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A comparison of the renal function biomarkers serum creatinine, pro-enkephalin and cystatin C to predict clearance of pemetrexed. 比较肾功能生物标志物血清肌酐、原脑啡肽和胱抑素 C,以预测培美曲塞的清除率。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2024-10-04 DOI: 10.1007/s00280-024-04717-w
N de Rouw, R Beunders, O Hartmann, J Schulte, R J Boosman, H J Derijks, D M Burger, M M van den Heuvel, L B Hilbrands, P Pickkers, R Ter Heine
{"title":"A comparison of the renal function biomarkers serum creatinine, pro-enkephalin and cystatin C to predict clearance of pemetrexed.","authors":"N de Rouw, R Beunders, O Hartmann, J Schulte, R J Boosman, H J Derijks, D M Burger, M M van den Heuvel, L B Hilbrands, P Pickkers, R Ter Heine","doi":"10.1007/s00280-024-04717-w","DOIUrl":"https://doi.org/10.1007/s00280-024-04717-w","url":null,"abstract":"<p><strong>Introduction: </strong>For drugs with a narrow therapeutic window, there is a delicate balance between efficacy and toxicity, thus it is pivotal to administer the right dose from the first administration onwards. Exposure of pemetrexed, a cytotoxic drug used in lung cancer treatment, is dictated by kidney function. To facilitate optimized dosing of pemetrexed, accurate prediction of drug clearance is pivotal. Therefore, the aim of this study was to investigate the performance of the kidney function biomarkers serum creatinine, cystatin C and pro-enkephalin in terms of predicting the elimination of pemetrexed.</p><p><strong>Methods: </strong>We performed a population pharmacokinetic analysis using a dataset from two clinical trials containing pharmacokinetic data of pemetrexed and measurements of all three biomarkers. A three-compartment model without covariates was fitted to the data and the obtained individual empirical Bayes estimates for pemetrexed clearance were considered the \"true\" values (Cl<sub>true</sub>). Subsequently, the following algorithms were tested as covariates for pemetrexed clearance: the Chronic Kidney Disease Epidemiology Collaboration equation using creatinine (CKD-EPI<sub>CR</sub>), cystatin C (CKD-EPI<sub>CYS</sub>), a combination of both (CKD-EPI<sub>CR-CYS</sub>), pro-enkephalin as an absolute value or in a combined algorithm with age and serum creatinine, and lastly, a combination of pro-enkephalin with cystatin C.</p><p><strong>Results: </strong>The dataset consisted of 66 subjects with paired observations for all three kidney function biomarkers. Inclusion of CKD-EPI<sub>CR-CYS</sub> as a covariate on pemetrexed clearance resulted in the best model fit, with the largest decrease in objective function (p < 0.00001) and explaining 35% of the total inter-individual variability in clearance. The predictive performance of the model to containing CKD-EPI<sub>CR-CYS</sub> to predict pemetrexed clearance was good with a normalized root mean squared error and mean prediction error of 19.9% and 1.2%, respectively.</p><p><strong>Conclusions: </strong>In conclusion, this study showed that the combined CKD-EPI<sub>CR-CYS</sub> performs best in terms predicting pharmacokinetics of pemetrexed. Despite the hypothesized disadvantages, creatinine remains to be a suitable and readily available marker to predict pemetrexed clearance in clinical practice.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371051","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}
引用次数: 0
Continuous exposure to doxorubicin induces stem cell-like characteristics and plasticity in MDA-MB-231 breast cancer cells identified with the SORE6 reporter. 持续暴露于多柔比星可诱导 MDA-MB-231 乳腺癌细胞的干细胞样特征和可塑性,并通过 SORE6 报告器进行鉴定。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2024-10-01 Epub Date: 2024-08-24 DOI: 10.1007/s00280-024-04701-4
Nohemí Salinas-Jazmín, María Adriana Medina-Mondragón, Jeannie Jiménez-López, Sandra Lucia Guerrero-Rodríguez, Patricia Cuautle-Rodríguez, Marco Antonio Velasco-Velázquez
