Chemotherapy最新文献

{"title":"Carnitine Levels Decrease during Oxaliplatin Infusion: A Pilot Study.","authors":"Lianne P W van Geffen, Floortje Mols, Veerle C M Geurts, Gerard Vreugdenhil","doi":"10.1159/000546614","DOIUrl":"10.1159/000546614","url":null,"abstract":"<p><p><p>Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of chemotherapy. Low carnitine levels might negatively affect the development of CIPN. However, little is known of the course of carnitine levels during and directly after chemotherapy administration. Intervention studies using carnitine to prevent CIPN were contradictory, possibly due to different timing and route of carnitine supplementation. Better understanding of carnitine courses might improve future studies. This study aimed to investigate whether oxaliplatin-based chemotherapy administration affects blood and urinary levels of carnitine. We hypothesized that oxaliplatin increases renal excretion of carnitine, thereby causing a carnitine deficiency, which might contribute to the development of CIPN.</p><p><strong>Methods: </strong>Ten patients, starting their first cycle of oxaliplatin-based chemotherapy, were enrolled in this observational pilot study. Blood and urinary samples were taken before, during and after infusion of oxaliplatin. Primary endpoints were changes in plasma and urinary concentrations of free carnitine and carnitine esters during administration of oxaliplatin-based chemotherapy.</p><p><strong>Results: </strong>This study showed a significant decrease of both free carnitine and carnitine esters in plasma 2 h after the start of infusion of oxaliplatin-based chemotherapy. Moreover, a non-significant increase in urine carnitine concentration was seen during the chemotherapy infusion.</p><p><strong>Conclusion: </strong>The altered plasma and urinary concentrations of carnitine support our hypothesis that oxaliplatin causes increased renal excretion of carnitine, thereby lowering blood-carnitine levels and increasing urinary carnitine levels. With continued loss of carnitine over several chemotherapy cycles, this may result in the development of carnitine deficiency, which could contribute to the development of CIPN. These preliminary results provide a basis for hypothesis generation; larger longitudinal studies are required to confirm these findings and to determine the clinical relevance. </p>.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"153-162"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Insights into Epiploic Appendagitis in a Breast Cancer Patient on Abemaciclib: A Case Report.","authors":"Juned Islam, Peta Hughes, Fiona Lam, Karen DeSouza","doi":"10.1159/000548495","DOIUrl":"10.1159/000548495","url":null,"abstract":"<p><strong>Introduction: </strong>Epiploic appendagitis is an uncommon cause of acute abdominal pain, often mimicking surgical emergencies. This case highlights the diagnostic process for epiploic appendagitis in a breast cancer patient receiving abemaciclib, a CDK4/6 (cyclin-dependent kinase) inhibitor, and discusses potential associations with targeted therapies.</p><p><strong>Case presentation: </strong>We present a case of a 48-year-old female on adjuvant abemaciclib for stage IIIA breast cancer who developed acute left iliac fossa pain. Clinical assessment, laboratory investigations, transvaginal ultrasound, and subsequent computed tomography (CT) imaging of the abdomen and pelvis were performed to establish the diagnosis. CT imaging revealed a characteristic ovoid fat-density lesion with surrounding inflammation adjacent to the sigmoid colon, consistent with epiploic appendagitis. Other differential diagnoses, including ovarian pathology and diverticulitis, were excluded. The patient was managed conservatively with analgesia, and the abemaciclib was temporarily discontinued and restarted at a lower dose, leading to symptom resolution. This case underscores the importance of considering epiploic appendagitis in the differential diagnosis of acute abdominal pain, particularly in patients on targeted therapies like abemaciclib, which are known to have gastrointestinal side effects. Timely and accurate diagnosis via imaging avoided unnecessary surgical intervention.</p><p><strong>Conclusion: </strong>This case is the first of its kind to propose a novel association between the use of targeted therapies such as abemaciclib and the development of inflammatory conditions such as epiploic appendagitis. It emphasises the crucial role of clinical suspicion and appropriate imaging in establishing this rare diagnosis. Further research is warranted to explore potential links between CDK4/6 inhibitors and the development of epiploic appendagitis.