Chemotherapy最新文献

{"title":"Erratum.","authors":"","doi":"10.1159/000529827","DOIUrl":"https://doi.org/10.1159/000529827","url":null,"abstract":"","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"1"},"PeriodicalIF":3.3,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment with Brivudine in Immunocompromised Pediatric Patients with Herpes Zoster.","authors":"Clara Vogel, Laura Wetzel, Peter Wutzler, Bernd Gruhn","doi":"10.1159/000531034","DOIUrl":"10.1159/000531034","url":null,"abstract":"<p><strong>Introduction: </strong>Herpes zoster (HZ) is caused by endogenous reactivation of latent varicella-zoster virus (VZV) that persists in sensory ganglia after primary infection. The incidence and severity of HZ increase during immunosuppression. Especially, immunocompromised patients are at high risk of developing a cutaneous rash and suffering from delayed healing of lesions. Bromovinyl deoxyuridine (brivudine), one of the most potent oral inhibitors of VZV replication, is widely used in the therapy of HZ in adult patients, particularly in Europe. In this study, we investigated the efficacy of brivudine in immunocompromised children to provide an outpatient treatment option.</p><p><strong>Methods: </strong>In this retrospective study, we included 64 immunocompromised pediatric patients with a median age of 14 years. Forty-seven patients received immunosuppressive therapy as part of hematopoietic stem cell transplantation and 17 patients as part of chemotherapy. Primary diagnosis was made clinically by examining the nature and the localization of the skin lesions. Laboratory confirmation was conducted based on the detection of VZV DNA in vesicle fluid and blood samples. Brivudine was administered orally at a single dose of 2 mg/kg per day. We monitored the patients' response for the full time of treatment and observed the time of full crusting of lesions, loss of crusts, and any adverse effects that occurred.</p><p><strong>Results: </strong>Patients received medication for 7-21 days (median: 14 days). All children responded promptly to antiviral treatment and recovered completely from their HZ infections without complications. Crusting of lesions was reached after 3-14 days (median: 6 days). Full healing of skin lesions was ascertained within 7-21 days (median: 12 days). Overall, brivudine therapy was well tolerated. No clinical side effects during or after the treatment were observed. High compliance was achieved due to the once-daily dosing regimen. All patients were treated in an outpatient manner.</p><p><strong>Conclusion: </strong>Oral brivudine was a very effective and well-tolerated therapy in immunocompromised children with HZ infection. The oral administration offers the potential for outpatient treatment of HZ in these patients.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"222-227"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9524160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Targeted Drugs for Acute Myeloid Leukemia and Antifungals: Pharmacokinetic Challenges and Opportunities.","authors":"Emanuela Salvatorelli,&nbsp;Giorgio Minotti,&nbsp;Pierantonio Menna","doi":"10.1159/000530447","DOIUrl":"https://doi.org/10.1159/000530447","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a life-threatening disease whose treatment is made difficult by a number of mutations or receptor overexpression in the proliferating cellular clones. Life expectancy of patients diagnosed with new, relapsed-refractory, or secondary AML has been improved by drugs targeted at such moieties. Regrettably, however, clinical use of new AML drugs is complicated by pharmacokinetic interactions with other drugs the patient is exposed to.</p><p><strong>Summary: </strong>The most relevant drug-drug interactions (DDI) with clinical implications build on competition for or induction/inhibition of CYP3A4, which is a versatile metabolizer of a plethora of pharmacological agents. Here, we review DDI between AML drugs and the agents used to prevent or treat invasive fungal infections (IFI). The pathophysiology of AML, characterized by functionally defective white blood cells and neutropenic/immunosuppressive effects of concomitant induction chemotherapy, can in fact increase the risk of infectious complications, with IFI causing high rates of morbidity and mortality. Triazole antifungals, such as posaconazole, are strong inhibitors of CYP3A4 and may thus cause patient's overexposure to AML drugs that are metabolized by CYP3A4. We describe potential strategies to minimize the consequences of DDI between triazole antifungals and targeted therapies for AML and the role that collaboration between clinical pharmacologists, hematologists, and clinical or laboratory microbiologists may have in these settings.