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Cancers May 2023Combined modality has represented a mainstay of treatment across many lymphoma histologies, given their sensitivity to both multi-agent chemotherapy and... (Review)
Review
Combined modality has represented a mainstay of treatment across many lymphoma histologies, given their sensitivity to both multi-agent chemotherapy and intermediate-dose radiotherapy. More recently, several new agents, including immunotherapies, have reshaped the therapeutic panorama of some lymphomas. In parallel, radiotherapy techniques have witnessed substantial improvement, accompanied by a growing understanding that radiation itself comes with an immune-mediated effect. Six decades after a metastatic lesion regression outside the irradiated field was first described, there is increasing evidence that a combination of radiotherapy and immunotherapy could boost an abscopal effect. This review focuses on the mechanisms underlying this interaction in the setting of lymphomas, and on the results of pivotal prospective studies. Furthermore, the available evidence on the concomitant use of radiotherapy and small molecules (i.e., lenalidomide, venetoclax, and ibrutinib), as well as brentuximab vedotin, and chimeric antigen receptor (CAR) T-cell therapy, is summarized. Currently, combining radiotherapy with new agents in patients who are affected by lymphomas appears feasible, particularly as a bridge to anti-CD19 autologous CAR T-cell infusion. However, more studies are required to assess these combinations, and preliminary data suggest only a synergistic rather than a curative effect.
PubMed: 37345088
DOI: 10.3390/cancers15102751 -
Frontiers in Microbiology 2019Humans and animals are infected by multiple endogenous and exogenous viruses but few agents cause overt tissue damage. We review the circumstances which favor overt... (Review)
Review
Humans and animals are infected by multiple endogenous and exogenous viruses but few agents cause overt tissue damage. We review the circumstances which favor overt disease expression. These can include intrinsic virulence of the agent, new agents acquired from heterologous species, the circumstances of infection such as dose and route, current infection with other agents which includes the composition of the microbiome at mucosal and other sites, past history of exposure to other infections as well as the immune status of the host. We also briefly discuss promising therapeutic strategies that can expand immune response patterns that minimize tissue damaging responses to viral infections.
PubMed: 31636623
DOI: 10.3389/fmicb.2019.02314 -
Revista Espanola de Quimioterapia :... Jun 2008Anidulafungin is a new echinocandin antifungal agent recently approved in Spain by the Spanish Drug Agency. As other echinocandins, it inhibits a selective target, 1,3-... (Review)
Review
Anidulafungin is a new echinocandin antifungal agent recently approved in Spain by the Spanish Drug Agency. As other echinocandins, it inhibits a selective target, 1,3- beta-D-glucan synthesis, a major structural component of the fungal cell wall which is not present in mammalian cells, this avoiding toxicity problems. It has fungicidal activity against many Candida spp., including fluconazole-resistant, and fungistatic activity against other yeast and moulds such as Aspergillus spp. Clinical trials have shown non-inferiority of anidulafungin to fluconazole for invasive, including candidemia, and non-invasive Candida infections. It is well-tolerated, and no drug-related serious adverse events have been reported. Anidulafungin, which has a very long half life, is slowly degraded by human peptidases and proteases and has a low drug-drug interaction profile based on its lack of interaction with the cytochrome P450 system. Thus, dosing adjustments of anidulafungin based on age, gender, body weight, disease status, concomitant therapy or renal or hepatic insufficiency is not necessary. As it does not interact with amphotericin B and voriconazole, cyclosporine, tacrolimus and other drugs, it can be used in combination with other antifungal agents and co-administered with immunosuppressant drugs. It is generally well-tolerated in clinical trials. Its most frequent adverse events are nausea, vomiting, moderate diarrhea, transient elevation of hepatic enzymes and headache. Some of the patients have mild, passing reactions such as facial blushing, nausea and dyspnea related with rapid intravenous perfusion. Its antifungal activity, clinical efficacy, safety profile, and pharmacokinetic characteristics make it a suitable alternative antifungal compound for therapy of mucosal candidiasis, candidemia and invasive candidiasis, above all in patients with some degree of renal and hepatic insufficiency.
