Cancer Chemotherapy and Pharmacology最新文献

{"title":"Evaluation of Bruton's Tyrosine Kinase (BTK) inhibition with alternative doses of ibrutinib in subjects with Chronic Lymphocytic Leukemia (CLL).","authors":"Aziz Ouerdani, Belén Valenzuela, Nicoline Treijtel, Nahor Haddish-Berhane, Sanjay Desphande, Srimathi Srinivasan, Emma Smith, Juan José Perez Ruixo","doi":"10.1007/s00280-025-04753-0","DOIUrl":"10.1007/s00280-025-04753-0","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate alternative ibrutinib dosing regimens that maintain Bruton's tyrosine kinase (BTK) receptor occupancy over the entire dosing interval for CLL patients using a model-based approach.</p><p><strong>Methods: </strong>Ibrutinib inhibits B-cell proliferation via irreversible binding of BTK. As IC₅₀ is not an appropriate parameter to describe the potency of the inhibition in the presence of a covalent binding inhibitor. A BTK covalent binding model was developed using k_inact/K_I as key parameter to account for covalent binding. The ibrutinib-BTK covalent binding model was used to describe the effect of daily doses of 140, 280, 420 and 560 mg on the proportion of subjects with more than 90% BTK inhibition at steady state trough concentrations. Predictive performance of the model was assessed using the available ibrutinib BTK inhibition data following QD dosing. Model-based predictions were used to identify the minimum ibrutinib QD dose that provides more than 90% inhibition in more than 90% of the subjects.</p><p><strong>Results: </strong>The covalent binding model was able to describe the data and predicted that ibrutinib QD dose reduced from 420 mg to 280 mg or 140 mg may inhibit de novo synthetized BTK efficiently in a CLL population.</p><p><strong>Conclusion: </strong>Using a model-based approach showed that reducing the ibrutinib dosing regimen to 280 mg QD or even 140 mg in case of adverse events could maintain BTK inhibition over the entire dosing interval.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"38"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522662","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":"Population pharmacokinetic modeling of asciminib in support of exposure-response and ethnic sensitivity analyses in patients with chronic myeloid leukemia.","authors":"Christelle Darstein, Deokyong Yoon, Yiqun Yang, Shruti Kapoor, Kohinoor Dasgupta, Shengyuan Wu, Yasunori Kawakita, Matthias Hoch, Kai Grosch, Sherwin K B Sy","doi":"10.1007/s00280-025-04755-y","DOIUrl":"10.1007/s00280-025-04755-y","url":null,"abstract":"<p><strong>Background: </strong>The original population pharmacokinetics (popPK) model for asciminib in patients with chronic myeloid leukemia in chronic phase (CML-CP) was refined to address drug development needs in support of drug submission, namely, attainment of target drug exposure in specific patient populations, populating individual daily exposures for exposure-response analyses of key efficacy and safety endpoints, confirmation of comparability in exposure between 40 mg b.i.d. and 80 mg q.d., and assessment of ethnic insensitivity.</p><p><strong>Methods: </strong>Participants from two organ dysfunction studies, patients with CML in blast and acute phases and acute lymphoblastic leukemia and patients from a phase III efficacy study in newly diagnosed Ph + CML-CP, and data from a dedicated phase II study in the Chinese patients previously treated with at least two prior tyrosine kinase inhibitors, and a phase IIIb study comparing two dose regimens of asciminib (40 mg b.i.d. and 80 mg q.d.) were included in the revised popPK model. Covariates evaluated were line of therapy, baseline renal and hepatic functions, Chinese or Japanese ethnicity.</p><p><strong>Results: </strong>The apparent clearance and steady-state volume of distribution of asciminib were 6.84 L/h and 110 L, respectively, for a typical individual of 70 kg weight and 90 mL/min absolute glomerular filtration rate. Both the 40 mg b.i.d. and 80 mg q.d. resulted in a steady-state daily AUC of 12,600 ng.h/mL, and there was no difference between lines of therapy. Effects of renal or hepatic impairment on clearance were not clinically relevant. Chinese and Japanese exhibited similar PK as that of the global population.