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"200-204"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12668706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Pegfilgrastim in Japanese Patients with Advanced or Metastatic Urothelial Carcinoma.","authors":"Takahiro Harano, Masaomi Ikeda, Shuhei Hirano, Soichiro Shimura, Masayoshi Toyoda, Satoshi Okuda, Dai Koguchi, Hideyasu Tsumura, Daisuke Ishii, Kazumasa Matsumoto","doi":"10.1159/000543333","DOIUrl":"10.1159/000543333","url":null,"abstract":"<p><strong>Introduction: </strong>Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) therapy is indicated as first-line or neoadjuvant chemotherapy (NAC) for patients with advanced or metastatic urothelial carcinoma (UC). However, no studies reported ddMVAC therapy with pegfilgrastim (3.6 mg) in Japanese patients. We investigated the safety and efficacy of ddMVAC therapy with pegfilgrastim in patients with advanced or metastatic UC.</p><p><strong>Methods: </strong>A total of 43 patients received ddMVAC therapy with pegfilgrastim (3.6 mg) from February 2021 to December 2023. Among them, 25 and 18 patients received this regimen as first-line chemotherapy and NAC, respectively. We assessed toxicity and efficacy using Common Terminology Criteria for Adverse Events version 4.0 and Response Evaluation Criteria in Solid Tumors version 1.1, respectively.</p><p><strong>Results: </strong>The median number of ddMVAC therapy cycles was 3 (range: 1-5), with a total of 131 cycles. Cisplatin at the full dose without reduction was administered to 24 (56%) patients. Grade ≥3 hematologic toxicity occurred in 15 (35%) patients. Among them, anemia, neutropenia, thrombocytopenia, and febrile neutropenia were 13.9%, 9.3%, 11.7%, and 7.0%, respectively. Regarding non-hematologic toxicity, grade 3 appetite loss was observed in 2 (5%) patients. Complete response was observed in 7 (16%) patients and partial response in 26 patients (60%), yielding an objective response rate of 76%. Pathologic complete response (pCR; ypT0pN0) was observed in 3 (16.7%) patients and downstaging occurred in 13 (72.2%) patients. The median progression-free survival and overall survival of first-line treatment with ddMVAC were 18.6 months and not reached, respectively.</p><p><strong>Conclusion: </strong>The ddMVAC with pegfilgrastim (3.6 mg) reduced injection-related patient burden, caused fewer grade ≥3 adverse events, and demonstrated similar efficacy when compared to the original ddMVAC regimen that used granulocyte colony-stimulating factor for 7 consecutive days.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"85-91"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-Kill Curve Analysis of Fucoidan Combination with Conventional Antibiotics against Biofilms Formation of Methicillin-Resistant Staphylococcus aureus and Acinetobacter baumannii Clinical Isolates.","authors":"Mohsen Nazari, Mohammad Taheri, Fatemeh Nouri, Maryam Bahmanzadeh, Mohammad Yousef Alikhani","doi":"10.1159/000542826","DOIUrl":"10.1159/000542826","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigates the efficacy of fucoidan combination with antibiotics, against single-species biofilms and mixed-species, individual planktonic, and coculture planktonic conditions of Methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii by time-kill curve analysis.</p><p><strong>Materials and methods: </strong>Fucoidan, a sulfated polysaccharide, was purchased from Sigma-Aldrich, USA. Clinical isolates of MRSA and A. baumannii from diabetic foot ulcers (DFUs) were used, and single-species biofilms and mixed-species biofilms were developed to assess susceptibility to the treatments using MIC, MBC, minimum biofilm inhibitory concentration, minimum biofilm eradication concentration, and time-kill kinetics assays. Cytotoxicity was assessed using MTT assays on human skin fibroblast cells (HSF-PI 16).</p><p><strong>Results: </strong>The study determined the geometric mean MIC and MBC values for gentamicin, imipenem, and fucoidan in MRSA and A. baumannii cultures, both individually and in co-cultures. The MIC and MBC values were significantly lower under co-culture conditions, indicating enhanced antimicrobial efficacy. Synergy between fucoidan, gentamicin, and imipenem was confirmed through time-kill assays, which showed complete inhibition of bacterial growth and effective biofilm eradication, particularly in mixed-species biofilms. Fucoidan demonstrated low cytotoxicity at optimal concentrations, highlighting their potential as a therapeutic strategy against biofilm-associated infections in DFUs.