{"title":"Continuous exposure to doxorubicin induces stem cell-like characteristics and plasticity in MDA-MB-231 breast cancer cells identified with the SORE6 reporter.","authors":"Nohemí Salinas-Jazmín, María Adriana Medina-Mondragón, Jeannie Jiménez-López, Sandra Lucia Guerrero-Rodríguez, Patricia Cuautle-Rodríguez, Marco Antonio Velasco-Velázquez","doi":"10.1007/s00280-024-04701-4","DOIUrl":"10.1007/s00280-024-04701-4","url":null,"abstract":"<p><strong>Purpose: </strong>Cancer stem cells (CSCs) account for recurrence and resistance to breast cancer drugs, rendering them a cause of mortality and therapeutic failure. In this study, we examined the effects of exposure to low concentrations of doxorubicin (Dox) on CSCs and non-CSCs from TNBC.</p><p><strong>Methods: </strong>The effects of Dox were studied using the SORE6 reporter system. We examined the enrichment of the CSCs population, as well as the proliferation, and death of the reporter-positive fraction (GFP + cells) by flow cytometry. The resistant and stemness phenotypes were analyzed by viability and mammosphere formation assay, respectively. We identified differentially expressed and coregulated genes by RNA-seq analysis, and the correlation between gene expression and clinical outcome was evaluated by Kaplan-Mayer analysis using public databases.</p><p><strong>Results: </strong>In MDAMB231 and Hs578t cells, we identified enriched subsets in the CSCs population after continuous exposure to low concentrations of Dox. Cells from these enriched cultures showed resistance to toxic concentrations of Dox and increased efficiency of mammosphere formation. In purified GFP + or GFP- cells, Dox increased the mammosphere-forming efficiency, promoted phenotypic switches in non-CSCs populations to a CSC-like state, reduced proliferation, and induced differential gene expression. We identified several biological processes and molecular functions that partially explain the development of doxorubicin-resistant cells and cellular plasticity. Among the genes that were regulated by Dox exposure, the expression of ITGB1, SNAI1, NOTCH4, STAT5B, RAPGEF3, LAMA2, and GNAI1 was significantly associated with poor survival, the stemness phenotype, and chemoresistance.</p><p><strong>Conclusion: </strong>The generation of chemoresistant cells that have characteristics of CSCs, after exposure to low concentrations of Dox, involves the differential expression of genes that have a clinical impact.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046415","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}
引用次数: 0
Population pharmacokinetic and exposure-toxicity analyses of nab-paclitaxel after pegylated recombinant human granulocyte colony-stimulating factor administration in patients with metastatic breast cancer. 转移性乳腺癌患者服用聚乙二醇重组人粒细胞集落刺激因子后纳布-紫杉醇的群体药代动力学和暴露毒性分析。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.1007/s00280-024-04702-3
Dihong Yang, Gaoqi Xu, Haiying Ding, Like Zhong, Junfeng Zhu, Xiufang Mi, Wenxiu Xin, Tianyan Zhou, Jiaqi Wang, Luo Fang
{"title":"Population pharmacokinetic and exposure-toxicity analyses of nab-paclitaxel after pegylated recombinant human granulocyte colony-stimulating factor administration in patients with metastatic breast cancer.","authors":"Dihong Yang, Gaoqi Xu, Haiying Ding, Like Zhong, Junfeng Zhu, Xiufang Mi, Wenxiu Xin, Tianyan Zhou, Jiaqi Wang, Luo Fang","doi":"10.1007/s00280-024-04702-3","DOIUrl":"10.1007/s00280-024-04702-3","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to establish a population pharmacokinetic (PK) model to evaluate the dynamic relationship between the concentrations of total and unbound paclitaxel, and the exposure-response analysis of albumin-bound paclitaxel (nab-paclitaxel) after pegylated recombinant human granulocyte colony-stimulating factor (PEG-G-CSF) administration in patients with metastatic breast cancer.