</p><p><strong>Conclusions: </strong>The 40 mg b.i.d. and 80 mg q.d. regimens are comparable in their daily exposure, supporting the use of the two dosing regimens in newly diagnosed and previously treated CML-CP patients. The PK of asciminib is insensitive to ethnic differences and no dose adjustment is required for severe renal and hepatic impaired patients.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"39"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522664","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":"Real-world pharmacokinetics of trametinib in pediatric low-grade glioma.","authors":"Laurie Pagnot, Isaline Granger, Jérôme Guitton, Bertrand Favier, Antony Ceraulo, Cécile Faure-Conter, Pierre Leblond, Michael Philippe","doi":"10.1007/s00280-025-04761-0","DOIUrl":"10.1007/s00280-025-04761-0","url":null,"abstract":"<p><strong>Purpose: </strong>Trametinib, a MEK1/2 inhibitor, has emerged as a promising treatment for pediatric patients with low-grade gliomas (LGG). However, trametinib exhibits significant inter-individual pharmacokinetic (PK) variability, and studies in adults demonstrated an exposure-efficacy relationship. This study aimed to evaluate the PK profile of trametinib in pediatric routine care and explore potential exposure-outcome relationships.</p><p><strong>Methods: </strong>We analyzed PK data from 65 blood samples from 19 children receiving trametinib, either as single agent or in combination with dabrafenib. A trough concentration (Cmin) range of 8-15 ng/mL was considered, based on average exposure reported in the largest pediatric study.</p><p><strong>Results: </strong>The mean Cmin was 8.82 ng/ml, with 64.6% of samples falling within the predefined target range, while 35.4% were below it. Regarding tolerance, 84.2% of patients experienced treatment-related toxicities, predominantly skin and subcutaneous tissue disorders. Efficacy data were limited.</p><p><strong>Conclusion: </strong>These findings underscore the necessity of therapeutic drug monitoring in pediatric patients to optimize treatment efficacy and minimize toxicity, highlighting trametinib's potential for personalized dosing strategies in this population.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"35"},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490850","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":"A phase 1 study of the combination of BH3-mimetic, navitoclax, and mTORC1/2 inhibitor, vistusertib, in patients with advanced solid tumors.","authors":"Susan C Scott, Anna Farago, W Victoria Lai, Marianna Zahurak, Michelle A Rudek, Judy Murray, Michael A Carducci, Tamar Uziel, Naoko Takebe, Steven D Gore, Charles M Rudin, Christine L Hann","doi":"10.1007/s00280-025-04760-1","DOIUrl":"10.1007/s00280-025-04760-1","url":null,"abstract":"<p><strong>Purpose: </strong>To determine the, safety, tolerability and recommended phase 2 dosing of the combination of navitoclax, a dual Bcl-2/xL inhibitor, and vistusertib, a TORC1/2 inhibitor.</p><p><strong>Methods: </strong>Patients with advanced solid tumors received navitoclax plus vistusertib following a 3 + 3 dose escalation design. To mitigate thrombocytopenia, a known toxicity of navitoclax, all patients received lead-in dosing of navitoclax alone at 150 mg orally daily for a minimum of 7 days. In addition to safety and tolerability, pharmacokinetics of navitoclax and vistusertib were evaluated.</p><p><strong>Results: </strong>14 patients received combination treatment which was well-tolerated at dose level 1 (navitoclax 150 mg orally daily plus vistusertib 35 mg orally twice daily). The main dose-limiting toxicity, grade 3 serum aminotransferase elevation, occurred in two of five patients at dose level 2 (navitoclax 250 mg orally daily plus vistusertib 35 mg orally twice daily). Navitoclax and vistusertib exposures appeared consistent with levels reported in prior studies of each agent. No responses were observed among the 8 response evaluable patients.</p><p><strong>Conclusions: </strong>A tolerable dose of navitoclax at 150 mg orally daily plus vistusertib at 35 mg orally twice daily was identified in patients with advanced solid tumors and established as the recommended phase 2 dose (RP2D). Further efficacy assessment of this combination, in a planned phase 2 expansion in patients with relapsed small cell lung cancer, was terminated due to discontinuation of vistusertib.