</p><p><strong>Conclusion: </strong>The study concludes that fucoidan, in combination with gentamicin and imipenem, effectively disrupts mixed-species biofilms of MRSA and A. baumannii, suggesting fucoidan-based therapies could improve outcomes for DFU patients, warranting further clinical investigation.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"53-64"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779260","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":"Predicting Reprisal of Solid Cancer Treatment and 60-Month Survival after Medical Intensive Care: A Single-Centre Cohort Study.","authors":"Victoria Ferrari, Lucas Morand, Hervé Hyvernat, Renaud Schiappa, Jean Dellamonica, Nihal Martis","doi":"10.1159/000542101","DOIUrl":"10.1159/000542101","url":null,"abstract":"<p><strong>Introduction: </strong>Our study aimed to identify relevant features associated with the reprisal of antineoplastic treatment in patients with solid cancers after unplanned admittance to the intensive care unit (ICU) and to assess 60th-month survival in patients with solid neoplasms admitted to the ICU.</p><p><strong>Methods: </strong>This single-centre retrospective study of critically ill patients with active cancers was performed over a 13-year period (2005-2018). Patients' characteristics, overall survival, and antineoplastic treatment reprisal were extracted from digital medical files and compared.</p><p><strong>Results: </strong>134 patients were included in the study. Solid neoplasms were mostly localised to the head and neck (n = 53) followed by lung cancers (n = 29). Sepsis was the leading cause of ICU admission (62.1%) with 41/82 patients presenting with septic shock. Antineoplastic treatments were resumed in 40 patients. An age ≤60 years and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1 were found to be predictors for treatment reprisal, with odd ratios of, respectively, 2.83 (95% CI, 1.15-6.99) and 5.45 (95% CI, 2.01-14.82); area under the ROC curve of 72% (95% CI, 63-81%). Survival after the immediate discharge from the ICU was 101/134 (75%) and the 60-month survival rate was 29% and significantly higher in the treatment-reprisal group.</p><p><strong>Conclusions: </strong>Age and ECOG PS were found to be predictors for treatment reprisal in patients with solid neoplasms admitted to the ICU. The latter benefits from better long-term survival.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"65-73"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616059","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":"Meta-Analysis of the Efficacy and Safety of Pembrolizumab in the Treatment of Advanced Gastric Cancer and Gastroesophageal Junction Cancer.","authors":"Jingyun Yang, Weisheng Luo, Xiaocong Ma, Yinhang Cui, Jiacheng Xie, Chengzhen Pan, Ziyao Chen, Shuang Yang","doi":"10.1159/000540071","DOIUrl":"10.1159/000540071","url":null,"abstract":"<p><strong>Introduction: </strong>Pembrolizumab has been approved for the first-line treatment of patients with advanced gastric cancer (GC) and gastroesophageal junction (GEJ) cancer. However, the results of several clinical trials are not entirely consistent, and the dominant population of first-line immunotherapy for advanced GC/GEJ still needs to be precisely determined.</p><p><strong>Purpose: </strong>The aim of this meta-analysis was to assess the efficacy and safety of pembrolizumab in the treatment of advanced GC/GEJ.</p><p><strong>Methods: </strong>We conducted computerized searches across multiple databases, including PubMed, Cochrane Library, Web of Science, and Embase. We established the inclusion criteria to comprise randomized clinical trials examining the efficacy of pembrolizumab in late-stage GC/GCJ cancer. We conducted a meta-analysis of outcome measures using STATA 14.0 software.</p><p><strong>Results: </strong>A total of six studies involving 1,448 cases were included in this analysis. The results of the meta-analysis indicate that, when compared to chemotherapy, patients in the pembrolizumab group experienced a significant reduction in the risk of mortality in terms of overall survival (OS) (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.65-0.79, p < 0.01). In terms of progression-free survival (PFS), pembrolizumab was associated with a similar PFS as compared to chemotherapy (HR = 0.88, 95% CI: 0.73-1.07, p = 0.206). Subgroup analyses based on PD-L1 expression levels indicated a significantly longer PFS with pembrolizumab in subgroups of patients with PD-L1 CPS ≥10 but not in those with PD-L1 CPS ≥1 and PD-L1 CPS ≥5. Subgroup analyses based on distinct geographical regions revealed a comparable effect of PFS in patients residing in Asia or the USA Subgroup analysis based on tumor sites consistently demonstrated a similar effect of PFS in patients with EC/GEJ tumors and GC patients.