Drug Design, Development and Therapy最新文献

{"title":"Cordycepin Ameliorates Renal Interstitial Fibrosis by Inhibiting Drp1-Mediated Mitochondrial Fission.","authors":"Yingxue Sun, Shi Jin, Jun Chen, Jian Zhang, Yufei Lu, Qiuyu Gu, Zhixin Yan, Weize Chen, Annan Chen, Yi Fang, Wenye Geng, Xialian Xu, Nana Song","doi":"10.2147/DDDT.S498525","DOIUrl":"https://doi.org/10.2147/DDDT.S498525","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the mechanisms and specific targets of cordycepin in the treatment of renal fibrosis using a unilateral ischemia-reperfusion (UIR) model.</p><p><strong>Methods: </strong>A UIR mouse model was established, followed by intraperitoneal injections of cordycepin and Mdivi-1. Masson's trichrome staining and PAS staining were used to identify renal tubulointerstitial fibrosis and assess the degree of renal injury. Fibrosis markers and mitochondrial dynamics-related proteins were evaluated using Western blotting, while differential gene expression and pathway enrichment were analyzed by RNA-seq. Molecular docking, molecular dynamics simulations and surface plasmon resonance were conducted to validate the specific binding sites of cordycepin on the target protein Drp1. Immunofluorescence and in vitro experiments further elucidated the therapeutic mechanism of cordycepin.</p><p><strong>Results: </strong>In vivo experiments showed that intraperitoneal injection of cordycepin significantly reduced renal inflammation and fibrosis, lowered serum creatinine levels, and decreased collagen deposition. Transcriptome analysis revealed that cordycepin treatment downregulated the mitochondrial fission pathway and upregulated the mitochondrial fusion pathway. Western blotting showed reduced levels of fibrosis markers α-SMA and FN, as well as downregulation of Drp1, MFF, and Fis1, and upregulation of OPA1 and Mfn2. In vitro, cordycepin inhibited TGF-β-induced injury in NRK-52E cells, reducing Drp1 expression and IL-6 secretion. Crosstalk experiments confirmed that decreased IL-6 levels were crucial for cordycepin anti-fibrotic effects by suppressing fibroblast activation.</p><p><strong>Conclusion: </strong>Cordycepin ameliorates renal fibrosis by targeting Drp1 to inhibit mitochondrial fission in injured renal tubular epithelial cells, reducing IL-6 secretion and inhibiting fibroblast activation.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1271-1287"},"PeriodicalIF":4.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Intravenous Dexmedetomidine Premedication on Sufentanil Median Effective Concentration During Tracheal Intubation in Obese Patients: A Randomized Controlled Study.","authors":"Qi Zeng, Jinjie Li, Yanrong Liu, Yiran Zhang, Hang Su, Faping Tu","doi":"10.2147/DDDT.S491599","DOIUrl":"https://doi.org/10.2147/DDDT.S491599","url":null,"abstract":"<p><strong>Purpose: </strong>Sufentanil is a potent opioid analgesic frequently used to suppress the tracheal intubation response. The pathophysiological changes of obesity may affect opioid pharmacokinetics and increase the risk of opioid-induced adverse effects. Dexmedetomidine as an adjunct to anesthetic induction could save the dosage of sufentanil and attenuate hemodynamic response to tracheal intubation. This study was aimed at investigating the effect of intravenous dexmedetomidine premedication on the median effective concentration (EC50) of sufentanil for tracheal intubation in obese patients.</p><p><strong>Patients and methods: </strong>Fifty obese patients undergoing elective bariatric or non-bariatric surgery under general anesthesia with tracheal intubation were equally randomized into the dexmedetomidine group and the saline group. Depending on the group, the patients were intravenously premedicated with 1 μg/kg dexmedetomidine or saline before anesthesia induction. Anesthesia was induced with target-controlled infusion of propofol (at 3.5 μg/mL) and sufentanil. The effect-site concentration of sufentanil for the first patient in the two groups was set at 0.4 ng/mL. The concentration of sufentanil for the next patient was determined using Dixon's up-and-down sequential method with an interval of 0.05 ng/mL, according to the responses of the previous patient. Hemodynamic variables and sufentanil dose were recorded. The EC50 and 95% confidence interval (CI) of sufentanil were determined using probit regression analysis.