</p><p><strong>Methods: </strong>A total of 653 concentrations corresponding to total paclitaxel and 334 concentrations corresponding to unbound paclitaxel were analyzed in 24 subjects who randomized received a single 260 mg/m<sup>2</sup> dose of two nab-paclitaxel formulations with a 21-35-day washout period. PEG-G-CSF was administered to all the patients in each cycle to prevent neutropenia. The exposure-response relationships were evaluated using the exposure to total, albumin-coated, and unbound paclitaxel, as well as the reduction in neutrophil count. The exposure data were analyzed using nonlinear mixed-effect modeling. A linear regression model was used to test the statistical significance of the correlation between percentage of reduction in neutrophil count and exposure.</p><p><strong>Results: </strong>The PK characteristics of total paclitaxel were described using a three-compartment model with first-order elimination, and a mechanism-based model incorporating linear release of nab-paclitaxel and the saturated binding of unbound paclitaxel to plasma components was established. The release ratio of paclitaxel from nab-paclitaxel was estimated to be 4.60% and the maximum unbound fraction (2.76%) was reached at the end of the infusion. The study found that a longer duration of total paclitaxel concentration > 0.19 µmol/L was significantly correlated with a reduction in neutrophil count (r<sup>2</sup> = 0.23, P = 0.00062). Specifically, a duration of > 8.6 h was a predictor of a decreased neutrophil count.</p><p><strong>Conclusion: </strong>The decrease in neutrophils induced by nab-paclitaxel was significantly correlated with the duration above a total paclitaxel concentration of 0.19 µmol/L despite the use of PEG-G-CSF.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854939","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}
引用次数: 0
Advancements in physiologically based pharmacokinetic modeling for fedratinib: updating dose guidance in the presence of a dual inhibitor of CYP3A4 and CYP2C19. 费拉替尼生理药代动力学建模的进展:更新CYP3A4和CYP2C19双重抑制剂情况下的剂量指导。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2024-10-01 Epub Date: 2024-08-07 DOI: 10.1007/s00280-024-04696-y
Ming Chang, Yizhe Chen, Ken Ogasawara, Brian James Schmidt, Lu Gaohua
{"title":"Advancements in physiologically based pharmacokinetic modeling for fedratinib: updating dose guidance in the presence of a dual inhibitor of CYP3A4 and CYP2C19.","authors":"Ming Chang, Yizhe Chen, Ken Ogasawara, Brian James Schmidt, Lu Gaohua","doi":"10.1007/s00280-024-04696-y","DOIUrl":"10.1007/s00280-024-04696-y","url":null,"abstract":"<p><strong>Purpose: </strong>A physiologically based pharmacokinetic (PBPK) model for fedratinib was updated and revalidated to bridge a gap between the observed drug-drug interaction (DDI) of a single sub-efficacious dose in healthy participants and the potential DDI in patients with cancer at steady state. The study aimed to establish an appropriate dose for fedratinib in patients coadministered with dual CYP3A4 and CYP2C19 inhibitors, providing quantitative evidence to inform dosing guidance.</p><p><strong>Methods: </strong>The original minimal PBPK model was developed using Simcyp<sup>®</sup> Simulator v17. The model was updated by substituting a single distribution rate (Q<sub>sac</sub>) with 2 separate rates (CL<sub>in</sub>/CL<sub>out</sub>) and transitioning to v20. Model parameter updates were further informed with 3 clinical studies, and 3 more studies served as independent validation data. The validated model was applied to simulate potential DDIs between fedratinib and a known dual inhibitor of CYP3A4 and CYP2C19 (fluconazole).</p><p><strong>Results: </strong>Coadministration of fedratinib with fluconazole in patients was predicted to increase fedratinib exposure by < 2-fold in all simulated scenarios. For patients with cancer receiving the approved dose of fedratinib 400 mg once daily along with fluconazole 200 mg daily, the model predicted an approximate 50% increase in fedratinib exposure at steady state.</p><p><strong>Conclusions: </strong>The updated PBPK model improved description of the observed pharmacokinetics and predicted a low risk of clinically significant DDIs between fedratinib and fluconazole. The quantitative evidence serves as a primary foundation for providing dose guidance in clinical practice for the coadministration of fedratinib with dual CYP3A4 and CYP2C19 inhibitors.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896855","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}
