previous regimens, each of which have generally had short-lived efficacy. It is anticipated that additional agents will be available for triple-refractory disease in the near future, including selinexor, chimeric antigen receptor T-cell therapy, and next-generation monoclonal antibodies. The development and further refinement of novel treatments for this subset of patients should be considered a key clinical and research priority.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Multiple Myeloma
PubMed: 31767529
DOI: 10.1016/j.clml.2019.09.621 -
Current Oncology Reports Apr 2024This review describes the most relevant studies found in the scientific literature regarding metronomic chemotherapy (MCT) in the geriatric oncology population to... (Review)
Review
PURPOSE OF REVIEW
This review describes the most relevant studies found in the scientific literature regarding metronomic chemotherapy (MCT) in the geriatric oncology population to support its use as a feasible treatment of care in the frail elderly patients.
RECENT FINDINGS
Recent years have seen a reevaluation of cancer chemotherapeutic drugs and MCT is an emerging schedule in phase II and III clinical trials. Ageing is one of the risk factors for the development of cancer, the incidence of whom increases dramatically in people who live longer. To date, standard oncological protocols involve chemotherapeutic drugs in short cycles of therapy at the maximum tolerated dose (MTD). Although these therapeutic regimens may be successful, they can cause important adverse drug reactions, especially in elderly or frail patients. MCT is a different modality of delivery of chemotherapeutic drugs (frequent low dose for prolonged time) and it looks at the overcoming of the limitations and disadvantages of MTD, in particular the toxicity aspect. We reviewed the experience of clinicians who have used MCT in clinical trials enrolling elderly patients with different cancer types.
Topics: Humans; Aged; Antineoplastic Agents; Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38448722
DOI: 10.1007/s11912-024-01505-w -
International Journal of Molecular... Dec 2019Thyroid cancer is the most common endocrine malignancy. Most thyroid cancer types respond well to conventional treatment consisting of surgery and radioactive iodine... (Meta-Analysis)
Meta-Analysis Review
Thyroid cancer is the most common endocrine malignancy. Most thyroid cancer types respond well to conventional treatment consisting of surgery and radioactive iodine (RAI) therapy. Unfortunately, some thyroid cancer types are resistant to surgical and RAI therapy. Multikinase inhibitors (MKIs) can be used in the treatment of advanced refractory thyroid cancers. The objective of this review is to give an update on MKI treatment (lenvatinib, sorafenib, sunitinib, cabozantinib, pazopanib, vandetanib) of thyroid cancer, regarding its efficacy and safety profile. We evaluated 212 articles through a PubMed search. A total of 20 articles met the inclusion and none the exclusion criteria. The studies showed promising progression-free survival rates compared to placebo treatment from earlier studies and similar or better results compared to the SELECT and DECISION trials. Adverse effects (AEs) are substantial in the treatment with MKIs. Almost all patients treated with these novel drugs experienced AEs. It is therefore crucial to focus on the management of AEs for a decent long-term outcome. The AEs are often more severe in patients with high efficacy of MKIs, which could indicate a correlation. Taken together, the novel therapeutic regimen with MKIs has shown favorable results in otherwise treatment-resistant thyroid cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Humans; Molecular Targeted Therapy; Prognosis; Protein Kinase Inhibitors; Thyroid Neoplasms; Treatment Outcome
PubMed: 31861373
DOI: 10.3390/ijms21010010 -
The Oncologist 2001ASCO 2001 was a banner year for innovative systemic therapy for sarcomas. Imatinib mesylate (STI571, Gleevec) shows clear activity not only in chronic myelogenous... (Review)
Review
ASCO 2001 was a banner year for innovative systemic therapy for sarcomas. Imatinib mesylate (STI571, Gleevec) shows clear activity not only in chronic myelogenous leukemia, for which the drug received Food and Drug Administration approval, but also in gastrointestinal stromal tumors as well, by virtue of imatinib mesylate binding to the abl, kit, and platelet-derived growth factor receptor tyrosine kinases. Ecteinascidin-743 (ET-743) demonstrates activity against a fraction of other soft-tissue sarcomas. Gemcitabine-based regimens show at least some activity against a subset of soft-tissue sarcomas. Given the lack of new agents for sarcoma therapy since the development of ifosfamide, these studies give hope that the term "effective systemic therapy for sarcoma" might become a reality.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Clinical Trials as Topic; Humans; Sarcoma
PubMed: 11524551
DOI: 10.1634/theoncologist.6-4-333