</p><p><strong>Key messages: </strong>Therapeutic drug monitoring and clinical pharmacology stewardship could represent two strategies that best express multidisciplinary collaboration for improving patient management.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 3","pages":"170-182"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety Signal between Azacitidine and Pericarditis.","authors":"Brandon Chu,&nbsp;Ajit Venkatakrishnan,&nbsp;Pushkar Aggarwal","doi":"10.1159/000526610","DOIUrl":"https://doi.org/10.1159/000526610","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced pericarditis is an important cause of pericarditis and if unnoticed and unmanaged can lead to constrictive pericarditis, pericardial effusion, and cardiac tamponade.</p><p><strong>Objective: </strong>The objective of this analysis was to determine if a significant signal exists between azacitidine use and pericarditis.</p><p><strong>Methods: </strong>A pharmacovigilance analysis was performed using the FDA Adverse Event Database.</p><p><strong>Results: </strong>48 reports of azacitidine-induced pericarditis with azacitidine as the suspect drug were identified. The most common indications for azacitidine use in the adverse event reports were myelodysplastic syndrome (48%) and acute myelogenous leukemia (27%). Physicians reported 44% of the azacitidine-induced pericarditis reports, while other health professional reported 52% of the reports. The disproportionality analysis showed a proportional reporting ratio of 5.0, χ2 of 149.8, reporting odds ratio of 5.0, and IC025 of 1.8. Literature review found 3 case reports of azacitidine-induced pericarditis.</p><p><strong>Conclusion: </strong>The signal between azacitidine and pericarditis was found to be statistically significant. Clinicians should be aware of the possible risk of pericarditis when prescribing azacitidine. If there is suspicion for azacitidine-induced pericarditis, clinicians should consider discontinuation of azacitidine to improve patient's symptoms and reduce the likelihood of the development of constrictive pericarditis, pericardial effusion, and cardiac tamponade.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 2","pages":"115-118"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9581211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution.","authors":"Joanna Drozd-Sokolowska,&nbsp;Krzysztof Mądry,&nbsp;Joanna Barankiewicz,&nbsp;Katarzyna Kobylińska,&nbsp;Przemysław Biecek,&nbsp;Jagoda Rytel,&nbsp;Ewa Karakulska-Prystupiuk,&nbsp;Kamila Skwierawska,&nbsp;Aleksander Salomon-Perzyński,&nbsp;Tomasz Stokłosa,&nbsp;Grzegorz Władysław Basak","doi":"10.1159/000527010","DOIUrl":"https://doi.org/10.1159/000527010","url":null,"abstract":"<p><strong>Introduction: </strong>Venetoclax combined with azacitidine (AZA-VEN) constitutes an option for the treatment of acute myeloid leukemia. There are, however, no data on the COVID-19 incidence and outcome in patients treated with AZA-VEN.</p><p><strong>Methods: </strong>Patients with acute leukemia treated with AZA-VEN at a single institution were included in this prospective observational study.</p><p><strong>Results: </strong>Thirteen patients were enrolled, 46% with treatment-naïve, and 56% with relapsed/refractory disease. Fifty-four percent of patients were males; the median age was 69 years. Six patients (46%) developed COVID-19 during the observation time. The median time to COVID-19 was 24 days from the initiation of AZA-VEN. The 2-month cumulative incidence of COVID-19 was 46.2%. Two patients (33%) succumbed to COVID-19. The 100-day COVID-19-free survival from AZA-VEN initiation was 61%. The median follow-up time was 4.3 months.</p><p><strong>Discussion/conclusion: </strong>COVID-19 constitutes a frequent complication of AZA-VEN treatment in the era of the COVID-19 pandemic, leading to death in a significant proportion of patients.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 1","pages":"16-22"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10598534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endobronchial Presentation of Hodgkin Lymphoma Responding to Pembrolizumab: A Case Report.","authors":"Marianna Gentilini, Beatrice Casadei, Alice Morigi, Ginevra Lolli, Marco Ferrari, Matteo Carella, Lisa Argnani, Pier Luigi Zinzani","doi":"10.1159/000527059","DOIUrl":"10.1159/000527059","url":null,"abstract":"<p><p>An endobronchial localization of Hodgkin lymphoma is rare, and few experiences since the 1900s have been reported in the literature. Here we report the first case of a relapsed/refractory Hodgkin lymphoma with a critical vegetative mass at the level of the trachea successfully treated with pembrolizumab.