引用次数: 0
Pharmacogenomic associations of cyclophosphamide pharmacokinetic candidate genes with 4hydroxycyclophosphamide formation in children with Cancer. 儿童癌症患者环磷酰胺药代动力学候选基因与 4hydroxycyclophosphamide 形成的药物基因组学关联。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2024-10-01 Epub Date: 2024-07-30 DOI: 10.1007/s00280-024-04703-2
Sandi L Navarro, Navin Pinto, Douglas S Hawkins, Julie R Park, Saam Dilmaghani, Christine Rimorin, Michelle Wurscher, Jeannine S McCune
{"title":"Pharmacogenomic associations of cyclophosphamide pharmacokinetic candidate genes with 4hydroxycyclophosphamide formation in children with Cancer.","authors":"Sandi L Navarro, Navin Pinto, Douglas S Hawkins, Julie R Park, Saam Dilmaghani, Christine Rimorin, Michelle Wurscher, Jeannine S McCune","doi":"10.1007/s00280-024-04703-2","DOIUrl":"10.1007/s00280-024-04703-2","url":null,"abstract":"<p><strong>Purpose: </strong>4-hydroxycyclophosphamide (4HCY) is the principal precursor to the cytotoxic metabolite of cyclophosphamide (CY), which is often used as first-line treatment of children with cancer. There is conflicting data regarding the relationship between CY efficacy, toxicity, and pharmacokinetics with the genes encoding proteins involved in 4HCY pharmacokinetics, specifically its formation and elimination.</p><p><strong>Methods: </strong>We evaluated germline pharmacogenetics in children with various malignancies receiving their first CY dose. Using linear regression, we analyzed the associations between two pharmacokinetic outcomes - how fast a child cleared CY (i.e., CY clearance) and the ratio of the 4HCY/CY exposure, specifically area under the plasma concentration-time curve (AUC), and 372 single nucleotide polymorphisms (SNP) in 14 drug-metabolizing transporters or enzymes involved in 4HCY formation or elimination.</p><p><strong>Results: </strong>Age was associated with the ratio of 4HCY/CY AUC (P = 0.004); Chemotherapy regimen was associated with CY clearance (P = 0.003). No SNPs were associated with CY clearance or the ratio of 4HCY/CY AUC after controlling for a false discovery rate.</p><p><strong>Conclusion: </strong>Age and chemotherapy regimen, but not germline pharmacogenomics, were associated with CY clearance or the ratio of 4HCY/CY AUC. Other methods, such as metabolomics or lipidomics, should be explored.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854938","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}
引用次数: 0
Low serum concentrations of bevacizumab and nivolumab owing to excessive urinary loss in patients with proteinuria: a case series. 蛋白尿患者因尿液流失过多导致贝伐珠单抗和尼伐单抗血清浓度过低:一个病例系列。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2024-10-01 Epub Date: 2024-03-08 DOI: 10.1007/s00280-024-04659-3
Takashi Masuda, Taro Funakoshi, Takahiro Horimatsu, Shinya Yamamoto, Takeshi Matsubara, Sho Masui, Shunsaku Nakagawa, Yasuaki Ikemi, Motoko Yanagita, Manabu Muto, Tomohiro Terada, Atsushi Yonezawa
{"title":"Low serum concentrations of bevacizumab and nivolumab owing to excessive urinary loss in patients with proteinuria: a case series.","authors":"Takashi Masuda, Taro Funakoshi, Takahiro Horimatsu, Shinya Yamamoto, Takeshi Matsubara, Sho Masui, Shunsaku Nakagawa, Yasuaki Ikemi, Motoko Yanagita, Manabu Muto, Tomohiro Terada, Atsushi Yonezawa","doi":"10.1007/s00280-024-04659-3","DOIUrl":"10.1007/s00280-024-04659-3","url":null,"abstract":"<p><strong>Purpose: </strong>Proteinuria can cause interindividual variability in the pharmacokinetics of therapeutic antibodies and may affect therapeutic efficacy. Here, we measured the serum and urinary concentrations of bevacizumab (BV) and nivolumab (NIVO) in patients with proteinuria and reported a case series of these patients.