</p><p><strong>Results: </strong>The EC50 of sufentanil and 95% CI were 0.25 (95% CI, 0.17-0.31) ng/mL in the dexmedetomidine group and 0.43 (95% CI, 0.34-0.46) ng/mL in the saline group (<i>P</i> < 0.05). The dosage of sufentanil was significantly lower in the former than in the latter. The hemodynamics were stable in both groups during the study.</p><p><strong>Conclusion: </strong>Intravenous premedication with 1 μg/kg dexmedetomidine significantly decreased the EC50 of sufentanil and sufentanil requirement for tracheal intubation in obese patients.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1323-1332"},"PeriodicalIF":4.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Reshapes Intestinal Microecology to Alleviate Microgravity Stress.","authors":"Yanli Wang, Tian Chen, Zhe Shi, Lijinchuan Dong, Mengting Li, Bo Peng, Qi Li, Ruile Pan, Shuiming Xiao, Qing Yang, Ning Jiang, Xinmin Liu, Qin Hu, Ying Chen","doi":"10.2147/DDDT.S486371","DOIUrl":"https://doi.org/10.2147/DDDT.S486371","url":null,"abstract":"<p><strong>Background: </strong>During medium- to long-duration spaceflights, real-time microgravity can increase the health risks of astronauts. In particular, the disruption of intestinal homeostasis is closely related to other health problems, and it is necessary to monitor related treatment strategies. Ginseng is a well-known Chinese herbal medicine often used to maintain health. Ginseng total saponins (GTSs), which are the bioactive components of ginseng, have been reported to regulate immune homeostasis, anti-inflammation, and anti-oxidation. This study focused on the regulation of GTSs in intestinal homeostasis imbalance caused by microgravity.</p><p><strong>Methods: </strong>A hindlimb suspension (HLS) rat model was established to evaluate the intestinal protective effects of GTSs. Differentially expressed genes (DEGs) were screened using RNA-Seq. RT-PCR was performed to further focus and verify these results. The gut microbiome composition was examined based on 16S rRNA gene amplicon sequencing, and the short-chain fatty acids produced were further analyzed.</p><p><strong>Results: </strong>We found that GTSs intervention effectively improved the intestinal injury caused by simulated weightlessness, including reducing the pathological damage, increasing the expression of tight junction proteins and reducing the levels of inflammatory factors. Moreover, GTSs treatment significantly restored the levels of intestinal immunity-related genes and remodeled the gut microbiota. In particular, GTSs significantly increased the abundance of short-chain fatty acid metabolism-related bacteria, thereby increasing the level of propionic acid, butyric acid, isobutyric acid.</p><p><strong>Conclusion: </strong>Our results revealed that GTSs improved intestinal microecological disorders and impaired immune function caused by the weightlessness simulation. The underlying mechanism may be related to the \"intestinal immune -microbiota-metabolic\" pathway. These findings provide a theoretical basis for the precise design and development of GTSs for space-health products.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1289-1303"},"PeriodicalIF":4.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Bibliometric and Visual Analysis of Oliceridine Research (2013-2024).","authors":"Cheng Song, Xinxing Huang, Nianping Chen, Qiliang Song, Yuanli Qiu","doi":"10.2147/DDDT.S497186","DOIUrl":"https://doi.org/10.2147/DDDT.S497186","url":null,"abstract":"<p><strong>Purpose: </strong>To explore and analyze the current research progress, hotspots, and future trends in oliceridine research using bibliometric methods.</p><p><strong>Patients and methods: </strong>We searched the Web of Science (WOS) database utilizing the keywords TS = (\"oliceridine*\" OR \"TRV 130*\" OR \"TRV-130*\" OR \"olinvyk*\" OR \"TRV130*\" OR \"C22H31CIN2O2S*\") for relevant research literature on oliceridine from its inception to June 16, 2024. Bibliometric methods were applied, and analysis software such as VOSviewer and CiteSpace were used to visualize the publication timeline, authors, countries and regions, keywords, sources of literature, research hotspots, and co-cited documents related to oliceridine. Co-occurrence and aggregation analyses were conducted, and maps relevant to institutional cooperation were generated.