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"219-221"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9627346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ceramide Analog 5cc Overcomes TRAIL Resistance by Enhancing JNK Activation and Repressing XIAP Expression in Metastatic Colon Cancer Cells.","authors":"Qiqian Huang, Feiyan Liu","doi":"10.1159/000531757","DOIUrl":"10.1159/000531757","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to be an effective apoptosis inducer due to its selectivity for tumor cells. However, many cancer cells, especially metastatic cancer cells, often exhibit resistance to TRAIL because their apoptotic pathway is impaired or their pro-survival pathway is overactivated. TRAIL resistance is the main obstacle to current TRAIL therapy. Nowadays, ceramide analogs represent a new class of potential anticancer agents. Therefore, we hypothesized that disrupting pro-survival signaling with ceramide analogs would increase TRAIL-mediated apoptosis.</p><p><strong>Methods: </strong>MTT assay and flow cytometry were conducted to evaluate the synergistic effect of ceramide analog 5cc on TRAIL in metastatic colon cancer cells. Western blot was used to detect signaling proteins affected by 5cc. RNA interference was performed to analyze the effects of specific gene on 5cc-enhanced apoptosis.</p><p><strong>Results: </strong>Ceramide analog 5cc markedly enhanced TRAIL-induced apoptosis evidenced by increased propidium iodide/annexin V double-positive cells and PARP cleavage in SW620 and LS411N cells. At the molecular level, 5cc significantly reduced the expression of anti-apoptotic protein X-linked inhibitor of apoptosis protein (XIAP) through the activation of the c-Jun n-terminal kinase (JNK) pathway which is critically involved in sensitizing tumor cells to TRAIL/5cc combination. JNK-silenced cells exhibited a significant reversal of TRAIL/5cc-mediated apoptosis.</p><p><strong>Conclusion: </strong>Our data demonstrated that ceramide analog 5cc overcomes TRAIL resistance by enhancing JNK activation and repressing XIAP expression in metastatic colon cancer cells.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"210-218"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIC Discrepancies between Parenteral and Oral Anti-Staphylococcal Beta-Lactams among MSSA.","authors":"Brandy N Hernandez,&nbsp;Thomas Dilworth,&nbsp;Jacob Kesner,&nbsp;Keenan Ryan,&nbsp;Haedi Thelen,&nbsp;Renée-Claude Mercier","doi":"10.1159/000526630","DOIUrl":"https://doi.org/10.1159/000526630","url":null,"abstract":"<p><strong>Introduction: </strong>Recent evidence has shown that oral antibiotic therapy is not inferior to IV antibiotic therapy in the treatment of complicated Staphylococcus aureus infections. Therefore, oral antibiotic therapy is now frequently prescribed in clinical practice due to cost benefit, ease of administration, decreased complication rate, and lack of need for IV access. In vitro susceptibility testing for β-lactam oral antibiotics is not routinely performed as the guidelines provided by the Clinical and Laboratory Standards Institute (CLSI) recommend using oxacillin and cefoxitin as surrogate markers. Hence, oral antibiotic susceptibilities for cephalexin and dicloxacillin are not reported and implied based on oxacillin and cefoxitin. The objective of the current study was to determine whether susceptibilities among S. aureus isolates are predictable when comparing commonly used IV and oral beta-lactams.</p><p><strong>Methods: </strong>Cefazolin, cephalexin, dicloxacillin, and oxacillin broth microdilution minimum inhibitory concentrations (MICs) were determined for 100 clinical isolates of methicillin-sensitive S. aureus by broth microdilution following CLSI guidelines.</p><p><strong>Results: </strong>Among these isolates, median MICs for cephalexin were eight-fold higher than cefazolin MICs and median MICs for dicloxacillin were four-fold less than oxacillin MICs. Ten percent of more strains studied had a major or very major error in its susceptibility reporting when cephalexin was compared to its surrogate marker oxacillin.</p><p><strong>Discussions/conclusions: </strong>The variations in MICs observed compounded with the dosing and pharmacokinetic differences of oral versus IV β-lactam suggests that establishing breakpoints for oral β-lactam antibiotics is necessary to ensure adequate therapy is selected for the treatment of complex S. aureus infections.