Cancer Chemotherapy and Pharmacology最新文献

{"title":"Synergistic anti-tumor activity of andrographolide and gemcitabine in intrahepatic cholangiocarcinoma through inhibition of RRM2 and the JAK/STAT3 pathway.","authors":"Qinghang Song, Chunjuan Yu, Fulin Sun, Wenbo Wang, Ziyuan Wen, Ruolan Chen, Yiming Wang, Haoran Wang, Zhenxiang Wang, Bing Li, Lina Yang","doi":"10.1007/s00280-026-04897-7","DOIUrl":"10.1007/s00280-026-04897-7","url":null,"abstract":"<p><strong>Purpose: </strong>Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy frequently characterized by intrinsic resistance to standard gemcitabine (Gem) chemotherapy. This study aimed to investigate whether andrographolide (Andro) could sensitize intrinsically gemcitabine-resistant ICC cells to gemcitabine and to explore the underlying molecular mechanisms.</p><p><strong>Methods: </strong>Naturally Gem-resistant ICC cell lines (HUCCT-1 and QBC-939) were treated with Andro, Gem, or their combination. Synergistic effects were quantified using the Chou-Talalay method. Anti-tumor efficacy was assessed via CCK-8, colony formation, EdU incorporation, wound healing, and Transwell invasion assays. ROS accumulation, apoptosis, mitochondrial membrane potential, and cell-cycle distribution were assessed by fluorescence microscopy and flow cytometry, as appropriate. Molecular targets were identified using molecular docking, RT-qPCR, and Western blotting.</p><p><strong>Results: </strong>Andro and Gem exhibited strong synergistic anti-tumor activity (Combination Index < 1.0) in both cell lines. The combination significantly suppressed proliferation, motility, and epithelial-mesenchymal transition. Mechanistically, the synergy was driven by a surge in intracellular ROS, triggering mitochondrial apoptosis and G1/S phase arrest. Furthermore, Ribonucleotide-diphosphate reductase subunit M2 was identified as a candidate molecular target associated with the effects of andrographolide, leading to its downregulation and the subsequent inactivation of the JAK/STAT3 signaling pathway.</p><p><strong>Conclusion: </strong>Andrographolide overcomes intrinsic Gem resistance in ICC, potentially through modulation of the RRM2/JAK/STAT3 axis. This combination therapy represents a promising strategy for treating chemoresistant intrahepatic cholangiocarcinoma.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866968","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":"Glucarpidase efficacy in mitigating methotrexate toxicity is unaffected by concurrent administration of folinic acid.","authors":"Martin Wahlestedt, Karin Hansson, Alexandra Bill, Anders Isaksson, Jesper Heldrup, Cornelis Jan Pronk","doi":"10.1007/s00280-026-04880-2","DOIUrl":"10.1007/s00280-026-04880-2","url":null,"abstract":"<p><strong>Purpose: </strong>High-dose methotrexate (HDMTX) is a cornerstone in pediatric oncology, but delayed methotrexate elimination (DME) can cause severe toxicity. Rescue therapy typically combines folinic acid (FA) and glucarpidase (GP), yet current guidelines recommend pausing FA around GP administration due to presumed interference. This study aimed to determine whether FA affects GP efficacy in metabolizing methotrexate and to assess the impact on folate metabolites.</p><p><strong>Methods: </strong>An ex vivo model was developed using human plasma spiked with clinically relevant concentrations of methotrexate and FA, with or without GP. Samples were analyzed by mass spectrometry to quantify methotrexate, FA, and related metabolites. Additional experiments included blood from pediatric patients receiving HDMTX per ALLTogether protocol.</p><p><strong>Results: </strong>GP rapidly metabolized > 99% of methotrexate across all tested conditions, regardless of FA presence, producing robust DAMPA levels. FA degradation by GP was observed at varying levels, ranging from 8 to 78%. Patient samples confirmed efficient methotrexate clearance by GP, with similar DAMPA production whether FA was present or absent.</p><p><strong>Conclusion: </strong>Concurrent FA administration does not compromise GP efficacy in neutralizing methotrexate. These findings challenge current recommendations to suspend FA around GP dosing and suggest that continuous FA rescue may be safe and beneficial. Adjustments to FA dosing post-GP may be warranted due to partial FA degradation. Further clinical studies should refine rescue strategies to optimize efficacy and minimize toxicity.