</p><p><strong>Results: </strong>A total of 151 relevant articles were retrieved and included in the final analysis. Most articles were published between 2020 and 2021. The United States has the highest number of publications and citations in this field. Molecular structure development is a pivotal point in this field. Research hotspots were diverse, including acute pain, opioid receptors, β-arrestin, postoperative pain, therapeutic window, respiratory depression, clinical trials, and chronic pain.</p><p><strong>Conclusion: </strong>Oliceridine, a newly developed analgesic, has garnered global interest. The USA is a leading contributor to this field. Recent research has shifted from basic studies to clinical practice.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1305-1321"},"PeriodicalIF":4.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RET Inhibitor SPP86 Is a Potential Candidate for the Clinical Treatment of Cutaneous Melanoma [Letter].","authors":"Yingjian Tan, Rui Li","doi":"10.2147/DDDT.S523115","DOIUrl":"10.2147/DDDT.S523115","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1249-1250"},"PeriodicalIF":4.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Technology Assessment: Evaluation of 8 CGRP-Targeted Therapy Drugs for the Treatment of Migraine.","authors":"Mengyi Li, Siyong Huang, Jiabao Li, Xiao Hu, Jisheng Chen","doi":"10.2147/DDDT.S499848","DOIUrl":"10.2147/DDDT.S499848","url":null,"abstract":"<p><strong>Purpose: </strong>In order to scientifically evaluate the clinical value of the comprehensive attributes of Calcitonin gene-related peptide (CGRP) inhibitor drugs, a comprehensive literature-based clinical evaluation of CGRP-targeted therapy drugs was conducted using the drug evaluation method modified by expert discussion in the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition).</p><p><strong>Methods: </strong>Based on evidence-based data and the relevant elements and weighting in the \"Selection Guidelines\" quantification record form for drug evaluation and selection in medical institutions, adjustments were made according to the characteristics of CGRP-targeted therapy drugs. We systematically evaluated erenumab, galcanezumab, fremanezumab, eptinezumab, rimegepant, ubrogepant, atogepant, zavegepant for safety, efficacy, economy, and pharmacological properties.</p><p><strong>Results: </strong>The final assessment result scores from highest to lowest were rimegepant (84.5 points), erenumab (75.78 points), galcanezumab (74.02 points), fremanezumab (73.93 points), atogepant (72.64 points), eptinezumab (71.69 points), ubrogepant (70.37 points), zavegepant (56.44 points).</p><p><strong>Conclusion: </strong>Rimegepant, erenumab, fremanezumab, atogepant, galcanezumab, eptinezumab, ubrogepant can be entered into the medication list of medical institutions as strongly recommended drugs.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1231-1247"},"PeriodicalIF":4.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomic Analysis, Antiproliferative, Anti-Migratory, and Anti-Invasive Potential of Amlodipine in Lung Cancer Cells.","authors":"Mohammad A Y Alqudah, Mahmoud M Yaseen, Karem H Alzoubi, Belal A Al-Husein, Sanaa K Bardaweel, Ahmad Y Abuhelwa, Ahlam M Semreen, Ruba A Zenati, Raafat El-Awady, Mohd Shara, Yasser Bustanji, Nelson C Soares, Eman Abu-Gharbieh, Wafaa S Ramadan, Mohammad H Semreen","doi":"10.2147/DDDT.S484561","DOIUrl":"10.2147/DDDT.S484561","url":null,"abstract":"<p><strong>Background and objective: </strong>Lung cancer stands as the leading cause of cancer-related fatalities worldwide. While chemotherapy remains a crucial treatment option for managing lung cancer in both early-stage and advanced cases, it is accompanied by significant drawbacks, including severe side effects and the development of chemoresistance. Overcoming chemoresistance represents a considerable challenge in lung cancer treatment. Amlodipine cytotoxicity was previously demonstrated and could make lung cancer cells more susceptible to chemotherapies. This research aims to examine the metabolomics changes that may occur due to amlodipine's anticancer effects on non-small cell lung cancer (NSCLC) cells.