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 1","pages":"55-60"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9149683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Therapy of Non-Small Cell Lung Cancer and Liver Cancer: Functional Nanocarriers for the Delivery of Cisplatin and Tissue Factor Pathway Inhibitor-2.","authors":"MingZhong Ma,&nbsp;JianWei He,&nbsp;Bo Gao,&nbsp;JianXun Cao,&nbsp;DaMing Li,&nbsp;YongChun Li,&nbsp;Gang Huang,&nbsp;Xing Zhou","doi":"10.1159/000527536","DOIUrl":"https://doi.org/10.1159/000527536","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to construct folic acid-modified PEGylated paramagnetic nanoparticles (MNPs) co-carrying tissue factor pathway inhibitor-2 (TFPI-2) and cisplatin (CDDP), and to study the molecular-targeting and inhibitory effects of the nanocomposite on non-small cell lung cancer (NSCLC) and liver cancer.</p><p><strong>Methods: </strong>Nanocomposites were prepared using amino-modified iron oxide nanoparticles as carriers, co-loading CDDP and PEGylated FA/TFPI-2. Transmission electron microscopy, UV absorption spectrum, and dynamic light scattering were employed to characterize the morphology, structure, particle size, and zeta potential of the nanocomposite. The phenylenediamine method was used to detect the loading of CDDP, and the CCK-8 assay was used to detect the toxic effect of the nanocomposite on HUVECs, A549, and NCI-H460 cells. In tumor-bearing mice models, the antitumor effects of the nanocomposites were assessed using TUNEL staining (at the molecular level), reverse transcriptase quantitative polymerase chain reaction (at the gene level), hematoxylin and eosin staining (at the cellular level), and the appearance of the mice models.</p><p><strong>Results: </strong>The synthesized FA-MNP/CDDP/TFPI-2 nanocomposite was uniformly dispersed and spherical in shape (approximate diameter: 10 nm). The zeta potential of particles was -9.44 mV, and the average particle size was 25 nm. The loading amount of CDDP was 70.24 μg/mL (23.33%). The nanocomposite was nontoxic to HUVECs, while it showed a favorable inhibitory effect on A549 and NCI-H460 cells. In vivo experiments in mice demonstrated satisfactory imaging properties and therapeutic effects of nanocomposite against liver cancer.</p><p><strong>Discussion: </strong>FA-MNP/CDDP/TFPI-2 may provide insights for the development of new chemotherapeutic drugs.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 2","pages":"73-86"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9936126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Immune-Related Pneumonitis with PD-1/PD-L1 Inhibitors in Different Cancer Types and Treatment Regimens: A Systematic Review and Meta-Analysis of 22 Randomized Controlled Trials.","authors":"Lei Han,&nbsp;Guangxin Li,&nbsp;Huihui Li,&nbsp;Lei Zhao","doi":"10.1159/000523904","DOIUrl":"https://doi.org/10.1159/000523904","url":null,"abstract":"<p><strong>Background: </strong>Pneumonitis, the specific toxicity associated with PD-1/PD-L1 inhibitors, is severe and potentially life-threatening, and its incidence and severity are poorly understood among different tumor types or treatment methods. This meta-analysis was performed to compare the incidence and severity of pneumonitis among different tumor types and treatment regimens.</p><p><strong>Methods: </strong>MEDLINE and Embase were retrieved until September 2021. Meta-analysis of the risk of pneumonitis was calculated using a fixed-effect model. Pooled analysis of the incidence of pneumonitis in different tumor types was performed using a metaprop function.</p><p><strong>Results: </strong>Twenty two randomized controlled trials (RCTs) (n = 10,700) were included for pool analysis, and eighteen RCTs (n = 8,852) were eligible for meta-analysis. For all-grade pneumonitis, the risk of the combination therapy (PD-1/PD-L1 plus CTLA-4 inhibitor) was 3.62 times significantly higher than that of monotherapy, and 4.06 and 1.78 times significantly higher than that of chemotherapy and placebo than monotherapy. The incidence of pneumonitis was not significantly different between PD-1/PD-L1 inhibitor versus ipilimumab or between low doses versus high doses. For high-grade (grade ≥3) pneumonitis, the risk in PD-1/PD-L1 inhibitors alone was 3.62 times significantly higher than chemotherapy. No significant difference was found in the incidence of pneumonitis between combination versus monotherapy, monotherapy versus placebo, combination versus ipilimumab alone, monotherapy versus ipilimumab alone, or low doses versus high doses.</p><p><strong>Conclusions: </strong>Compared with chemotherapy, PD-1/PD-L1 inhibitor monotherapy may cause more treatment-related pneumonitis. Increasing the dose of PD-1/PD-L1 inhibitor does not significantly increase the incidence of pneumonitis. Compared with the monotherapy, combination therapy does not increase the incidence of pneumonitis significantly.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":"68 1","pages":"1-15"},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10652279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}