</p><p><strong>Trial registration: </strong>NCT03366103 (First posted December 8, 2017).</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"37"},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490848","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":"Model-informed development of a cost-saving dosing regimen for enfortumab vedotin.","authors":"Catharina Jp Op 't Hoog, Amy Rieborn, Dirk Jan Ar Moes, Jeroen Jma Hendrikx, Michiel S van der Heijden, Mira D Franken, Tom van der Hulle, Michel van Kruchten, Annelieke Ecab Willemsen, Stijn Lw Koolen, Emmy Boerrigter, Rob Ter Heine","doi":"10.1007/s00280-025-04764-x","DOIUrl":"10.1007/s00280-025-04764-x","url":null,"abstract":"<p><strong>Aim: </strong>Enfortumab vedotin is an antibody-drug conjugate (ADC) that has been approved for locally advanced or metastatic urothelial cancer, as monotherapy and in combination with pembrolizumab, and has shown significant benefit in progression-free survival and overall survival for these patients. The economic burden of enfortumab vedotin hampers widespread patient access. The aim of this study was to develop a model-informed alternative dosing regimen that results in equivalent drug exposure while reducing the costs and prevent drug spillage.</p><p><strong>Methods: </strong>Population pharmacokinetic modelling was used to simulate a dosing regimen leading to equivalent exposure by using the published population pharmacokinetic model in the registration reports. The alternative dosing regimen was based on weight-bands derived from the established non-linear relationship between body weight and systemic exposure, and the usage of whole vials based on fixed doses to prevent spillage. Equivalent exposure compared to the approved body weight-based dosing regimen was defined as conservative equivalent boundaries of 90-111% for the calculated geometric mean ratios (GMRs) of area under the concentration-time curve and trough concentration.</p><p><strong>Results: </strong>A weight-band based dosing regimen for each dose level of enfortumab vedotin was developed. The GMRs for all pharmacokinetic outcomes were within the predefined equivalence boundaries. In addition, a more even exposure distribution was observed across the body weight quartiles. The average costs savings across all dose levels and per weight-band were approximately 15%.</p><p><strong>Conclusion: </strong>The proposed alternative dosing regimen shows that drug costs and spillage of enfortumab vedotin can be reduced while maintaining an equivalent and more evenly distributed exposure in treated patients.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"36"},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490849","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":"Thymine as potential biomarker to predict 5-FU systemic exposure in patients with gastro-intestinal cancer: a prospective pharmacokinetic study (FUUT-trial).","authors":"Maarten A Hanrath, Evi Banken, Sebastian A H van den Wildenberg, Daan van de Kerkhof, Dirk Jan A R Moes, Michele Boisdron-Celle, Bianca J C van den Bosch, Ramon Bax, Pierre M Bet, Jan Gerard Maring, Geert-Jan M Creemers, Irene E G van Hellemond, Maarten J Deenen","doi":"10.1007/s00280-025-04759-8","DOIUrl":"10.1007/s00280-025-04759-8","url":null,"abstract":"<p><strong>Purpose: </strong>In 20-30% of the patients, fluoropyrimidines (5-FU) based chemotherapy leads to severe toxicity, which is associated with dihydropyridine dehydrogenase (DPD) deficiency. Therefore, DPYD genotyping became standard practice before treatment with fluoropyrimidines. Nevertheless, only 17% of the patients with severe toxicity have a DPYD variant. Therefore, an urgent need persists to investigate other strategies contributing to prediction and prevention of toxicity. Endogenous DPD substrates are considered as potential biomarkers to predict toxicity, yet contradictional data exist on demonstrating uracil as a reliable biomarker. Thymine as biomarker for toxicity has been investigated less. The aim of this study was to determine the association between the concentrations of uracil, thymine dihydrouracil (DHU) and dihydrothymine (DHT), with the systemic drug exposure of 5-FU and DPD enzyme activity in patients treated with 5-FU.