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834171","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":"The CetuxIMAX study: a population pharmacokinetic approach to modelling the pharmacokinetics and pharmacodynamics relationships of Cetuximab in patients with head and neck cancer.","authors":"Clémence Marin, Anthéa Deschamps, Quentin Gerbault, Clémence Toullec, Florian Clatot, Maureen Bernadach, Jérôme Fayette, Amaury Daste, Philippe Ceruse, Mickael Burgy, Cédric Champetier, Cyril Abdeddaim, Esma Saada-Bouzid, Xavier Tchiknavorian, Sylvie Zanetta, Pascal Auquier, Joseph Ciccolini, Sébastien Salas","doi":"10.1007/s00280-026-04892-y","DOIUrl":"10.1007/s00280-026-04892-y","url":null,"abstract":"<p><p>Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor (EGFR) and is used to treat head and neck squamous cell carcinoma (HNSCC). Despite its clinical benefits, significant interindividual variability in efficacy and toxicity has been observed, which could be at least partly due to differences in pharmacokinetics. The CetuxIMAX study aimed to evaluate the predictive value of Cetuximab exposure levels for disease control (i.e., composite criteria including complete and partial response and stable disease). CetuxIMAX was a prospective, non-interventional, single-arm, multicenter study conducted in patients with HNSCC who were receiving Cetuximab. Plasma concentrations were measured and pharmacokinetic (PK) metrics and parameters were modelled using a two-compartment structure with linear and saturable elimination. Covariate analysis included BSA, age, and serum albumin. Significant variability in Cetuximab plasma concentrations was observed between patients (i.e., > 40%). A trough concentration threshold of 38 µg/mL was identified as predictive of disease control, aligning with prior findings, although final multivariate analysis found that skin toxicity only was associated with efficacy endpoints. However, protocol-specific thresholds varied, with upper values observed in the EXTREME and CaX protocols (i.e., cetuximab in association with cisplatin with or without 5-fluorouracil). No significant PK-toxicity relationships were found. The final PK model demonstrated robustness, with BSA and albumin influencing volume of distribution parameters. The CetuxIMAX study seems to confirm the predictive value of early Cetuximab plasma levels for disease control, but not for long-term survival or safety endpoints.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763220","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":"Evaluation of QTc interval prolongation in patients with advanced clear cell renal cell carcinoma treated with first line sunitinib.","authors":"Agata Sałek-Zań, Mirosława Püsküllüoğlu, Agnieszka Stąpór, Justyna Jaworska, Agnieszka Pietruszka, Aleksandra Grela-Wojewoda, Maciej Stąpór, Tomasz Banaś","doi":"10.1007/s00280-026-04884-y","DOIUrl":"10.1007/s00280-026-04884-y","url":null,"abstract":"<p><p>BACKGROUND: Sunitinib, a multitargeted tyrosine kinase inhibitor, is used in advanced clear cell renal cell carcinoma (ccRCC). Corrected QT interval (QTc) prolongation is a recognized cardiovascular toxicity of this therapy. AIM: To evaluate the incidence, timing, and severity of QTc prolongation in real-world advanced ccRCC patients treated with first-line sunitinib, compare Bazett’s and Fridericia’s correction formulas, and identify risk factors. MATERIALS AND METHODS: This retrospective single-center cohort study included 67 patients between January 2019 and June 2022. QTc was calculated manually using Bazett’s and Fridericia’s formulas and graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The incidence, timing, and severity of QTc prolongation were assessed based on the highest recorded QTc value. Statistical analyses compared QTc values between formulas and evaluated potential clinical predictors of QTc prolongation. RESULTS: The median treatment duration was 1.4 years (IQR 0.72–2.99). QTc prolongation ≥ 450ms occurred in 44.8% of patients (Bazett) and 34.3% (Fridericia) and ≥ 500ms in 7 and 6 patients, respectively. The median onset of QTc ≥ 450ms was cycle 7.9 (Bazett) and 10.4 (Fridericia). Bazett’s values were significantly higher across most treatment cycles (p < 0.05). Older age, thyroid dysfunction, smoking history, hypertension and soft-tissue metastases were associated with increased risk of QTc prolongation. CONCLUSIONS: QTc prolongation was frequent and occurred both early and later during therapy. Fridericia’s formula provided more accurate and stable values and should be preferred for monitoring. Repeated ECG measurements and close cardio-oncology collaboration are essential. </p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763238","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":"Repurposing artesunate in acute myeloid leukemia: a pharmacokinetic rationale derived from antimalarial data.","authors":"Woei Jye Ong","doi":"10.1007/s00280-026-04881-1","DOIUrl":"10.1007/s00280-026-04881-1","url":null,"abstract":"<p><p>BACKGROUND: Artesunate (AS), a standard antimalarial, is a promising candidate for repurposing in Acute Myeloid Leukemia (AML) due to its ability to induce iron-dependent ferroptosis and apoptosis. However, a pharmacokinetic (PK) mismatch exists: while antimalarial dosing focuses on rapid parasite clearance via high-concentration peaks, AML cytotoxicity requires sustained exposure to the active metabolite, dihydroartemisinin (DHA). Currently, standard bolus dosing leads to rapid clearance (DHA t½ ≈ 1–2 h), creating a pharmacokinetic mismatch for oncology applications.Purpose: To develop a pharmacokinetic rationale for repurposing artesunate by defining an exposure-time framework that aligns its known pharmacology with the requirements for sustained cytotoxicity in AML. METHODS: A pharmacokinetic model was developed for a 70 kg adult using published human data. The model integrated the rapid conversion of AS to DHA (f_conv = 0.9), respective volumes of distribution, and elimination rates(k_DHA = 0.462 h⁻¹). Three dosing strategies were simulated: intermittent bolus, a 6-hour infusion, and a 24-hour infusion. Exposure targets were anchored to a known Phase I Maximum Tolerated Dose (MTD) of 18 mg/kg. RESULTS: Simulations demonstrated that intermittent bolus dosing produces high, transient peaks (~11 µg/mL) followed by rapid sub-therapeutic troughs. In contrast, a 24-hour infusion (or a loading dose of 4.5 mg/kg followed by a 9 mg/kg maintenance infusion) achieved a stable DHA plateau within the ideal cytotoxic range of 0.5 - 1.5 µg/mL (≈1.6–4.8 µM) . Even when constrained by the aqueous instability of artesunate (10–12 hours), the model showed that segmented infusions could effectively maintain the required time-above-threshold. CONCLUSION: This study provides a pharmacokinetic rationale for transitioning from bolus to prolonged infusion strategies in AML. By reshaping the exposure profile to maintain steady low-micromolar DHA levels, artesunate can be optimized to trigger the oxidative and ferroptotic pathways necessary for antileukemic efficacy while remaining within established safety boundaries. </p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763202","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":"Pharmacokinetics of venetoclax in a patient after whipple pancreaticoduodenectomy.","authors":"Tien V Le, Allison Dunn, Julianne L Holleran, Christinea Marino, Angela Burrie, Ashkan Emadi, Jan H Beumer","doi":"10.1007/s00280-026-04895-9","DOIUrl":"10.1007/s00280-026-04895-9","url":null,"abstract":"<p><p>The impact of Whipple Pancreaticoduodenectomy, which involves the resection of the duodenum and partial stomach, on the pharmacokinetic (PK) of venetoclax, is unknown. This case reported the PK parameters of venetoclax in a patient with synchronous acute myeloid leukemia and pancreatic ductal adenocarcinoma, who underwent a Whipple procedure, and was treated with a single dose of venetoclax 400 mg. Due to the limited sampling available, the PK parameters of venetoclax in this patient could not be determined by noncompartmental analysis. We leveraged the existing population pharmacokinetic (POP-PK) model to predict this patient’s concentration–time profile and PK parameters from sparse observed data post hoc. The model-predicted concentration resulted in adequate reconstruction of the patient’s concentration-time profile. Our patient Cmax was approximately 234 µg/L, 5-fold below the Cmax of 1050 µg/L-1077 µg/L as reported for the general population. Despite the expected decrease in systemic exposure due to the Whipple, our patient AUC0-∞ was 20.4 mg*h/L (modeled out to infinity) or 15.4 mg*h/L (absorption truncated at 48 hour), approximately 2-fold below the mean AUC values reported in the literature of 32.8 (±16.9), and 24.3 (1.5 geoSD) mg*h/L, yet well within the population range of values. Overall, Whipple leads to a significant change in the PK characteristics of venetoclax. Change in dosing strategy in patients with a similar clinical profile in order to achieve venetoclax concentrations comparable to the reference population at a single dose of 400 mg is recommended. </p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763193","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":"Deciphering autophagy-metabolism interactions in cancer drug resistance: a comprehensive review.","authors":"Mohanprasanth Aruchamy, Snega Ramanathan, Nandhini Shanmugam, Saravanan Muthupandian","doi":"10.1007/s00280-026-04894-w","DOIUrl":"10.1007/s00280-026-04894-w","url":null,"abstract":"<p><p>Drug resistance is a formidable obstacle in the treatment of various cancers, significantly undermining the efficacy of therapeutic interventions and posing a substantial challenge to achieving optimal clinical outcomes. Emerging research has highlighted the critical role of the interplay between autophagy and cellular metabolism in driving drug resistance. Autophagy, a cellular recycling process, and metabolic reprogramming, which involves alterations in cellular metabolic pathways, collectively enable cancer cells to survive and proliferate despite therapeutic stress. This comprehensive review aims to elucidate the mechanisms by which autophagy and metabolism interact to confer drug resistance in cancer cells. We explore how autophagy supports cancer cell survival by recycling nutrients and maintaining cellular homeostasis under stress. Furthermore, we discuss about metabolic reprogramming, specifically enhanced glycolysis, oxidative phosphorylation, and fatty acid metabolism, and how these metabolic shifts contribute to the development of drug resistance.