</p><p><strong>Methods: </strong>Amlodipine's effects on A549 and H1299 NSCLC were evaluated using a colorimetric MTT assay, a scratch wound-healing assay and Matrigel invasion chambers to measure cell viability, cell migration and cell invasion. Ultra-high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) was used for the untargeted metabolomics investigation.</p><p><strong>Results: </strong>Our study revealed that amlodipine significantly reduced proliferation of cancer cells in a dose-dependent fashion with IC₅₀ values of 23 and 25.66 µM in A549 and H1299 cells, respectively. Furthermore, amlodipine reduced the invasiveness and migration of cancer cells. Metabolomics analysis revealed distinct metabolites to be significantly dysregulated (Citramalic acid, L-Proline, dGMP, L-Glutamic acid, Niacinamide, and L-Acetylcarnitine) in amlodipine-treated cells.</p><p><strong>Conclusion: </strong>The present study illustrates the anticancer effects of amlodipine on lung cancer proliferation, migration, and invasion in vitro and enhance our understanding of how amlodipine exerts its anticancer potential by casting light on these mechanisms.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1215-1229"},"PeriodicalIF":4.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical Research Landscape of Intracranial Nicardipine for Aneurysmal Subarachnoid Hemorrhage: Insights From Bibliometric Analysis.","authors":"Guangtang Chen, Yi Cao, Xiaolin Du, Junshuan Cui, Xi Zeng, Hua Yang, Zeguang Ren, Kaya Xu","doi":"10.2147/DDDT.S503226","DOIUrl":"10.2147/DDDT.S503226","url":null,"abstract":"<p><strong>Background: </strong>The 2023 American Heart Association/American Stroke Association guideline and Wessels et al's 2024 randomized controlled trial highlight the potential benefits of intracranial nicardipine for aneurysmal subarachnoid hemorrhage (aSAH). This study aims to systematically identify the publication trends and research hotspots in this field through bibliometric analysis.</p><p><strong>Methods: </strong>Relevant publications were sourced from the Web of Science Core Collection (WoSCC). Bibliometric and visualization analyses were conducted using the online tools of the WoSCC database and CiteSpace 6.2.R6.</p><p><strong>Results: </strong>Analysis of 28 articles published by 158 researchers from 55 institutions across 8 countries revealed an intermittent small-scale growth in annual publication volume from 1994 to 2024, with a continuous rise in annual citation volume since 2005, indicating growing interest in the field. Japan, Germany, and the United States of America (USA) were the most prolific and influential countries. Institutions such as Tokyo Women's Medical University showed particularly significant contributions. Kasuya Hidetoshi was the most prolific author. There was little global collaboration among countries, institutions, and authors, with distinct regional research characteristics: Japan and Germany focused on intracranial implants, while the USA concentrated on intrathecal injections. Major publishing and co-cited journals included <i>Neurocritical Care, Acta Neurochirurgica, Journal of Neurosurgery</i>, and <i>Stroke</i>. Popular keywords in 2024 included \"preventing cerebral vasospasm\", \"delayed cerebral ischemia\", \"outcome events\", and \"clinical trials\", revealing current research hotspots.</p><p><strong>Conclusion: </strong>This study maps the global clinical research landscape of intracranial application of nicardipine for aSAH from 1994 to 2024, providing valuable references and guidance for future research.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1129-1146"},"PeriodicalIF":4.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medication Safety in Intravenous Therapy: Compatibility of Etoposide with Frequently Drugs Used in Tumour Critical Care During Simulated Y-Site Administration.","authors":"Haiwen Ding, Tong Tong, Sheng Liu, Liqin Tang, Zhaolin Chen","doi":"10.2147/DDDT.S489534","DOIUrl":"10.2147/DDDT.S489534","url":null,"abstract":"<p><strong>Objective: </strong>Etoposide is an antineoplastic agent widely used to treat pediatric and adult cancers. Critically ill patients are expected to receive several intravenous pharmaceutical drugs while admitted to hospitals. When compatibility data are available, intravenous drugs may be administered simultaneously through the Y-site. This study aimed to determine the compatibility of etoposide during simulated Y-site administration with 45 continuous-infusion drugs that are commonly administered in tumor critical care units.