</p><p><strong>Methods: </strong>We included 36 patients with gastrointestinal malignancy who received 5-FU infusion. DPYD genotyping was conducted before start of treatment. Blood samples for determining 5-FU, uracil and thymine concentrations during infusion and DPD enzyme activity were taken.</p><p><strong>Results: </strong>We found a significant correlation between the 5-FU systematic exposure and baseline thymine concentrations (R² = 0.1468; p = 0.0402). DPD enzyme activity was significantly correlated with baseline thymine concentrations but no correlation was found between DPD enzyme activity and 5-FU systemic drug exposure.</p><p><strong>Conclusion: </strong>5-FU dose individualization based on thymine concentrations could be a promising addition to DPYD genotyping to predict 5-FU-induced toxicity. Larger prospective trials are needed to examine thymine as predictor for toxicity in daily practice.</p><p><strong>Trial registration: </strong>Trial NL7539 at 'Overview of Medical Research in the Netherlands' (ID NL-OMON21471). Date of registration 19-02-2019.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"34"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425142","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":"Dose adjustment strategy for high-dose methotrexate-induced toxicities in pediatric acute lymphoblastic leukemia: based on population PK analysis and exposure-toxicity relationship.","authors":"Ailing Cao, Yanping Guan, Jian Wang, Xinyu Li, Shu Liu, Qiaolan Xuan, Kunyin Qiu, Yating Zhang, Lvhong Xu, Jianpei Fang, Zhong Zuo, Min Huang, Xueding Wang, Dunhua Zhou","doi":"10.1007/s00280-025-04750-3","DOIUrl":"10.1007/s00280-025-04750-3","url":null,"abstract":"<p><strong>Purpose: </strong>High-dose methotrexate (HD-MTX) is the cornerstone of the therapy for acute lymphoblastic leukemia (ALL). However, severe adverse events are frequently reported despite standard supportive cares. Therefore, we aim to develop a new strategy to individualize HD-MTX and improve patient safety.</p><p><strong>Methods: </strong>A retrospective study was conducted in which toxicity were evaluated in 134 patients with 461 HD-MTX treatment courses. All of the patients experienced standard supportive cares. Exposure-toxicity analysis was conducted to obtain the target concentration and area under the curve (AUC) of MTX. Population PK model was established for dose simulations.</p><p><strong>Results: </strong>A high rate of severe toxicities (78.1%) was observed. Patients with C_24h above 75 µmol/L were at high risk for developing serious myelosuppression (P < 0.001) or hepatic injury (P = 0.005) within each cycle. Moreover, although no effect of AUC_0-24 h was found on toxicities within the relative cycle, a prolonged effect of MTX overexposure was observed on the toxicities in the next cycle. When the AUC_0-24 h levels were above 1447 µmol/L·h, patients were more likely to develop serious myelosuppression (P = 0.004) in the subsequent cycle. Based on the C_24h and AUC_0-24 h levels and the known required effective doses, reducing the dose from 5 g/m² to 2-3 g/m² according to the risk stratification is recommended to prevent related toxicities.</p><p><strong>Conclusion: </strong>MTX C_24h and AUC_0-24 h levels are the predictors of HD-MTX-related toxicity. For patients with overdose of HD-MTX, a new dose adjustment strategy is established to improve patient safety and optimize clinical benefit.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"33"},"PeriodicalIF":2.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425139","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 approach to busulfan dosing in infants and children based on a population pharmacokinetic analysis.","authors":"Frank M Balis, Elizabeth Rieger, Nancy J Bunin, JoAnn Gardiner, Leslie M Shaw, Timothy S Olson, Michael C Milone","doi":"10.1007/s00280-025-04757-w","DOIUrl":"10.1007/s00280-025-04757-w","url":null,"abstract":"<p><strong>Purpose: </strong>Apply population pharmacokinetic modeling to a single institution busulfan therapeutic drug monitoring (TDM) data set from infants and children to refine dosing methods.