Topics: Anidulafungin; Animals; Antifungal Agents; Disease Models, Animal; Echinocandins; Humans; Mycoses
PubMed: 18509769
DOI: No ID Found -
Microorganisms Jan 2022() is an oropharyngeal commensal agent of toddlers and the primary cause of osteoarticular infections in 6-23-month-old children. Knowing that the oropharynx of young...
() is an oropharyngeal commensal agent of toddlers and the primary cause of osteoarticular infections in 6-23-month-old children. Knowing that the oropharynx of young children is the reservoir and the portal of entry of , these results suggested that a viral infection may promote infection. In this narrative review, we report the current knowledge of the concomitance between and viral infections. This hypothesis was first suggested because some authors described that symptoms of viral infections were frequently concomitant with infection. Second, specific viral syndromes, such as hand, foot and mouth disease or stomatitis, have been described in children experiencing a infection. Moreover, some clusters of infection occurring in daycare centers were preceded by viral outbreaks. Third, the major viruses identified in patients during infection were human rhinovirus or coxsackievirus, which both belong to the Picornaviridae family and are known to facilitate bacterial infections. Finally, a temporal association was observed between human rhinovirus circulation and infection. Although highly probable, the role of viral infection in the pathophysiology remains unclear and is based on case description or temporal association. Molecular studies are needed.
PubMed: 35208685
DOI: 10.3390/microorganisms10020230 -
Journal of Clinical Medicine Jun 2023Roxadustat is a novel agent with a distinct mechanism of action compared to erythropoiesis-stimulating agents (ESAs) and a potentially different combination of effects... (Review)
Review
Roxadustat is a novel agent with a distinct mechanism of action compared to erythropoiesis-stimulating agents (ESAs) and a potentially different combination of effects on iron parameters. This narrative review describes the effects of roxadustat on iron parameters and on hemoglobin levels in the context of iron supplementation in patients with anemia of non-dialysis-dependent (NDD) or dialysis-dependent (DD) chronic kidney disease (CKD). Roxadustat use was associated with a greater reduction in serum ferritin levels than seen with ESAs and an increase in serum iron levels compared to a decrease with ESAs. Decreases in transferrin saturation in patients treated with roxadustat were relatively small and, in the case of patients with NDD CKD, not observed by Week 52. These changes reflect the concomitant increases in both serum iron and total iron-binding capacity. Compared to placebo and an ESA, roxadustat improved iron availability and increased erythropoiesis while requiring less intravenous iron use. Hepcidin levels generally decreased in patients who received roxadustat compared to baseline values in all CKD populations; these decreases appear to be more robust with roxadustat than with an ESA or placebo. The mechanisms behind the effects of roxadustat and ESAs on iron availability and stores and erythropoiesis appear to differ and should be considered holistically when treating anemia of CKD.
PubMed: 37445252
DOI: 10.3390/jcm12134217 -
Therapeutics and Clinical Risk... 2020Emicizumab, a humanized, bi-specific, monoclonal antibody subcutaneously administered, mimicking the function of FVIIIa, represents a milestone in treatment of patients... (Review)
Review
Emicizumab, a humanized, bi-specific, monoclonal antibody subcutaneously administered, mimicking the function of FVIIIa, represents a milestone in treatment of patients affected by hemophilia A complicated with inhibitors. The HAVEN 1 and 2 studies have clearly established its superiority compared to bypassing agents for routine prophylaxis in preventing or reducing bleeding episodes in adult and pediatric patients with inhibitors. However, its protection against bleeding is only partial, and concomitant use of a bypassing agent may be required with potential prothrombotic risk. The emicizumab Phase III trials (HAVEN 1, 2 and 4) have shown that the traditional bypassing agents, activated prothrombin complex concentrates or recombinant activated factor VII (rFVIIa), may be necessary for the treatment of breakthrough bleeds or surgery management. A post hoc analysis in particular has shown that the concomitant use of emicizumab and rFVIIa is safe and no thrombotic events have been described. The review describes the state of the art of the concomitant use of emicizumab and rFVIIa for treating acute bleeding and surgeries, its efficacy and safety and the lack of thrombotic events associated with this treatment modality. Data still derive mainly from HAVEN trials; however, the availability of emicizumab in clinical practice is progressively increasing the number of patients treated and no adverse events directly attributed to this agent have occurred. The availability of guidelines for the use and dosing of rFVIIa during emicizumab prophylaxis is useful in clinical practice for managing suspected or ongoing bleeding, emergency situations and elective invasive procedures. In the next years, careful prospective post-licensure surveillance to monitor safety of rFVIIa use during prophylaxis with emicizumab is highly recommended.