</p><p><strong>Methods: </strong>Thirty-two cancer patients who received BV every 3 weeks or NIVO every 2 weeks between November 2020 and September 2021 at Kyoto University Hospital were enrolled in this study. The serum and urinary concentrations of BV and NIVO were measured using liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>We divided the BV-treated patients and the NIVO-treated patients into two groups based on the urine protein-creatinine ratio (UPCR): UPCR 1 g/g or higher (BV, n = 9; NIVO, n = 3) and UPCR less than 1 g/g (BV, n = 14; NIVO, n = 6). Serum concentrations of the therapeutic antibodies adjusted by their doses were significantly lower in both BV- and NIVO-treated patients with UPCR 1 g/g or higher compared to those with less than 1 g/g. In patients with UPCR 1 g/g or higher, urinary concentrations of the therapeutic antibodies adjusted by their serum concentrations and urinary creatinine concentrations tended to increase.</p><p><strong>Conclusion: </strong>This case-series study suggests a possibility of reduction in serum concentrations of BV and NIVO in patients with proteinuria by urinary excretion of these drugs.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058688","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}
引用次数: 0
Dexamethasone reduces cisplatin-induced hair cell damage by inducing cisplatin resistance through metallothionein-2. 地塞米松通过金属硫蛋白-2诱导顺铂抗性,从而减轻顺铂诱导的毛细胞损伤。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2024-10-01 Epub Date: 2024-08-14 DOI: 10.1007/s00280-024-04706-z
Haruki Ujiie, Naoyuki Nishiya, Ami Yamamoto, Takeru Takada, Megumi Onodera, Ayana Sasaki, Takuya Oikawa
{"title":"Dexamethasone reduces cisplatin-induced hair cell damage by inducing cisplatin resistance through metallothionein-2.","authors":"Haruki Ujiie, Naoyuki Nishiya, Ami Yamamoto, Takeru Takada, Megumi Onodera, Ayana Sasaki, Takuya Oikawa","doi":"10.1007/s00280-024-04706-z","DOIUrl":"10.1007/s00280-024-04706-z","url":null,"abstract":"<p><strong>Purpose: </strong>Hair cell damage is a common side effect caused by the anticancer drug cisplatin (CDDP), which reduces patient quality of life. One CDDP resistance mechanism that occurs in recurrent cancers is heavy metal detoxification by metallothionein-2 (mt2). Here, we show that in zebrafish larvae, dexamethasone (DEX) reduces CDDP-induced hair cell damage by enhancing mt2 expression.</p><p><strong>Methods: </strong>Transgenic zebrafish (cldn: gfp; atoh1: rfp) that express green and red fluorescent proteins in neuromasts and hair cells, respectively, were used. The zebrafish were pretreated with DEX at 52 h post-fertilization (hpf) for 8 h, followed by CDDP treatment for 12 h. The lateral line hair cells of CDDP-treated zebrafish at 72 hpf were observed by fluorescence microscopy.</p><p><strong>Results: </strong>Reporting odds ratio (ROR) analysis using an adverse event database indicated an association between a decrease in CDDP-induced ototoxicity and DEX as an antiemetic treatment for cancer chemotherapy. Pretreatment with DEX protected 72 hpf zebrafish hair cells from CDDP-induced damage. The expression of mt2 mRNA was significantly increased by the combination of 10 µM DEX with CDDP. Gene editing of mt2 reversed the protective effect of DEX against CDDP-induced damage in hair cells.</p><p><strong>Conclusion: </strong>DEX protects hair cells from CDDP-induced damage through increased mt2 expression, which is a resistance mechanism for platinum-based anticancer drugs.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977623","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}
引用次数: 0
The Gustave Roussy Immune score is a powerful biomarker for predicting therapeutic resistance to chemotherapy in gastric cancer patients. 古斯塔夫-鲁西(Gustave Roussy)免疫评分是预测胃癌患者化疗耐药性的有力生物标志物。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2024-10-01 Epub Date: 2024-07-25 DOI: 10.1007/s00280-024-04692-2
Nobuhiro Nakazawa, Makoto Sohda, Mizuki Endo, Nobuhiro Hosoi, Shintaro Uchida, Takayoshi Watanabe, Akihiko Sano, Makoto Sakai, Hiroomi Ogawa, Ken Shirabe, Hiroshi Saeki