</p><p><strong>Conclusion: </strong>Our findings demonstrated that pembrolizumab led to a significant extension in OS and objective response rate, along with a favorable tolerability profile compared to chemotherapy. Furthermore, the observed survival benefits were particularly pronounced in subgroup patients with a CPS of ≥10. Given the potential limitations inherent in our study, it is imperative to underscore the necessity for further large-scale RCTs to corroborate our results.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"37-52"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554272","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":"Aerobic Exercise Alleviates Doxorubicin-Induced Cardiotoxicity via Inhibition of Ferroptosis.","authors":"Haiyun Liu, Hongmei Li, Nihong Zhou, Yimin Zhang, Lijing Gong, Enming Zhang, Yimin Zhang","doi":"10.1159/000546096","DOIUrl":"10.1159/000546096","url":null,"abstract":"<p><strong>Introduction: </strong>Doxorubicin (DOX), a potent anthracycline, is widely used in cancer therapy, but its effect is limited by doxorubicin-induced cardiotoxicity (DIC). Increasing evidence suggests that DIC is associated with ferroptosis, a cell death characterized by the iron-dependent accumulation of lipid peroxides. Although aerobic exercise is recommended for chemotherapy-related cardiac dysfunction, the extent to which its protective effects against DIC are mediated through the inhibition of ferroptosis remains largely unclear. The aim of this study was to elucidate the mechanism through which aerobic exercise attenuates DIC and provide theoretical support for promoting scientifically guided exercise in patients with DIC.</p><p><strong>Methods: </strong>We conducted in vivo experiments involving 8 weeks of aerobic exercise during and after DOX treatment of C57BL/6J male mice, and in vitro experiments, H9c2 cells were treated with DOX and ferrostatin-1 (Fer-1, a ferroptosis inhibitor). Mice were randomly assigned into four groups: Control (C, n = 6), DOX (D, n = 10), aerobic exercise (E, n = 6) and DOX + aerobic exercise (DE, n = 10). Echocardiography was used to measure left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) to assess cardiac function in mice. ELISA kits were used to quantify serum biomarkers of myocardial injury, including cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), and lipid peroxidation markers, such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). Hematoxylin and eosin and Masson's trichrome were performed to evaluate myocardial structural damage. Fluorescent probes were used to detect ferrous iron (Fe2+), reactive oxygen species (ROS), and lipid peroxides in H9c2 cells. Western blotting was conducted to analyze ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), acyl-CoA synthetase long-chain family member 4 (ACSL4), transferrin receptor 1 (TfR1), and ferritin heavy chain 1 (FTH1).</p><p><strong>Results: </strong>DOX treatment significantly induced cardiac damage and dysfunction, as evidenced by disrupted myocardial tissue, increased myocardial fibrosis and cTnT levels, and decreased LVEF and LVFS. However, aerobic exercise effectively reduced cardiac structural and functional damage, and improved the rate of survival in mice. Furthermore, DOX-induced ferroptosis in cardiomyocytes both in vitro and in vivo, as marked by increased levels of Fe2+, ROS, and MDA, along with altered protein expression, including reduced FTH1 and SLC7A11 levels and increased ACSL4 levels. In contrast, aerobic exercise significantly mitigated these changes in vivo, and Fer-1 also effectively inhibited these effects in vitro.</p><p><strong>Conclusion: </strong>Collectively, this study demonstrates that aerobic exercise alleviates DIC via the inhibition of ferroptosis.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"137-152"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986663","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":"The Impacts of Active and Inactive Ghrelin on Cachexia and Immune Checkpoint Inhibitor Monotherapy in Patients with Non-Small Cell Lung Cancer.","authors":"Daiki Murata, Koichi Azuma, Yuuya Nishii, Kenta Murotani, Goushi Matama, Akihiko Kawahara, Takaaki Tokito, Tetsuro Sasada, Tomoaki Hoshino, Koichi Azuma","doi":"10.1159/000543425","DOIUrl":"10.1159/000543425","url":null,"abstract":"<p><strong>Introduction: </strong>Identifying the underlying mechanisms of immune checkpoint inhibitor resistance in patients with cachexia is a current challenge. Ghrelin is a peptide hormone that plays an important role in the metabolism of patients with cancer cachexia. Despite the importance of ghrelin in cancer cachexia, most previous studies on the subject have not distinguished between the forms of ghrelin.