</p><p><strong>Methods: </strong>One-compartment pharmacokinetic model was fit to busulfan TDM data from 328 infants and children with malignant and non-malignant diseases treated with busulfan-containing transplant conditioning regimens. Age-dependence of busulfan clearance scaled to body weight and body surface area (BSA) was compared, and busulfan AUC was simulated for a BSA-scaled dose of 100 mg/m² combined with a BSA-banded dosing table for infants and children with a BSA < 0.5 m².</p><p><strong>Results: </strong>Busulfan clearance scaled to body weight is age-dependent. Clearance in children ≤ 3 years (0.234 L/[h•kg]) is higher than the typical value for the population, (0.205 L/[h•kg]), and 48% of children < 5 years have subtherapeutic busulfan AUCs after the first dose. Busulfan clearance scaled to BSA (typical value, 5.47 L/[h•m²]) is more uniform across the pediatric age span, except for infants (≤ 1 year, 4.27 L/[h•m²]). Simulated busulfan AUCs with a dose of 100 mg/m² for patients with a BSA ≥ 0.5 m² combined with a BSA-banded dosing table for patients with a BSA < 0.5 m² achieved a therapeutic AUC after the first dose in 49% more patients than body weight scaled doses.</p><p><strong>Conclusion: </strong>Our model predicts a greater proportion of children would achieve a therapeutic busulfan AUC after the first dose with a dose of 100 mg/m²/d combined with the infant dosing table for patients with a BSA < 0.5 m² compared to body weight-scaled dosing.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"32"},"PeriodicalIF":2.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390196","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":"Food effect trial of the pharmacokinetics and safety of TQ05105 in healthy Chinese subjects.","authors":"Jun Dai, Yang Cheng, Yannan Zhou, Yanli Wang, Zhengzhi Liu, Qing Ren, Zhengjie Su, Qiaohuan Deng, Haimiao Yang, Yingzi Cui","doi":"10.1007/s00280-025-04754-z","DOIUrl":"10.1007/s00280-025-04754-z","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate the effect of food intake on the pharmacokinetics of TQ05105 tablets in healthy Chinese subjects, and to evaluate the safety in these subjects.</p><p><strong>Methods: </strong>This Phase I clinical trial involved healthy subjects who received a single oral dose of 15 mg TQ05105, with a 2-day washout period between each period. The plasma concentrations of TQ05105 and its metabolite TQ12550 were quantified using a validated liquid chromatography-tandem mass spectrometry method. Safety assessments were conducted throughout the study.</p><p><strong>Results: </strong>The study enrolled 16 healthy Chinese subjects (10 males and 6 females). Compared with the fasting condition, the postprandial administration of TQ05105 resulted in significant reductions in the maximum concentration (C_max) and area under the curve (AUC) of both TQ05105 and its metabolite TQ12550. Additionally, both the time to peak concentration (T_max) and half-life (t_1/2) of TQ05105 and its metabolite were prolonged under postprandial conditions. No serious adverse events were reported during the study.</p><p><strong>Conclusion: </strong>The findings demonstrate that food intake significantly alters the pharmacokinetic parameters of TQ05105 and its metabolite TQ12550, with a notable decrease in C_max and AUC, and an increase in T_max and t_1/2. The single dose of the drug was well tolerated.</p><p><strong>Registration information: </strong>This trial had registered at the Clinical Trials.gov on August 08, 2023 ( https://clinicaltrials.gov , NCT05982106).</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"31"},"PeriodicalIF":2.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381692","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":"Retraction Note: Long noncoding RNA GAS5 inhibits malignant proliferation and chemotherapy resistance to doxorubicin in bladder transitional cell carcinoma.","authors":"Hui Zhang, Yan Guo, Yongsheng Song, Chao Shang","doi":"10.1007/s00280-025-04758-9","DOIUrl":"https://doi.org/10.1007/s00280-025-04758-9","url":null,"abstract":"","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":"95 1","pages":"30"},"PeriodicalIF":2.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078780","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}