</p><p><strong>Methods: </strong>Etoposide was diluted to a concentration of 0.25 mg/mL in 0.9% sodium chloride (NS) and other intravenously tested drugs were reconstituted according to the manufacturer's recommendations to the final clinical desired concentrations. Y-site administration was simulated in vitro by mixing 5 mL etoposide with other diluted intravenous medications under aseptic conditions in a 1:1 ratio. Compatible solutions were withdrawn at certain time intervals (0, 1, 2, 4 hours) after mixing and tested visually, using a Tyndall beam, pH, turbidity, insoluble particles, and UV absorption as measures of compatibility.</p><p><strong>Results: </strong>Etoposide was compatible with 38 (84%) of the 45 drugs tested within four hours. Glutathione and human granulocyte colony-stimulating factor immediately showed incompatibility with etoposide. Within 1 h, four medications (cefuroxime sodium, ilaprazole sodium, mycophenolate, and xuebijing) were incompatible. Within 4 h, one medications (ceftazidime) were also found to be incompatible with etoposide under observation.</p><p><strong>Conclusion: </strong>Seven of the 45 common medications in tumor critical care tested with etoposide were incompatible within 4 h. If co administration is inevitable and the drug is infused through a port catheter, a larger volume of saline (NS) or dextrose 5% in water (D5W) should be used to flush the port catheter before and after the etoposide infusion to clean the lumen of the port catheter.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1147-1161"},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib Monotherapy Versus Lenvatinib in Combination with PD-1 Blockades as Re-Challenging Treatment for Patients with Metastatic Osteosarcoma: A Real-World Study.","authors":"Guohui Song, Qinglian Tang, Jinchang Lu, Huaiyuan Xu, Anqi Wang, Chuangzhong Deng, Hao Wu, Jinxin Hu, Xiaojun Zhu, Jin Wang","doi":"10.2147/DDDT.S501742","DOIUrl":"10.2147/DDDT.S501742","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the efficacy and safety of lenvatinib, either as a monotherapy or in combination with programmed death-1 (PD-1) blockades, as re-challenging treatment in patients with metastatic osteosarcoma following treatment failure with previous tyrosine kinase inhibitors (TKIs).</p><p><strong>Patients and methods: </strong>We retrospectively reviewed the data of 26 patients with metastatic osteosarcoma who received rechallenge treatment with lenvatinib monotherapy or lenvatinib plus PD-1 blockades after failure of the initial TKI treatment from January 2020 to June 2024 in our center. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), and safety.</p><p><strong>Results: </strong>Of the 26 patients, ORR and CBR were 11.5% and 61.5%, respectively. The median duration of follow-up was 15 months (range, 4.3-25.6) with a median PFS of 7.2 months (95% CI: 1.9-12.5). A total of 14 patients received lenvatinib as a monotherapy, and 12 received a combination therapy of lenvatinib and PD-1 blockade. No significant differences were observed in ORR (0 vs 25%) and CBR (57.1 vs 66.7%) between the two groups. Additionally, the combination cohort exhibited a significantly longer PFS compared to the monotherapy cohort (8.6 [95% CI: 5.0-12.1] vs 4.0 months [95% CI: 1.0-7.0], <i>p</i> = 0.022). 96.2% of patients experienced grade 1 or more adverse events (AEs). Grade 3 adverse events occurred in 6 (23.1%) patients. The safety profiles of the lenvatinib and PD-1 blockade combination group were found to be comparable to those of the lenvatinib monotherapy group.</p><p><strong>Conclusion: </strong>Our data indicated that patients with metastatic osteosarcoma could potentially benefit from lenvatinib rechallenge after progress with initial TKI treatment. The combination of lenvatinib and PD-1 blockade therapy demonstrated promising survival outcomes in patients with metastatic osteosarcoma, accompanied by a manageable toxicity profile.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"1119-1128"},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}