PubMed: 32547043
DOI: 10.2147/TCRM.S205310 -
Journal of Breast Cancer Jun 2017In the last few decades, neoadjuvant therapy for breast cancer has gained considerable therapeutic importance. Despite extensive clinical investigations, it has not yet... (Review)
Review
In the last few decades, neoadjuvant therapy for breast cancer has gained considerable therapeutic importance. Despite extensive clinical investigations, it has not yet been clarified whether neoadjuvant therapy would result in improved survival in comparison with the standard adjuvant setting in any subgroups of patients with breast cancer. Chemotherapy is especially effective in the treatment of endocrine insensitive tumors, and such ther-apeutic benefit can be assumed for patients with triple-negative, or hormone receptor-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, dose escalation, modification of the therapeutic regimens according to early tumor response, as well as the optimal sequence of administration are still matters of debate. There is a current debate between clinical experts regarding the concomitant and sequential administration of carboplatin and capecitabine, respectively, as part of the standard neoadjuvant treatment, as well as the use of bevacizumab, as part of the preoperative treatment. In case of HER2 positive tumors, an anti-HER2 agent can be administered as part of the preoperative treatment, and according to preliminary clinical data, dual HER2 blockade can also be reasonable. Further, chemotherapy-free regimens can be justified in highly endocrine sensitive tumors, while immune modulating agents may also gain particular importance in the case of certain subtypes of breast cancer. Several small-molecule targeted therapies are under clinical investigation and are expected to provide new neoadjuvant treatment options. However, novel, more predictive biomarkers are required for further evaluation of the neoadjuvant therapies, as well as the effect of novel targeted agents intended to be incorporated into neoadjuvant therapy.
PubMed: 28690648
DOI: 10.4048/jbc.2017.20.2.119 -
Expert Review of Cardiovascular Therapy Nov 2018Coronary artery disease (CAD) remains the leading cause of mortality and morbidity worldwide, and hypertension is its most prevalent modifiable risk factor. Patients... (Review)
Review
Coronary artery disease (CAD) remains the leading cause of mortality and morbidity worldwide, and hypertension is its most prevalent modifiable risk factor. Patients with CAD and concomitant hypertension are a special population with distinct physiologic and structural alterations. Optimal blood pressure (BP) control in this population has been linked with reduction in adverse outcomes, however, excessive lowering of BP could jeopardize myocardial and cerebral perfusion. Areas covered: Authors highlight the prevalence of the CAD and hypertension dyad, as well as the implications of various structural and physiological changes in this population. Subsequently, available data on optimal BP targets in such patients, and lastly the J-curve phenomenon as well as antihypertensive agent use are discussed. Expert commentary: Current guideline recommendations are based on data from trials such as SPRINT and ACCORD which did not specifically focus on the CAD population. Based on data from observational studies and post hoc analyses, the best therapeutic systolic (SBP) and diastolic (DBP) targets may be ~ 130 mmHg and ~ 80 mmHg, respectively. Caution should be taken to not lower SBP below 120 mmHg and DBP below 60 mmHg.
Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Coronary Artery Disease; Humans; Hypertension; Prevalence; Risk Factors
PubMed: 30295548
DOI: 10.1080/14779072.2018.1534069 -
Actas Dermo-sifiliograficas May 2015The aim of the present review is to provide an update on the most important recent studies on the use of etanercept in psoriatic arthritis (PsA). Using various... (Review)
Review
The aim of the present review is to provide an update on the most important recent studies on the use of etanercept in psoriatic arthritis (PsA). Using various assessment tools, such as the Disease Activity Score 28-joint count (DAS28), the PsA Response Criteria (PsARC), and the American College of Rheumatology (ACR) score, several authors have shown that etanercept can reduce the signs and symptoms of psoriatic arthritis and inhibit radiographic progression in studies with follow-up periods of up to 2 years. There is evidence that etanercept is effective in the treatment of psoriatic enthesitis, dactylitis, and axial joint disease as well as in disease affecting the skin and nails. In clinical trials, etanercept had a safety profile similar to that of placebo and this profile did not change over time. Cost-effectiveness models have found etanercept to be the most cost-effective tumor necrosis factor inhibitor in patients with psoriatic arthritis and mild to moderate psoriasis. Etanercept has a favorable risk-benefit profile in the short term. The concomitant use of methotrexate does not alter etanercept survival.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Clinical Trials as Topic; Cost-Benefit Analysis; Disease Progression; Drug Therapy, Combination; Etanercept; Humans; Immunosuppressive Agents; Meta-Analysis as Topic; Observational Studies as Topic; Receptors, Tumor Necrosis Factor; Risk Assessment; Severity of Illness Index; Therapeutic Equivalency
PubMed: 25455504
DOI: 10.1016/j.ad.2014.09.004 -
Advances in Therapy Nov 2023Cardiovascular (CV) events are the leading cause of death in prostate cancer. Men with prostate cancer are likely to have CV risk factors and use CV-related concomitant... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Cardiovascular (CV) events are the leading cause of death in prostate cancer. Men with prostate cancer are likely to have CV risk factors and use CV-related concomitant medications. In the phase 3 HERO study, a 54% lower incidence of major adverse cardiac events was reported in men treated with the oral gonadotropin-releasing hormone (GnRH) receptor antagonist, relugolix, vs leuprolide. Herein, we characterize the impact of concomitant CV therapies on efficacy and safety in the HERO study.
METHODS
In HERO, 930 men with advanced prostate cancer (APC) were randomized 2:1 and treated with relugolix (120 mg orally once daily; after single 360 mg loading dose) or leuprolide (injections every 3 months) for 48 weeks. Subgroups analyzed included men who received antihypertensives, antithrombotics, or lipid-modifying therapies (LMAs), as well as the most common drug classes (> 10%) and single most common agent within each class. Assessments included sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks and safety.
RESULTS
Antihypertensives, antithrombotics, and LMAs were utilized by 52.7%, 39.1%, and 39.6% of men in HERO, respectively. In the main subgroups, point estimates for sustained castration rates were generally consistent with overall estimates of relugolix and leuprolide observed in the overall population. Sustained castration rates were also mostly consistent for men taking the most common drug classes and individual agents in each class (losartan [n = 103]: relugolix, 95.4% vs leuprolide, 80.6%; amlodipine [n = 229]: 97.2% vs 85.5%; metoprolol [n = 88]: 95.7% vs 86.9%; acetylsalicylic acid [n = 259]: 97.0% vs 92.1%; clopidogrel [n = 43]: 96.4% vs 86.7%; simvastatin [n = 78]: 98.0% vs 87.3%). Incidence and types of adverse events (AEs) among men who received these medications were mostly consistent with overall population results, with some increases in grade ≥ 3 and fatal AEs.
CONCLUSION
Relugolix suppressed testosterone and was generally well tolerated when given with concomitant CV agents.
TRIAL REGISTRATION
Clinical Trial ID NCT03085095.
PRIOR PRESENTATION
Data presented at 15th Annual Genitourinary Cancers Symposium; February 17-19, 2022, San Francisco, CA, USA [Abstract 101, Poster board E11]. The published abstract from this presentation can be found at https://ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.101 .
Topics: Male; Humans; Leuprolide; Antihypertensive Agents; Fibrinolytic Agents; Antineoplastic Agents, Hormonal; Prostatic Neoplasms; Testosterone; Gonadotropin-Releasing Hormone
PubMed: 37713020
DOI: 10.1007/s12325-023-02634-7