</p><p><strong>Methods: </strong>We retrospectively screened patients with advanced or recurrent non-small cell lung cancer receiving PD-1/PD-L1 inhibitor monotherapy. Active and inactive ghrelin levels were measured in 100 patients with available plasma samples at immune checkpoint inhibitor initiation. Cancer cachexia was defined as weight loss of at least 5% during the past 6 months or weight loss of at least 2% with a BMI <20. We analyzed the associations of the active and inactive ghrelin levels and active-to-inactive ghrelin ratio (AIR) with cancer cachexia. The prognostic impact of the active and inactive ghrelin levels and AIR were also analyzed.</p><p><strong>Results: </strong>Among 100 patients, 35 were diagnosed with cancer cachexia. The active ghrelin level and AIR were significantly associated with cancer cachexia, whereas the inactive ghrelin level was not. The active and inactive ghrelin levels and AIR were not associated with patient prognosis.</p><p><strong>Conclusion: </strong>The active ghrelin level and AIR were associated with cancer cachexia but not with patient prognosis. The function of the active and inactive forms of ghrelin may differ in cancer patients. The form of ghrelin should be clearly mentioned in relevant studies on cancer cachexia.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"119-125"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022452","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":"Acknowledgement to Reviewers.","authors":"","doi":"10.1159/000549024","DOIUrl":"10.1159/000549024","url":null,"abstract":"","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"205-206"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488089","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":"Role of a Therapeutic Drug Monitoring-Guided Strategy of Isavuconazole for Optimizing Efficacy/Safety Outcomes in Onco-Hematological Pediatric Patients: A Systematic Review.","authors":"Milo Gatti, Pier Giorgio Cojutti, Federico Pea","doi":"10.1159/000547799","DOIUrl":"10.1159/000547799","url":null,"abstract":"<p><strong>Introduction: </strong>Evidence concerning the implementation of a therapeutic drug monitoring (TDM)-guided approach for optimizing isavuconazole exposure in onco-hematological pediatric patients is limited. The aim of this systematic review was to summarize the current evidence about the role that a TDM-guided strategy of isavuconazole may have in optimizing efficacy/safety outcomes of invasive fungal infection (IFI) treatment/prophylaxis among onco-hematological pediatric patients.</p><p><strong>Methods: </strong>Two authors independently searched the PubMed-MEDLINE and Scopus databases up to 25 April 2025, to retrieve randomized controlled trials or observational studies providing real-life data assessing isavuconazole exposure according to a TDM-guided approach in pediatric patients, and evaluating the relationship between isavuconazole exposure and efficacy/safety outcomes. Data were independently extracted by the two authors, and the quality of the included studies was independently assessed by means of the Cochrane Risk of Bias Tool (RoB 2.0) in case of randomized controlled trials, and by means of the Newcastle-Ottawa scale in case of observational studies and case series. Mortality attributable to IFI and hepatotoxicity occurrence were selected as primary outcomes. Descriptive statistics were used for summarizing the retrieved data.</p><p><strong>Results: </strong>After screening 577 articles, eight studies were included in the systematic review (five retrospective observational cohort studies and 3 case series; n = 116). Attainment of optimal isavuconazole exposure at first TDM assessment ranged from 36.7% to 83.3% of included patients, being underexposure reported in up to 40.0% of cases. Overall, mortality attributable to IFI occurred in 10 out of 59 patients (16.9%) in which this outcome was evaluated, being associated with isavuconazole underexposure only in 30.0% of cases. Hepatotoxicity occurred in 14 out of 78 included patients (17.9%), being related to isavuconazole overexposure in 50.0% of cases.</p><p><strong>Conclusion: </strong>Despite limited findings, our systematic review may support a potential role for a TDM-guided strategy in optimizing isavuconazole exposure among onco-hematological pediatric patients, particularly considering both the non-negligible proportion of cases who failed in attaining optimal exposure with standard dosing regimens.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":" ","pages":"163-176"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788385","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}