{"title":"The Gustave Roussy Immune score is a powerful biomarker for predicting therapeutic resistance to chemotherapy in gastric cancer patients.","authors":"Nobuhiro Nakazawa, Makoto Sohda, Mizuki Endo, Nobuhiro Hosoi, Shintaro Uchida, Takayoshi Watanabe, Akihiko Sano, Makoto Sakai, Hiroomi Ogawa, Ken Shirabe, Hiroshi Saeki","doi":"10.1007/s00280-024-04692-2","DOIUrl":"10.1007/s00280-024-04692-2","url":null,"abstract":"<p><strong>Purpose: </strong>It is highly important to be able to predict the therapeutic efficacy of chemotherapy on patients with unresectable advanced or recurrent gastric cancer (GC). The Gustave Roussy Immune Score (GRIm-s) is a predictor of therapeutic sensitivity to chemotherapy and immune checkpoint inhibitors (ICIs) in other cancers. The present study aimed to analyze the association of the GRIm-s with the therapeutic sensitivity of first-line chemotherapy in GC patients.</p><p><strong>Methods: </strong>We included 156 patients receiving primary chemotherapy treatment for unresectable or advanced recurrent GC between January 2012 and December 2021 at our institution. We evaluated the correlation between the GRIm-s and therapeutic sensitivities to chemotherapy. The GRIm-s was assessed before the start of first-line chemotherapy.</p><p><strong>Results: </strong>Among the 156 patients, 138 (88.5%) and 18 (11.5%) were classified in the low- and high-risk groups, respectively. The GRIm-s high-risk group was significantly older (p = 0.013), had more advanced unresectable cancer (p = 0.0098), and was significantly less likely to progress to second-line chemotherapy (p = 0.014). The overall survival rate (OS) (p = 0.039) and the progression free survival rate (PFS) (p = 0.017) were significantly worse in the GRIm-s high-risk group. The high GRIm-s was an independent prognostic factor for poor survival in multivariate analysis (p = 0.0094).</p><p><strong>Conclusions: </strong>Focusing on the GRIm-s before first-line chemotherapy initiation for unresectable advanced or postoperative recurrent GC was useful in predicting the therapeutic resistance to chemotherapy, transition to second-line chemotherapy, and poor prognosis.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765555","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}
引用次数: 0
Successful use of Palbociclib combined with Venetoclax and Azacitidine in an adult with refractory/relapsed therapy-related acute myeloid leukemia. 成功将 Palbociclib 与 Venetoclax 和阿扎胞苷联合用于一名患有难治性/复发性治疗相关急性髓性白血病的成人患者。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2024-10-01 Epub Date: 2024-03-02 DOI: 10.1007/s00280-024-04642-y
Wenqiang Qu, Jialing Lu, Yujie Ji, Zhewei He, Mengjia Hou, Dongyang Li, Yan Yang, Dan Liu, Suning Chen
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引用次数: 0
Acute kidney injury in a child treated with cisplatin and amphotericin B. 一名接受顺铂和两性霉素 B 治疗的儿童出现急性肾损伤。
IF 2.7 4区 医学
Cancer Chemotherapy and Pharmacology Pub Date : 2024-10-01 Epub Date: 2024-08-07 DOI: 10.1007/s00280-024-04705-0
Torjus Skajaa, Mia Faerch, Henrik Hasle
{"title":"Acute kidney injury in a child treated with cisplatin and amphotericin B.","authors":"Torjus Skajaa, Mia Faerch, Henrik Hasle","doi":"10.1007/s00280-024-04705-0","DOIUrl":"10.1007/s00280-024-04705-0","url":null,"abstract":"<p><p>Cisplatin and amphotericin B are both known to be potentially nephrotoxic. We describe acute kidney injury due to the combination of Liposomal amphotericin B and cisplatin in an adolescent with osteosarcoma. Acute kidney injury (peak creatinine 431 µmol/L) consistent with drug-induced acute tubulointerstitial nephritis was observed a few days after concomitant administration of cisplatin and amphotericin B. Kidney function nearly normalised during follow-up. The timing of the concomitant administration of amphotericin B and cisplatin led us to presume that the combination was the cause of renal failure, and we conclude that concurrent administration of cisplatin and amphotericin B should be avoided.</p>","PeriodicalId":9556,"journal":{"name":"Cancer Chemotherapy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896854","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}
引用次数: 0
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