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763230","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":"High-dose methotrexate toxicokinetic variability persists despite standardized 24-hour infusion in childhood ALL.","authors":"Ioannis Kyriakidis, Georgios Monastiriotis, Nikolaos Katzilakis, Iordanis Pelagiadis, Eftichia Stiakaki","doi":"10.1007/s00280-026-04890-0","DOIUrl":"https://doi.org/10.1007/s00280-026-04890-0","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763210","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":"Homoharringtonine suppresses gastric cancer progression by targeting PI3K/ AKT/FOXO pathway and impairing the GSH-GPX4 antioxidant axis.","authors":"Xiaonan Wang, Xiao Ying, Sunyuan Lv, Shanshan Ru, Haonan Jin, Yingzhe Zhang, Jingjing Guo","doi":"10.1007/s00280-026-04893-x","DOIUrl":"10.1007/s00280-026-04893-x","url":null,"abstract":"<p><p>PURPOSE: To investigate the unexplored therapeutic potential and identify the specific molecular targets of homoharringtonine (HHT) in gastric cancer (GC). METHODS: HHT’s efficacy was evaluated in GC cell lines (MKN1/MKN45), normal epithelial cells (GES-1), and an HGC27 xenograft model. Mechanisms were investigated using RNA-sequencing, microscale thermophoresis (MST), molecular docking, and biochemical assays. RESULTS: HHT suppressed GC cell proliferation and migration, inducing G1-phase arrest and apoptosis, while demonstrating lower cytotoxicity toward normal GES-1 cells. MST and docking assays confirmed that HHT directly and stably binds to AKT (KD= 6.496 nM) and suppresses the PI3K/AKT/FOXO/GSK3β signaling pathway. Concurrently, transcriptomic profiling and experimental validation showed that HHT disrupts glutathione metabolism. It depleted intracellular GSH and downregulated GPX4, triggering ferroptosis-like oxidative damage and mitochondrial cristae loss. In vivo, HHT inhibited GC xenograft tumor growth without causing systemic toxicity, which was accompanied by decreased Ki-67 and increased Caspase-3 expression. CONCLUSION: HHT inhibits GC progression by suppressing AKT-mediated tumor growth and inducing GPX4-dependent ferroptosis. These findings highlight HHT as a promising targeted therapeutic for GC. </p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763160","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":"Does mifamurtide affect the elimination of high-dose methotrexate in children with osteosarcoma?","authors":"Maayan Antebi, Laila Nassar, Daniel Kurnik, Oz Mordechai","doi":"10.1007/s00280-026-04883-z","DOIUrl":"10.1007/s00280-026-04883-z","url":null,"abstract":"<p><p>BACKGROUND: The standard treatment protocol for osteosarcoma in children and adolescents includes neoadjuvant (pre-surgical) MAP chemotherapy (high-dose methotrexate [HD-MTX], high-dose doxorubicin, and cisplatin), full resection of the tumor, and then adjuvant post-surgical chemotherapy. In Europe, the immunostimulant mifamurtide is often added to the post-surgical MAP courses in patients with non-metastatic disease, based on evidence that it increases 6-year overall survival. It is unknown whether mifamurtide affects the elimination of HD-MTX. METHODS: In a retrospective single-center study, we reviewed clinical and laboratory parameters of children and adolescents with osteosarcoma who received the MAP protocol between 2012 and 2020. Patients were classified into two cohorts based on post-operative treatment exposure: an “HD-MTX + mifamurtide cohort” (patients with localized disease received pre-operatively HD-MTX and postoperatively HD-MTX with mifamurtide) and an “HD-MTX only” cohort (patients with metastatic disease received only HD-MTX pre- and post-operatively). For each HD-MTX dose, we calculated the area under the concentration curve (AUC24−72) from MTX plasma concentrations collected 24, 48, and 72 h after the beginning of the HD-MTX infusion. We compared AUC24−72 for HD-MTX doses before and after surgery in both cohorts. RESULTS: Among 21 patients (mean age 16; 38% female), 11 were in the “HD-MTX + mifamurtide cohort”, and 10 in the “HD-MTX only” cohort. Among patients in the “HD-MTX + mifamurtide cohort”, the median MTX AUC24−72 in cycles before surgery (67.6 µmol*h/L; interquartile range, 51.2-131.4 µmol*h/L) was not significantly different from that in cycles after surgery with concomitant mifamurtide (84.5 µmol*h/L; IQR, 50.2-155.8 µmol*h/L; P = 0.61). Similarly, in patients in the “HD-MTX only” cohort, median AUC24−72 before and after surgery were comparable (P = 0.70).ConclusionsConcomitant mifamurtide therapy does not have a significant effect on methotrexate elimination after HD-MTX in children with osteosarcoma </p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"96 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716046","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}